Tricyclic oxazolidinone antibiotic compounds

Abstract

The invention relates to compounds of formula I ##STR00001##
wherein custom character is a bond or is absent, V is CH, CR.sup.6 or N; R.sup.0 is H or, if is a bond, may also be alkoxy; R.sup.1 is H or halogen; U is CH or N when is a bond, or, if is absent, U is CH.sub.2, NH or NR.sup.9; R.sup.2 is H, alkylcarbonyl or —CH.sub.2—R.sup.3; R.sup.3 is H, alkyl or hydroxyalkyl; R.sup.4 is H or, if n is not 0 and R.sup.5 is H, may also be OH; R.sup.5 is H, alkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, carboxy or alkoxycarbonyl; R.sup.6 is hydroxyalkyl, carboxy, alkoxycarbonyl or —(CH.sub.2).sub.q—NR.sup.7R.sup.8, q being 1, 2 or 3 and each of R.sup.7 and R.sup.8 independently being H or alkyl or R.sup.7 and R.sup.8 forming with the N atom bearing them a ring; R.sup.9 is alkyl or hydroxyalkyl; A is —(CH.sub.2).sub.p—, —CH.sub.2CH.sub.2CH(OH)— or —COCH.sub.2CH(OH)—; G is substituted phenyl or G.sup.1 or G.sup.2 ##STR00002##
wherein Q is O or S and X is CH or N; and Y.sup.1, Y.sup.2 and Y.sup.3 may each be CH or N; and n is 0 when A is —CH.sub.2CH.sub.2CH(OH)— or —COCH.sub.2CH(OH)—, and n is 0, 1 or 2 when A is —(CH.sub.2).sub.p—, p being 1, 2, 3 or 4, with the proviso that the sum of n and p is then 2, 3 or 4; and to salts thereof.

Claims

1. A compound of formula I ##STR00082## wherein “- - - - -” is a bond or is absent; R.sup.0 represents H or, in the case “- - - - -” is a bond, may also represent (C.sub.1-C.sub.3)alkoxy; R.sup.1 represents H or halogen; U represents CH or N when “- - - - -” is a bond, or, in case “- - - - -” is absent, U represents CH.sub.2, NH or NR.sup.9; V represents CH, CR.sup.6 or N; R.sup.2 represents H, (C.sub.1-C.sub.3)alkylcarbonyl or a group of the formula CH.sub.2—R.sup.3; R.sup.3 represents H, (C.sub.1-C.sub.3)alkyl or (C.sub.1-C.sub.3)hydroxyalkyl; R.sup.4 represents H or, in the cases wherein n is not 0 and R.sup.5 is H, may also represent OH; R.sup.5 represents H, (C.sub.1-C.sub.3)alkyl, (C.sub.1-C.sub.3)hydroxyalkyl, (C.sub.1-C.sub.3)aminoalkyl, (C.sub.1-C.sub.3)alkoxy(C.sub.1-C.sub.3)alkyl, carboxy or (C.sub.1-C.sub.3)alkoxycarbonyl; R.sup.6 represents (C.sub.1-C.sub.3)hydroxyalkyl, carboxy, (C.sub.1-C.sub.3)alkoxycarbonyl or a group —(CH.sub.2).sub.q—NR.sup.7R.sup.8 wherein q is 1, 2 or 3 and each of R.sup.7 and R.sup.8 independently represents H or (C.sub.1-C.sub.3)alkyl or R.sup.7 and R.sup.8 form together with the nitrogen atom bearing them a pyrrolidinyl, piperidinyl, morpholinyl or thiomorpholinyl ring; R.sup.9 represents (C.sub.1-C.sub.3)alkyl, 2-hydroxy-ethyl, 2-hydroxy-propyl or 3-hydroxy-propyl; A represents —(CH.sub.2).sub.p—, —CH.sub.2CH.sub.2CH(OH)— or —COCH.sub.2CH(OH)—; G represents a phenyl group which is substituted once or twice in the meta and/or para position(s) by substituents selected independently from (C.sub.1-C.sub.4)alkyl, (C.sub.1-C.sub.3)alkoxy and a halogen, or G is a group having one of the formulae G.sup.1 and G.sup.2 below ##STR00083## wherein Q is O or S and X is CH or N; and Y.sup.1, Y.sup.2 and Y.sup.3 each represent CH, or Y.sup.1 and Y.sup.3 each represent CH and Y.sup.2 represents N, or Y.sup.1 represents N, Y.sup.2 represents CH or N and Y.sup.3 represents CH, or Y.sup.1 and Y.sup.2 each represent CH and Y.sup.3 represents N; and n is 0 when A represents —CH.sub.2CH.sub.2CH(OH)— or —COCH.sub.2CH(OH)—, and n is 0, 1 or 2 when A represents (CH.sub.2).sub.p, p being 1, 2, 3 or 4, with the proviso that the sum of n and p is then 2, 3 or 4; or a salt of such a compound.

2. The compound of formula I according to claim 1, which is also a compound of formula I.sub.P3 ##STR00084## wherein “- - - - -” is a bond or is absent; R.sup.0 represents H or, in the case “- - - - -” is a bond, may also represent (C.sub.1-C.sub.3)alkoxy; R.sup.1 represents H or halogen; U represents CH or N when “- - - - -” is a bond, or, in case “- - - - -” is absent, U represents CH.sub.2 or NH; V represents CH, CR.sup.6 or N; R.sup.2 represents H, (C.sub.1-C.sub.3)alkylcarbonyl or a group of the formula —CH.sub.2—R.sup.3; R.sup.3 represents H, (C.sub.1-C.sub.3)alkyl or (C.sub.1-C.sub.3)hydroxyalkyl; R.sup.4 represents H or, in the cases wherein n is not 0 and R.sup.5 is H, may also represent OH; R.sup.5 represents H, (C.sub.1-C.sub.3)alkyl, (C.sub.1-C.sub.3)hydroxyalkyl, (C.sub.1-C.sub.3)alkoxy(C.sub.1-C.sub.3)alkyl or (C.sub.1-C.sub.3)alkoxycarbonyl; R.sup.6 represents (C.sub.1-C.sub.3)hydroxyalkyl, carboxy, (C.sub.1-C.sub.3)alkoxycarbonyl or a group —(CH.sub.2).sub.q—NR.sup.7R.sup.8 wherein q is 1, 2 or 3 and each of R.sup.7 and R.sup.8 independently represents H or (C.sub.1-C.sub.3)alkyl or R.sup.7 and R.sup.8 form together with the nitrogen atom bearing them a pyrrolidinyl, piperidinyl, morpholinyl or thiomorpholinyl ring; A represents —(CH.sub.2).sub.p—, —CH.sub.2CH.sub.2CH(OH)— or —COCH.sub.2CH(OH)—; G represents a phenyl group which is substituted once or twice in the meta and/or para position(s) by substituents selected independently from (C.sub.1-C.sub.4)alkyl, (C.sub.1-C.sub.3)alkoxy and a halogen, or G is a group having one of the formulae G.sup.1 and G.sup.2 below ##STR00085## wherein Q is O or S and X is CH or N; and Y.sup.1, Y.sup.2 and Y.sup.3 each represent CH, or Y.sup.1 and Y.sup.3 each represent CH and Y.sup.2 represents N, or Y.sup.1 represents N, Y.sup.2 represents CH or N and Y.sup.3 represents CH, or Y.sup.1 and Y.sup.2 each represent CH and Y.sup.3 represents N; and n is 0 when A represents —CH.sub.2CH.sub.2CH(OH)— or —COCH.sub.2CH(OH)—, and n is 0, 1 or 2 when A represents (CH.sub.2).sub.p, p being 1, 2, 3 or 4, with the proviso that the sum of n and p is then 2, 3 or 4; or a salt of such a compound.

3. The compound of formula I according to claim 1, which is also a compound of formula I.sub.P2 ##STR00086## wherein “- - - - -” is a bond or is absent; R.sup.0 represents H or, in the case “- - - - -” is a bond, may also represent (C.sub.1-C.sub.3)alkoxy; R.sup.1 represents H or halogen; U represents CH or N, or, in case “- - - - -” is absent, U represents CH.sub.2 or NH; V represents CH or N; R.sup.2 represents H or a group of the formula —CH.sub.2—R.sup.3, R.sup.3 being H, (C.sub.1-C.sub.3)alkyl or (C.sub.1-C.sub.3)hydroxyalkyl; A represents —(CH.sub.2).sub.p—, —CH.sub.2CH.sub.2CH(OH)— or —COCH.sub.2CH(OH)—; G represents a phenyl group which is substituted once or twice in the meta and/or para position(s) by substituents selected independently from (C.sub.1-C.sub.4)alkyl, (C.sub.1-C.sub.3)alkoxy and a halogen, or G is a group having one of the formulae G.sup.1 and G.sup.2 below ##STR00087## wherein Q is O or S and X is CH or N; and Y.sup.1, Y.sup.2 and Y.sup.3 each represent CH, or Y.sup.1 and Y.sup.3 each represent CH and Y.sup.2 represents N, or Y.sup.1 represents N, Y.sup.2 represents CH or N and Y.sup.3 represents CH, or Y.sup.1 and Y.sup.2 each represent CH and Y.sup.3 represents N; and n is 0 when A represents —CH.sub.2CH.sub.2CH(OH)— or —COCH.sub.2CH(OH)—, and n is 0, 1 or 2 when A represents (CH.sub.2).sub.p, p being 1, 2, 3 or 4, with the proviso that the sum of n and p is then 2, 3 or 4; or a salt of such a compound.

4. The compound of formula I according to claim 1, which is also a compound of formula I.sub.P1 ##STR00088## wherein “- - - - -” is a bond or is absent; R.sup.1 represents H or halogen; V represents CH or N; U represents CH or N, or, in case “- - - - -” is absent, U represents CH.sub.2 or NH; G represents a phenyl group which is substituted once or twice in the meta and/or para position(s) by substituents selected independently from (C.sub.1-C.sub.4)alkyl, (C.sub.1-C.sub.3)alkoxy and a halogen, or G is a group having one of the formulae G.sup.1 and G.sup.2 below ##STR00089## wherein Q is O or S and X is CH or N; and Y.sup.1, Y.sup.2 and Y.sup.3 each represent CH, or Y.sup.1 and Y.sup.3 each represent CH and Y.sup.2 represents N, or Y.sup.1 represents N, Y.sup.2 represents CH or N and Y.sup.3 represents CH, or Y.sup.1 and Y.sup.2 each represent CH and Y.sup.3 represents N; and n is 0, 1 or 2 and p is 1, 2 or 3, with the proviso that the sum of n and p is either 2 or 3; or a salt of such a compound.

5. The compound of formula I according to claim 1, which is also a compound of formula I.sub.CE ##STR00090## wherein “- - - - -” is a bond, V represents CH and U represents CH or N, or “- - - - -” is a bond, V represents CR.sup.6 and U represents CH, or also “- - - - -” is a bond, V represents N and U represents CH, or “- - - - -” is absent, V represents CH and U represents CH.sub.2, NH or NR.sup.9; R.sup.0 represents H or, in the case “- - - - -” is a bond, may also represent (C.sub.1-C.sub.3)alkoxy; R.sup.1 represents H or halogen; V represents CH, CR.sup.6 or N; R.sup.2 represents H, acetyl or a group of the formula —CH.sub.2—R.sup.3; R.sup.3 represents hydrogen, (C.sub.1-C.sub.3)alkyl or (C.sub.1-C.sub.3)hydroxyalkyl; R.sup.4 represents H or, in the cases wherein n is not 0 and R.sup.5 is H, may also represent OH; R.sup.5 represents H, (C.sub.1-C.sub.3)alkyl, (C.sub.1-C.sub.3)hydroxyalkyl, (C.sub.1-C.sub.3)aminoalkyl, (C.sub.1-C.sub.3)alkoxy(C.sub.1-C.sub.3)alkyl, carboxy or (C.sub.1-C.sub.3)alkoxycarbonyl; R.sup.6 represents (C.sub.1-C.sub.3)hydroxyalkyl, carboxy, (C.sub.1-C.sub.3)alkoxycarbonyl or a group —(CH.sub.2).sub.q—NR.sup.7R.sup.8 wherein q is 1, 2 or 3 and each of R.sup.7 and R.sup.8 independently represents H or (C.sub.1-C.sub.3)alkyl or R.sup.7 and R.sup.8 form together with the nitrogen atom bearing them a pyrrolidinyl or piperidinyl ring; R.sup.9 represents (C.sub.1-C.sub.3)alkyl, 2-hydroxy-ethyl, 2-hydroxy-propyl or 3-hydroxy-propyl; A represents —(CH.sub.2).sub.p—, —CH.sub.2CH.sub.2CH(OH)— or —COCH.sub.2CH(OH)—; G represents a phenyl group which is substituted once or twice in the meta and/or para position(s) by substituents selected independently from (C.sub.1-C.sub.4)alkyl, (C.sub.1-C.sub.3)alkoxy and a halogen, or G is a group having one of the formulae G.sup.1 and G.sup.2′ below ##STR00091## wherein Q is O or S and X is CH or N; and each of Y.sup.1 and Y.sup.3 represents CH, or one of Y.sup.1 and Y.sup.3 represents N and the other represents CH; and n is 0 when A represents —CH.sub.2CH.sub.2CH(OH)— or —COCH.sub.2CH(OH)—, and n is 0, 1 or 2 when A represents (CH.sub.2).sub.p, p being 1, 2, 3 or 4, with the proviso that the sum of n and p is then 2, 3 or 4; or a salt of such a compound.

6. The compound of formula I according to claim 1, wherein R.sup.1 represents fluorine; or a salt of such a compound.

7. The compound of formula I according to claim 1, wherein V represents CH; or a salt of such a compound.

8. The compound of formula I according to claim 1, wherein V represents N; or a salt of such a compound.

9. The compound of formula I according to claim 1, wherein “- - - - -” is a bond and U represents CH or N; or a salt of such a compound.

10. The compound of formula I according to claim 1, wherein “- - - - -” is absent and U represents CH.sub.2, NH or NR.sup.9; or a salt of such a compound.

11. The compound of formula I according to claim 1, wherein G is a group of the formula ##STR00092## wherein Q represents O or S; or a salt of such a compound.

12. The compound of formula I according to claim 1, wherein: “- - - - -” is a bond and V represents CH and U represents CH or N or V represents N and U represents CH; R.sup.0 represents H; R.sup.1 represents H or fluorine; R.sup.2 represents H; R.sup.4 represents H; R.sup.5 represents H, methyl, hydroxymethyl or aminomethyl; n is 0 and A represents —(CH.sub.2).sub.p— wherein p is 2, 3 or 4, or n is 1 and A represents —(CH.sub.2).sub.p— wherein p is 1, 2 or 3; and G is a group having the formula G.sup.1 below ##STR00093## wherein X is CH or N and Q is O or S; or a salt of such a compound.

13. The compound of formula I according to claim 1, wherein: “- - - - -” is absent and U represents NH or NR.sup.9 wherein R.sup.9 is methyl; R.sup.0 represents H; R.sup.1 represents H or fluorine; R.sup.2 represents H; each of R.sup.4 and R.sup.5 represents H; n is 0 and A represents —(CH.sub.2).sub.p— wherein p is 2, 3 or 4, or n is 1 and A represents —(CH.sub.2).sub.p— wherein p is 1, 2 or 3; and G is a group having the formula G.sup.1 below ##STR00094## wherein X is CH or N and Q is O or S; or a salt of such a compound.

14. The compound of formula I according to claim 1, wherein the compound is: 9-fluoro-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 9-fluoro-1-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 9-fluoro-1-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 9-fluoro-1-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 9-fluoro-1-({2-[3-(3-fluoro-4-methyl-phenyl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 1-(2-{[(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-ethyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 9-fluoro-1-(2-{[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 9-fluoro-1-(2-{[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 9-fluoro-1-(2-{[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 9-fluoro-1-(2-{[(R)-3-(3-fluoro-4-methyl-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 9-fluoro-1-{2-[2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; (4R)-4-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one; 3-fluoro-4-(2-{[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one; 3-fluoro-4-(2-{[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one; (4R)-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one; (4R)-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one; 9-fluoro-1-(2-{[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one; 9-fluoro-1-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one; 9-fluoro-1-(2-{[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one; 9-fluoro-1-(2-{[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one; 1-(2-{[(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-ethyl)-9-fluoro-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one; 9-fluoro-1-(2-{[(R)-3-(3-fluoro-4-methyl-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one; 3-fluoro-4-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one; 9-fluoro-1-({2-[(S)-2-oxo-3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one; 9-fluoro-1-({[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 1-({[(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 9-fluoro-1-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 9-fluoro-1-({[(R)-3-(3-fluoro-4-methyl-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 1-({[(R)-3-(4-ethoxy-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 9-fluoro-1-({[(R)-2-oxo-3-(4-propyl-phenyl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 1-({[(R)-3-(4-butyl-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; (S)-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one; (S)-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one; (S)-4-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one; 1-({2-[3-(2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 1-({2-[3-(2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-6-yl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 1-({2-[(R)-3-(4-ethoxy-phenyl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 9-fluoro-1-({2-[(R)-2-oxo-3-(4-propyl-phenyl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 1-({2-[(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 9-fluoro-1-({2-[2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; (S)-9-fluoro-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; (R)-9-fluoro-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 9-fluoro-1-({3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 9-fluoro-1-({3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 1-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; (S)-6-{2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one; (S)-6-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one; 6-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one; 9-fluoro-1-{2-[(R)-2-oxo-3-(4-propyl-phenyl)-oxazolidin-5-yl]-ethylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 1-({2-[(S)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 1-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; (S)-7-fluoro-6-((2-hydroxy-ethyl)-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-amino)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one; (S)-7-fluoro-6-((2-hydroxy-ethyl)-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propyl}-amino)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one; 9-fluoro-1-(2-{(3-hydroxy-propyl)-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 9-fluoro-1-(2-{(2-hydroxy-ethyl)-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; (S)-4-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one; (S)-4-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one; (R)-4-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one; 1-({[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 1-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 1-({3-[2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 3-fluoro-4-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one; (S)-1-{2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; (S)-1-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; (S)-1-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 9-fluoro-1-[((3-hydroxy-propyl)-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethyl}-amino)-methyl]-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 9-fluoro-1-[((2-hydroxy-ethyl)-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethyl}-amino)-methyl]-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 9-fluoro-1-((3-hydroxy-propyl)-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-amino)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 9-fluoro-1-((2-hydroxy-ethyl)-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-amino)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 3-fluoro-4-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one; 3-fluoro-4-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one; 3-fluoro-4-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-4, 5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one; 3-fluoro-4-({[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one; 3-fluoro-4-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one; 3-fluoro-4-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one; 6-({[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one; 1-{2-[(S)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-yl]-ethylamino}-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; N—((S)-9-fluoro-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-3-hydroxy-3-[2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propionamide; 6-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one; 9-fluoro-1-{3-hydroxy-3-[2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; (R)-4-oxo-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-7-carboxylic acid ethyl ester; (R)-7-hydroxymethyl-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; (R)-4-oxo-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-7-carboxylic acid; (R)-7-dimethylaminomethyl-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; (R)-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-7-pyrrolidin-1-ylmethyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; (R)-3-fluoro-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one; (R)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one; (R)-3-fluoro-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one; (R)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one; (R)-3-fluoro-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one; (R)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one; (R)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][ 1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one; (S)-3-fluoro-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one; (S)-3-fluoro-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one; (S)-3-fluoro-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one; (S)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one; (S)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one; (S)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one; (S)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4, 5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one; 9-fluoro-1-(methyl-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-amino)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 6-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one; (RS)-6-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one; 6-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one; (R)-1-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; (R)-1-{2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 9-fluoro-1-{4-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-butylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; (S)-7-fluoro-6-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2,5,6-tetrahydro-pyrrolo[1,2,3-de]quinoxalin-3-one; (1R*,2R*)-4-oxo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylic acid methyl ester; (1R*,2R*)-4-oxo-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylic acid methyl ester; (1R*,2R*)-2-hydroxymethyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; (1R*,2R*)-2-hydroxymethyl-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; (1R*,2R*)-2-methoxymethyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; (1R*,2S*)-2-methyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; (1R*,2S*)-2-methyl-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; (1R*,2S*)-2-methyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; (1R*,2S*)-2-methyl-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; (1R*,2R*)-2-(1-hydroxy-1-methyl-ethyl)-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-y]quinolin-4-one; N-(9-fluoro-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-N-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-acetamide; (S)-4-hydroxy-4-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethyl amino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one; 9-fluoro-1-hydroxy-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 1-({[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; (1R*,2R*)-9-fluoro-4-oxo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylic acid methyl ester; (1R*,2R*)-9-fluoro-2-hydroxymethyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; (1R*,2S*)-9-fluoro-2-methyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; (1R*,2S*)-9-fluoro-2-methyl-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; (1R*,2S*)-9-fluoro-2-methyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; (1R*,2R*)-9-fluoro-4-oxo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylic acid; 9-fluoro-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one; (1R*,2S*)-2-aminomethyl-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 9-fluoro-1-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 9-fluoro-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one; 7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1-methyl-1,2,5,6-tetrahydro-pyrrolo[1,2,3-de]quinoxalin-3-one; or 7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1-(3-hydroxypropyl)-1,2,5,6-tetrahydro-pyrrolo[1,2,3-de]quinoxalin-3-one; or a salt of such a compound.

15. A pharmaceutical composition comprising, as active principle, the compound of formula I as defined in claim 1, or a pharmaceutically acceptable salt thereof, and at least one therapeutically inert excipient.

16. The compound of claim 2, wherein R.sup.1 represents a halogen of F or Br.

17. A method for preventing or treating a bacterial infection in a patient, comprising administering to said patient a pharmaceutically active amount of compound of formula I as defined in claim 1, or a pharmaceutically acceptable salt thereof.

Description

EXAMPLES

(1) All temperatures are stated in ° C. Compounds are characterized by .sup.1H-NMR (300 MHz) (Varian Oxford); or by .sup.1H-NMR (400 MHz) (Bruker Advance 400). Chemical shifts 68 are given in ppm relative to the solvent used; multiplicities: s=singlet, d=doublet, t=triplet, q=quadruplet, p=pentuplet, hex=hexet, hep=heptet, m=multiplet, br.=broad, coupling constants are given in Hz. Alternatively compounds are characterized by LC-MS (Sciex API 2000 with Agilent 1100 Binary Pump with DAD and ELSD or an Agilent quadrupole MS 6140 with Agilent 1200 Binary Pump, DAD and ELSD); by TLC (TLC plates from Merck, Silica gel 60 F.sub.254); or by melting point. Compounds are purified by chromatography on Silica gel 60A. NH.sub.4OH as used for CC is 25% aq.

(2) The HPLCs are done over a stationary phase such as a rapid resolution Zorbax SB C18 (1.8 μm) column, or a rapid resolution Zorbax Eclipse Plus C18 (1.8 μm) column. Typical HPLC conditions are a gradient of eluent A (water:MeCN 95:5 with 0.1% of formic acid, in presence or not of 5 mmol/L ammonium formate) and eluent B (MeCN:water 95:5 with 0.1% of formic acid, in the presence or not of 5 mmol/L ammonium formate), at a flow rate of 0.8 to 5 mL/min. Racemates can be separated into their enantiomers as described before. Preferred conditions of chiral HPLC are: ChiralPak AD (4.6×250 mm, 5 μm) column, using an isocratic mixture (e.g. at a ratio of 10/90) of eluent A (EtOH, in presence of diethylamine in an amount of eg. 0.1%) and eluent B (Hex), at rt, at a flow rate of e.g. 0.8 mL/min.

(3) General Procedures:

(4) Procedure A: LAH Reduction of Esters:

(5) To a solution of ester (1 mmol) in THF (15 mL), cooled to −10° C., is added in one portion LAH (3.5 eq.). The mixture is stirred at the same temperature for 0.5 h, then at 0° C./rt until completion of the reaction (1-3 h). Water (0.4 mL) is carefully added, followed by 2M NaOH (0.8 mL) and water (0.4 mL). After stirring for 5 min, Na.sub.2SO.sub.4 (1 g) is added and the mixture is stirred for 15 min. The solids are filtered off and thoroughly washed with EA. The filtrate is concentrated under reduced pressure.

(6) Procedure B: Boc Deprotection:

(7) The Boc protected amine (1 mmol) is dissolved in DCM (5 mL) and treated with Et.sub.3SiH (optional; 0.2 mL, 1.1 eq.) and TFA (2 mL). The mixture is stirred at rt for 1 h, concentrated in vacuo and taken up in DCM/aq. NH.sub.4OH. The org. layer is washed with water, dried over MgSO.sub.4 and concentrated under reduced pressure.

(8) Procedure C: Alkylation of Amines with Mesylates:

(9) A solution of amine (1.0-2.3 mmol), mesylate (1 mmol) and DIPEA (1.1 mmol) in dry DMSO is heated to 70° C. until completion of the reaction (1-5 days). After cooling, water and EA are added and the phases are separated. The aq. layer is extracted two more times with EA and the combined org. layers are washed with water (3×) and brine, dried over MgSO.sub.4 and concentrated under reduced pressure. The residue is then purified by CC.

(10) Procedure D: Alkylation of Amines with Iodides:

(11) A solution of amine (1 mmol), iodide (1 mmol) and DIPEA (1.1 mmol) in dry DMSO is heated to 70° C. until completion of the reaction (1-3 days). After cooling, water and EA are added and the phases are separated. The aq. layer is extracted two more times with EA and the combined org. layers are washed with water (3×) and brine, dried over MgSO.sub.4 and concentrated under reduced pressure. The residue is then purified by CC.

(12) Procedure E: Reductive Amination:

(13) A solution of amine (1 mmol) and aldehyde (1 mmol) in DCE/MeOH (1-1 to 4-1, 10 mL) is treated with NaBH(OAc).sub.3 (2 mmol). The mixture is stirred at rt until completion of the reaction (1-4 h), diluted with DCM and treated with aq. NH.sub.4OH. The phases are separated. The aq. layer is extracted two more times with DCM and the combined org. layers are washed with water and brine, dried over MgSO.sub.4 and concentrated under reduced pressure. The residue is then purified by CC.

(14) Procedure F: Hydrogenation:

(15) A solution of unsaturated substrate (1 mmol) in MeOH (20 mL) and AcOH (optional, 20 mL) is hydrogenated over 10% Pd/C (200 mg) for 20 h. The catalyst is filtered off, washed with MeOH/DCM and concentrated. Water and 28% aq. NH.sub.4OH are added and the mixture is extracted with DCM/MeOH 9:1. The org. layer is dried over MgSO.sub.4, concentrated and purified by CC.

(16) Procedure G: Boc Protection:

(17) Boc.sub.2O (1.05 eq.) and TEA (1.5 eq.) are added at rt to a solution of the corresponding amine (1.0 eq.) in THF. The reaction mixture is stirred at rt for 1 h, concentrated to dryness and purified by CC.

(18) Procedure H: Mesylate Formation:

(19) TEA or DIPEA (2 eq.) and MsCl (1.2 eq.) are added at 0° C. to a solution of the required alcohol (1 eq.) in DCM or DCE. The reaction is stirred 1 h at this temperature. In the case the resulting mesylate can undergo cyclization to form a tricyclic system, the reaction mixture is further stirred between rt and 45° C. for 6 to 72 h. Sat. aq. NaHCO.sub.3 is then added and the mixture is extracted with DCM (3×). The combined org. layers are dried over MgSO.sub.4, filtered and concentrated under reduced pressure to afford the desired mesylate which can be used as such in a further step.

(20) Procedure I: Oxazolidinone Formation with CDI:

(21) A solution of the required aminoalcohol (1 eq.) in THF is treated with CDI (1.5 eq.) and heated at 50° C. overnight. The mixture is cooled to rt, diluted with EA and washed with water. The org. layer is washed with 0.5M HCl (optionally) and water, dried over MgSO.sub.4 and concentrated. The residue is either triturated with an org. solvent, crystallized from Hept/EA or purified by CC.

(22) Procedure J: Deprotection of TBDMS Ethers:

(23) A solution of TBDMS ether (1 eq) in THF is treated with TBAF (1M solution in THF, 1.2 eq.) at 0° C. The solution is stirred at 0° C. for 6 h. The mixture is partitioned between water and EA and the aq. phase is extracted with EA (3×). The combined org. layers are washed with water (3×) and brine, dried over MgSO.sub.4 and concentrated under reduced pressure. The residue is triturated with an org. solvent or purified by CC.

(24) Procedure K: Finkelstein-Like Iodide Formation:

(25) A suspension of the mesylate (1 eq.) and NaI (3 eq.) in 2-butanone is heated at 85° C. between 3 h and 3 days. After cooling, the mixture is diluted with ether/EA and treated with 10% aq. Na.sub.2S.sub.2O.sub.3. After stirring for 10 min, the phases are separated and the aq. layer was washed with EA. The combined org. layers are washed with water (2×), dried over MgSO.sub.4 and concentrated under reduced pressure. The residue is triturated with an org. solvent.

(26) Procedure L: Asymmetric Dihydroxylation (Chem. Rev. (1994), 94, 2483):

(27) A mixture of olefin (1 mmol) in t-BuOH/H.sub.2O (1:1, 10 mL) at rt is treated with methylsulfonamide (1 eq.) and AD-mix α or β (1.5 g). The mixture is vigorously stirred at rt until completion of reaction, Na.sub.2S.sub.2O.sub.3 (1.5 g) is added and the mixture diluted with EA (30 mL). The phases are separated and the aq. phase is extracted once more with EA. The combined org. layers are washed with water and brine, dried over MgSO.sub.4 and concentrated. The residue is purified by CC.

(28) Procedure M: TBDMS Protection:

(29) A solution of alcohol (1 eq.) and imidazole (1.1 eq.) in THF (10 mL/mmol) at 0° C. is treated dropwise with a solution of TBDMSCl (1 eq.) in THF. The mixture is stirred at rt until complete conversion. The mixture is diluted with EA, washed with water and brine, dried over MgSO.sub.4 and concentrated. The residue is purified by CC.

(30) Procedure N: Mitsunobu Reaction:

(31) To a solution of alcohol (1 eq.) and PPh.sub.3 (1.1 eq.) in THF (2 ml/mmol) cooled to 0° C., DPPA (1.1 eq.) and DIAD (1.2 eq.) are added dropwise and the mixture warmed to rt over 1 h and stirred at this temperature until completion of reaction. The mixture is concentrated under reduced pressure and the residue purified by CC.

(32) Procedure N: Mitsunob Reaction with Staudinger Conditions and Boc Protection:

(33) After performing procedure N with the alcohol (1 eq.) as previously described, the azide is dissolved in THF/water (9:1) and treated with PPh.sub.3 (1.2 eq.) and the resulting solution heated at 50° C. until complete conversion to the amine. The mixture is cooled an treated with Boc.sub.2O (1.5 eq) and stirred at rt overnight. The volatiles are removed under reduced pressure and the residue purified by CC to give the Boc-protected amine.

Preparation A: rac-1-aminomethyl-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

A.i. (7-fluoro-2-methoxy-quinolin-8-yl)-acetonitrile

(34) To a solution of 8-bromomethyl-7-fluoro-2-methoxy-quinoline (20.0 g, 74 mmol; prepared as in WO 2007/081597) in DMF (530 mL) was added KCN (22.1 g, 339 mmol) and the mixture was stirred at 70° C. overnight. The mixture was concentrated, water and EA were added and the aq. layer was extracted with EA. The combined org layers were washed with brine, dried over MgSO.sub.4 and concentrated to afford the title intermediate as a beige solid (16.13 g, 100% yield).

(35) MS (ESI, m/z): 217.4 [M+H.sup.+].

A.ii. (7-fluoro-2-methoxy-quinolin-8-yl)-acetic acid methyl ester

(36) To a solution of intermediate A.i (16.1 g, 75 mmol) in MeOH (270 mL) was added TMSCl (32 mL, 3.38 eq) and the solution was stirred at 80° C. for 3 h. The mixture was concentrated under reduced pressure and partitioned between EA and water. The phases were separated and the aq. layer was extracted with EA. The combined org. layers were washed with 2M NaOH, water and brine, dried over MgSO.sub.4, concentrated and purified by CC (DCM) to afford the title intermediate as a colourless solid (8.13 g, 44% yield).

(37) MS (ESI, m/z): 250.2 [M+H.sup.+].

A.iii. rac-3-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-2-(7-fluoro-2-methoxy-quinolin-8-yl)-propionic acid methyl ester

(38) To a solution of LiHMDS (31.3 mL, 1M in THF) in THF (40 mL) was added at −78° C. a solution of intermediate A.ii (6.50 g, 26 mmol) in THF (50 mL) over 10 min. After stirring for 1 h at −78° C., a solution of N-(bromomethyl)phthalimide in THF (50 mL) was added dropwise over 10 min. The mixture was stirred at −78° C. for 1 h and then at rt overnight. The resulting solution was quenched with 1N HCl (260 mL) and extracted with DCM. The combined org. layers were washed with water, dried over MgSO.sub.4, concentrated and purified by CC (Hept/EA 1:1). The resulting solid was triturated with EA to afford the title intermediate as a colourless solid (2.42 g, 23% yield).

(39) MS (ESI, m/z): 409.3 [M+H.sup.+].

A.iv. rac-3-amino-2-(7-fluoro-2-methoxy-quinolin-8-yl)-propionic acid methyl ester

(40) To a suspension of intermediate A.iii (2.40 g, 5.88 mmol) in EtOH (40 mL) was added dropwise hydrazine monohydrate (1.43 mL, 5 eq.) at rt. The mixture was stirred for 2 h at rt and then concentrated. The residue was taken up in EA and 10% citric acid and the layers were separated. The aq. phase was treated another time with EA. The aq. phase was basified with NH.sub.4OH and extracted twice with DCM. The combined DCM phases were dried over MgSO.sub.4 and concentrated to afford the title intermediate as a pale yellow oil (1.62 g, 99% yield).

(41) MS (ESI, m/z): 279.4 [M+H.sup.+].

A.v. rac-3-tert-butoxycarbonylamino-2-(7-fluoro-2-methoxy-quinolin-8-yl)-propionic acid methyl ester

(42) Starting from intermediate A.iv (1.62 g, 5.82 mmol) and using procedure G, the title intermediate was obtained as a colourless solid (1.87 g, 85% yield).

(43) MS (ESI, m/z): 379.2 [M+H.sup.+].

A.vi. rac-[2-(7-fluoro-2-methoxy-quinolin-8-yl)-3-hydroxy-propyl]-carbamic acid tert-butyl ester

(44) Starting from intermediate A.v and using procedure A, the title intermediate was obtained as a colourless solid (1.69 g, 98% yield).

(45) MS (ESI, m/z): 351.3 [M+H.sup.+].

A.vii. rac-(9-fluoro-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-ylmethyl)-carbamic acid tert-butyl ester

(46) Starting from intermediate A.vi (1.68 g, 4.8 mmol) and using procedure H, the title intermediate was obtained as a beige solid (1.56 g, 100% yield).

(47) MS (ESI, m/z): 319.3 [M+H.sup.+].

A.viii. rac-1-aminomethyl-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(48) Starting from intermediate A.vii and using procedure B, the title compound was obtained as a pale orange solid (1.08 g, quant.).

(49) .sup.1H NMR (CDCl.sub.3) δ: 7.66 (d, J=9.4 Hz, 1H), 7.40 (dd, J=8.8, 4.7 Hz, 1H), 6.88 (m, 1H), 6.61 (d, J=9.4 Hz, 1H), 4.53 (dd, J=12.9, 9.4 Hz, 1H), 4.36 (dd, J=12.9, 4.7 Hz, 1H), 3.95 (m, 1H), 1.97 (m, 2H), 3.15 (m, 2H).

(50) MS (ESI, m/z): 219.2 [M+H.sup.+].

Preparation B: rac-1-(2-amino-ethyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

B.i. rac-3-cyano-2-(7-fluoro-2-methoxy-quinolin-8-yl)-propionic acid methyl ester

(51) LiHMDS (18.4 mL, 1.1 eq., 1M in THF) was added at −78° C. within 15 min to a solution of intermediate A.ii (4.17 g, 16.7 mmol) in THF (40 mL). The resulting mixture was stirred at −78° C. for 2 h. Bromoacetonitrile (3.0 g, 1.5 eq.) was added within 20 min and stirring was continued at −78° C. for 2 h. The reaction was quenched with water and extracted with EA (3×). The combined org. phases were washed with brine, dried over MgSO.sub.4, filtered and concentrated. The residue was purified by CC (Hept/EA 2:1 to 1:1) to afford the title intermediate as a yellow solid (3.96 g, 82% yield).

(52) MS (ESI, m/z): 289.4 [M+H.sup.+].

B.ii. rac-4-amino-2-(7-fluoro-2-methoxy-quinolin-8-yl)-butan-1-ol

(53) To a solution of AlCl.sub.3 (4.0 g, 30 mmol) in ether (150 mL) were added LAH (30 mL, 1M in THF) dropwise within 10 min at −78° C. After stirring for 15 min, a suspension of intermediate B.i (3.94 g, 13.7 mmol) in ether (120 mL) was added within 15 min. The suspension was then stirred at rt for 4 h, cooled to 0° C., quenched with sat. aq. Na.sub.2SO.sub.4. The mixture was basified with NH.sub.4OH and extracted with EA (3×). The combined org. phases were dried over Na.sub.2SO.sub.4, filtered and concentrated to afford the title intermediate as a yellow oil (3.86 g, quant.) which was used as such in the next step.

(54) MS (ESI, m/z): 265.4 [M+H.sup.+].

B.iii. rac-[3-(7-fluoro-2-methoxy-quinolin-8-yl)-4-hydroxy-butyl]-carbamic acid tert-butyl ester

(55) Starting from intermediate B.ii (3.85 g, 14.57 mmol) and using procedure G, the title intermediate was obtained as a yellow oil (2.69 g, 51% yield).

(56) MS (ESI, m/z): 365.1 [M+H.sup.+].

B.iv. rac-[2-(9-fluoro-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-ethyl]-carbamic acid tert-butyl ester

(57) Starting from intermediate B.iii (2.68 g, 7.4 mmol) and using procedure H, the title intermediate was obtained as a pale orange solid (2.67 g, quant.) which was used as such in the next step.

(58) MS (ESI, m/z): 333.1 [M+H.sup.+].

B.v. rac-1-(2-amino-ethyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(59) Starting from intermediate B.iv and using procedure B, the title compound was obtained after CC (DCM/MeOH/NH.sub.4OH 1000:50:4) as a pale orange solid (1.34 g, 72% yield).

(60) .sup.1H NMR (CDCl.sub.3) δ: 7.68 (d, J=9.3 Hz, 1H), 7.40 (dd, J=8.8, 4.8 Hz, 1H), 6.89 (m, 1H), 6.63 (d, J=9.5 Hz, 1H), 4.56 (dd, J=12.8, 9.3 Hz, 1H), 4.21 (dd, J=12.5, 4.8 Hz, 1H), 4.00 (m, 1H), 2.89 (m, 2H), 2.18 (m, 1H), 1.86 (m, 1H), 1.24 (m, 2H).

(61) MS (ESI, m/z): 233.5 [M+H.sup.+].

Preparation C: rac-1-amino-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

C.i. rac-bromo-(7-fluoro-2-methoxy-quinolin-8-yl)-acetic acid methyl ester

(62) NBS (1.6 g) and AIBN (0.1 g) were added to a mixture of intermediate A.ii (1.50 g, 6.0 mmol) in trifluorotoluene (30 mL). The mixture was heated at 80° C. under a sunlamp beam for 5 h. After cooling, the reaction mixture was concentrated. The residue was taken in EA and washed twice with 10% sodium thiosulfate, dried over Na.sub.2SO.sub.4, filtered and concentrated to dryness. The residue was triturated with Hept/EA to afford the title intermediate as a colourless solid (1.42 g, 72% yield).

(63) MS (ESI, m/z): 328.2 [M+H.sup.+].

C.ii. rac-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-(7-fluoro-2-methoxy-quinolin-8-yl)-acetic acid methyl ester

(64) To a solution of intermediate C.i (1.31 g, 4.0 mmol) in dry DMF (25 mL) was added potassium phthalimide (1.24 g, 6.6 mmol) under Ar. The resulting solution was stirred at 120° C. for 1 h. After cooling to rt, water was added and the mixture was extracted with EA. The org. layer was washed with water and brine, dried over MgSO.sub.4 and concentrated. The residue was crystallized from Hept/EA to afford the title intermediate as a beige solid (1.04 g, 66% yield).

(65) MS (ESI, m/z): 395.1 [M+H.sup.+].

C.iii. rac-amino-(7-fluoro-2-methoxy-quinolin-8-yl)-acetic acid methyl ester

(66) To a solution of intermediate C.ii (714 mg, 1.81 mmol) in EtOH (10 mL) was added dropwise hydrazine monohydrate (0.9 mL, 10 eq.) at rt. The mixture was stirred for 3 h at rt, after which a precipitate had formed, which was filtered off. The filtrate was concentrated under reduced pressure and partitioned between EA and 10% citric acid. The aq. layer was washed once more with EA and then basified using NH.sub.4OH. The aq. layer was extracted with DCM and the org. layer was concentrated under reduced pressure to afford the title intermediate as a colourless solid (398 mg, 83% yield).

(67) MS (ESI, m/z): 265.5 [M+H.sup.+].

C.iv. rac-tert-butoxycarbonylamino-(7-fluoro-2-methoxy-quinolin-8-yl)-acetic acid methyl ester

(68) Starting from intermediate C.iii (380 mg, 1.44 mmol) and using procedure G, the title intermediate was obtained as a colourless solid (560 mg, 100% yield).

(69) MS (ESI, m/z): 365.0 [M+H.sup.+].

C.v. rac-[1-(7-fluoro-2-methoxy-quinolin-8-yl)-2-hydroxy-ethyl]-carbamic acid tert-butyl ester

(70) Starting from intermediate C.iv and using procedure A, the title intermediate was obtained as a pale yellow solid (473 mg, 92% yield).

(71) MS (ESI, m/z): 337.3 [M+H.sup.+].

C.vi. rac-(9-fluoro-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-carbamic acid tert-butyl ester

(72) TEA (0.4 mL, 2 eq.) and MsCl (0.13 mL, 1.2 eq.) were added at 0° C. to a solution of intermediate C.v (470 mg, 1.40 mmol) in DCM (10 mL). The reaction proceeded for 20 min at this temperature. Sodium bicarbonate and DCM were added. The two layers were decanted and the aq. layer was extracted once more with DCM. The combined org. layers were dried over Na.sub.2SO.sub.4, filtered and concentrated to dryness. The residue was carried on without further purification. A solution of the crude mesylate in toluene (20 mL) was heated at 85° C. overnight. After cooling to rt, water and EA were added and the layers separated. The aq. layer was extracted once more with EA and the combined org. layers were washed with saturated NaHCO.sub.3 and concentrated. The residue was triturated with ether/EA to afford the title intermediate as a colourless solid (193 mg, 45% yield).

(73) MS (ESI, m/z): 305.0 [M+H.sup.+].

C.vii. rac-1-amino-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(74) Starting from intermediate C.vi and using procedure B, the title compound was obtained as a beige solid (128 mg, 100% yield).

(75) .sup.1H NMR (DMSO-d.sub.6) δ: 7.88 (d, J=9.4 Hz, 1H), 7.61 (dd, J=8.5, 5.0 Hz, 1H), 6.99 (dd, J=9.7, 8.8 Hz, 1H), 6.49 (d, J=9.4 Hz, 1H), 4.92 (dd, J=8.8, 4.4 Hz, 1H), 4.44 (dd, J=12.9, 8.8 Hz, 1H), 3.86 (dd, J=12.6, 3.8 Hz, 1H), 2.29 (s, 2H).

(76) MS (ESI, m/z): 205.1 [M+H.sup.+].

Preparation D: (R)-4-amino-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

D.i. (R)-2-azido-2-(6-methoxy-[1,5]naphthyridin-4-yl)-ethanol and (S)-2-azido-1-(6-methoxy-[1,5]naphthyridin-4-yl)-ethanol

(77) A mixture of (S)-2-methoxy-8-oxiranyl-[1,5]naphthyridine (4 g, 20 mmol; prepared as in WO 2006/002047), NH.sub.4Cl (2.7 g, 2.5 eq) and NaN.sub.3 (3.2 g, 2.5 eq.) in MeOH (100 mL) and water (2 mL) was heated at 65° C. for 4 h, filtered and concentrated in vacuo. The residue was taken up in EA and washed with sat. NaHCO.sub.3 and brine, dried over MgSO.sub.4 and concentrated. The residue was purified by CC (Hept/EA 1:1, 1:2, EA) to give a 3:2 mixture of regioisomers (5 g, 100% yield) which was used as such in the next step.

D.ii. [(R)-2-hydroxy-1-(6-methoxy-[1,5]naphthyridin-4-yl)-ethyl]-carbamic acid tert-butyl ester

(78) A solution of intermediate D.i (mixture of isomers, 5 g, 20.7 mmol) in THF/MeOH 1:1 (200 mL) was hydrogenated over Pd/C (10%, 2.2 g) and 1 bar of H.sub.2 for 1 h. The catalyst was filtered off and the filtrate concentrated under reduced pressure. The residue was dissolved in DCM (150 mL) and Boc.sub.2O (6.8 g, 1.5 eq.) was added. The mixture was stirred at rt for 2 h, concentrated in vacuo and purified by CC (EA/Hept 2:1, EA, EA/MeOH 9:1) to give the more polar, desired isomer as a colourless foam (2.8 g, 43% yield).

(79) .sup.1H NMR (DMSO-d.sub.6) δ: 8.72 (d, J=4.4 Hz, 1H), 8.24 (d, J=9.1 Hz, 1H), 7.56 (d, J=4.4 Hz, 1H), 7.33 (d, J=8.5 Hz, 1H), 7.25 (d, J=9.1 Hz, 1H), 5.64 (m, 1H), 3.99 (m, 3H), 3.78 (m, 1H), 3.58 (dd, J=10.8, 7.0 Hz, 1H), 1.35 (s, 9H).

D.iii. ((R)-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de][1,5]naphthyridin-4-yl)-carbamic acid tert-butyl ester

(80) Starting from intermediate D.ii (2.8 g, 8.8 mmol) and using procedure H, the title intermediate was obtained as an off-white solid (1.2 g, 47% yield) after CC (EA, EA/MeOH 9:1) and crystallisation from ether/EA.

(81) MS (ESI, m/z): 288.4 [M+H.sup.+].

D.iv. (R)-4-amino-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(82) A solution of intermediate D.iii (1 g, 3.48 mmol) in dioxane was treated with 4N HCl in dioxane (4 mL). The beige suspension was stirred at rt overnight, filtered and washed with ether and dried to give the dihydrochloride (475 mg, 52% yield). The free base was generated with the use of ion exchange resin (Dowex 50), eluting with methanolic ammonia to give a beige solid (0.3 g).

(83) .sup.1H NMR (DMSO-d.sub.6) δ: 8.55 (d, J=4.7 Hz, 1H), 7.99 (d, J=9.7 Hz, 1H), 7.65 (dd, J=4.7, 0.9 Hz, 1H), 6.82 (d, J=9.7 Hz, 2H), 5.12 (ddd, J=8.8, 4.1, 0.9 Hz, 1H), 4.53 (dd, J=13.2, 8.8 Hz, 1H), 4.05 (m, 3H).

Preparation E: rac-4-aminomethyl-3-fluoro-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

E.i. 2-(3-fluoro-6-methoxy-[1,5]naphthyridin-4-yl)-malonic acid diethyl ester

(84) Diethyl malonate (12.4 mL, 81.7 mmol) was added to a suspension of NaH (3.0 g, 47.9 mmol, 60% in mineral oil) in dioxane (35 mL). The mixture was stirred at rt for 5 min and then heated at 80° C. for 1 h. After cooling to rt, CuBr (1.4 g, 9.6 mmol) and 8-bromo-7-fluoro-2-methoxy-[1,5]naphthyridine (7.0 g, 27.2 mmol, prepared according to WO 2007/122258) were added. The mixture was stirred at 100° C. for 6 h. After cooling to rt, 10% NaHSO.sub.4 (100 mL) was added. The mixture was stirred for 30 min at rt. The two layers were decanted and the aq. layer was extracted three times with EA (3×150 mL). The combined org. layers were washed with brine, dried over Na.sub.2SO.sub.4, filtered and concentrated to dryness. The residue was purified by CC (Hept-EA 3:1 then 1:1) to afford the title intermediate as a yellow oil (8.22 g, 90% yield).

(85) MS (ESI, m/z): 337.3 [M+H.sup.+].

E.ii. (3-fluoro-6-methoxy-[1,5]naphthyridin-4-yl)-acetic acid ethyl ester

(86) Water (0.53 mL, 1.2 eq.) and LiCl (2.07 g, 2 eq.) were added to a solution of intermediate E.i (8.22 g, 24.4 mmol) in DMSO (170 mL). The mixture was heated to 110° C. for 16 h and another 2.34 g of LiCl were added. The mixture was further heated at 110° C. for 16 h. The solvent was then evaporated under reduced pressure (bath temperature=70° C., p=0.5 mbar). The residue was partitioned between 10% NaHSO.sub.4 (200 mL) and ether (200 mL). The aq. layer was extracted with ether (2×200 mL). The combined org. layers were filtered through a pad of silica gel. The filtrate was concentrated to dryness to afford the title intermediate as a brown oil (5.62 g, 87% yield).

(87) MS (ESI, m/z): 265.3 [M+H.sup.+].

E.iii. rac-3-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-2-(3-fluoro-6-methoxy-[1,5]naphthyridin-4-yl)-propionic acid ethyl ester

(88) To a solution of LiHMDS (4.54 mL, 1M in THF) in THF (11 mL) was added at −78° C. a solution of intermediate E.ii (1.0 g, 3.78 mmol) in THF (3 mL) over 10 min. After stirring for 1 h at −78° C. a solution of N-(bromomethyl)phthalimide (1.09 g, 1.2 eq.) in THF (4 mL) was added dropwise over 10 min. The mixture was stirred at −78° C. for 1 h and then at rt overnight. The resulting solution was quenched with 1N HCl and extracted with DCM. The combined org. layers were washed with water, dried over MgSO.sub.4, concentrated and purified by CC (Hept/EA 1:1) to afford the title intermediate as an off-white solid (0.361 g, 43% yield).

(89) MS (ESI, m/z): 424.4 [M+H.sup.+].

E.iv. rac-3-amino-2-(3-fluoro-6-methoxy-[1,5]naphthyridin-4-yl)-propionic acid ethyl ester

(90) To a suspension of intermediate E.iii (368 mg, 0.87 mmol) in EtOH (6 mL) was added dropwise hydrazine monohydrate (0.21 mL, 5 eq.) at rt. The mixture was stirred for 2 h at rt and then concentrated. The residue was taken up in EA and 10% citric acid and the layers were separated. The aq. phase was treated another time with EA. The aq. phase was basified with NH.sub.4OH and extracted twice with DCM. The combined DCM phases were dried over MgSO.sub.4 and concentrated to afford the title intermediate as a yellow oil (0.21 g, 82% yield).

(91) MS (ESI, m/z): 203.0 [M+H.sup.+].

E.v. rac-3-tert-butoxycarbonylamino-2-(3-fluoro-6-methoxy-[1,5]naphthyridin-4-yl)-propionic acid ethyl ester

(92) Starting from intermediate E.iv (0.21 g, 0.72 mmol) and using procedure G, the title intermediate was obtained as a pale yellow foam (0.23 g, 83% yield).

(93) MS (ESI, m/z): 394.2 [M+H.sup.+].

E.vi. rac-[2-(3-fluoro-6-methoxy-[1,5]naphthyridin-4-yl)-3-hydroxy-propyl]-carbamic acid tert-butyl ester

(94) Starting from intermediate E.v (0.225 g, 0.57 mmol) and using procedure A, the title intermediate was obtained as a yellow foam (0.20 g, 100% yield).

(95) MS (ESI, m/z): 202.2 [M+H.sup.+].

E.vii. rac-(3-fluoro-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de][1,5]naphthyridin-4-ylmethyl)-carbamic acid tert-butyl ester

(96) Starting from intermediate E.vi (0.20 g, 0.57 mmol) and using procedure H, the title intermediate was obtained as a beige solid (0.204 g, quant.) which was used as such in the next step.

(97) MS (ESI, m/z): 320.2 [M+H.sup.+].

E.viii. rac-4-aminomethyl-3-fluoro-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(98) Starting from intermediate E.vii and using procedure B, the title compound was obtained as a brown oil (17 mg, 13% yield).

(99) MS (ESI, m/z): 220.3 [M+H.sup.+].

Preparation F: rac-4-(2-amino-ethyl)-3-fluoro-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

F.i. rac-3-cyano-2-(3-fluoro-6-methoxy-[1,5]naphthyridin-4-yl)-propionic acid ethyl ester

(100) LiHMDS (4.2 mL, 1.1 eq., 1M in THF) was added at −78° C. within 15 min to a solution of intermediate E.ii (1.5 g, 5.68 mmol) in THF (15 mL). The resulting mixture was stirred at −78° C. for 2 h. Then bromoacetonitrile (1.02 g, 1.5 eq.) was added within 20 min and stirring was continued at −78° C. for 2 h. The reaction was quenched with water and extracted with EA (3×). The combined org. phases were washed with brine, dried over MgSO.sub.4, filtered and concentrated. The residue was purified by CC (Hept/EA 1:1) to afford the title intermediate as a yellow oil (1.30 g, 76% yield).

(101) MS (ESI, m/z): 304.2 [M+H.sup.+].

F.ii. rac-4-amino-2-(3-fluoro-6-methoxy-[1,5]naphthyridin-4-yl)-butan-1-ol

(102) To a solution of AlCl.sub.3 (1.3 g, 9.9 mmol) in ether (60 mL) were added LAH (9.9 mL, 1M in THF) dropwise within 10 min at −78° C. After stirring for 15 min a suspension of intermediate F.i (1.36 g, 4.50 mmol) in ether (50 mL) was added within 15 min. The suspension was then stirred for 1 h at −78° C. and for 1 h at −30° C. The mixture was then stirred for 2 h at 0° C., quenched with sat. aq. Na.sub.2SO.sub.4. The mixture was basified with NH.sub.4OH and extracted with EA (3×). The combined org. phases were dried over Na.sub.2SO.sub.4, filtered and concentrated. The residue was purified by CC (DCM/MeOH/NH.sub.4OH 1000:100:8) to afford the title intermediate as a yellow oil (0.30 g, 25% yield).

(103) MS (ESI, m/z): 266.3 [M+H.sup.+].

F.iii. rac-[3-(3-fluoro-6-methoxy-[1,5]naphthyridin-4-yl)-4-hydroxy-butyl]-carbamic acid tert-butyl ester

(104) Starting from intermediate F.ii (424 mg, 1.60 mmol) and using procedure G, the title intermediate was obtained as a yellow solid (360 mg, 62% yield).

(105) MS (ESI, m/z): 366.2 [M+H.sup.+].

F.iv. rac-[2-(3-fluoro-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de][1,5]naphthyridin-4-yl)-ethyl]-carbamic acid tert-butyl ester

(106) Starting from intermediate F.iii (360 mg, 0.99 mmol) and using procedure H, the title intermediate was obtained as a brown solid (360 mg, quant.) which was used as such in the next step.

(107) MS (ESI, m/z): 334.1 [M+H.sup.+].

F.v. rac-4-(2-amino-ethyl)-3-fluoro-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(108) Starting from intermediate F.iv and using procedure B, the title compound was obtained after CC (DCM/MeOH/NH.sub.4OH 1000:100:8) as a yellow solid (130 mg, 49% yield).

(109) MS (ESI, m/z): 234.3 [M+H.sup.+].

Preparation G: rac-6-amino-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

G.i. rac-2-azido-2-(3-methoxy-quinoxalin-5-yl)-ethanol

(110) A mixture of 2-methoxy-8-oxiranyl-quinoxaline (4.7 g, 23 mmol; prepared as in WO 2004/002490), NH.sub.4Cl (2.2 g, 1.8 eq.) and NaN.sub.3 (3.8 g, 2.5 eq.) in MeOH (60 mL) was heated at 65° C. for 5 h, filtered and concentrated in vacuo. The residue was taken up in EA and washed with sat. NaHCO.sub.3 and brine, dried over MgSO.sub.4 and concentrated. The residue was purified by CC (Hept/EA 1:1) to give the desired intermediate as a beige solid (4.4 g, 77% yield).

(111) .sup.1H NMR (CDCl.sub.3) δ: 8.52 (s, 1H), 8.02 (dd, J=8.5, 1.5 Hz, 1H), 7.77 (dd, J=7.3, 1.5 Hz, 1H), 7.60 (m, 1H), 5.90 (dd, J=7.6, 4.1 Hz, 1H), 4.13 (s, 3H), 4.01 (dd, J=11.4, 3.8 Hz, 1H), 3.87 (dd, J=11.4, 7.9 Hz, 1H).

G.ii. rac-[2-hydroxy-1-(3-methoxy-quinoxalin-5-yl)-ethyl]-carbamic acid tert-butyl ester

(112) A solution of intermediate G.i (4.48 g, 18.2 mmol) in THF (100 mL) and water (3.2 mL) was treated with PPh.sub.3 (5.3 g, 1.1 eq) and heated at 50° C. for 2 h. The mixture was concentrated to dryness and redissolved in ether/EA. The org. phase was extracted twice with 1M HCl. The organic phase was discarded and the aqueous phase basified with 6N NaOH and extracted with DCM, dried over MgSO.sub.4 and concentrated. The residue was dissolved in DCM (150 mL) and treated with Boc.sub.2O (4.8 g, 1.2 eq.). The mixture was stirred at rt for 1 h, concentrated in vacuo and purified by CC (EA/Hept 2:1, EA) to give the desired intermediate as a colourless foam (4.9 g, 84% yield).

(113) .sup.1H NMR (DMSO-d.sub.6) δ: 8.60 (s, 1H), 7.87 (dd, J=8.2, 1.5 Hz, 1H), 7.70 (m, 1H), 7.58 (m, 1H), 7.26 (m, 1H), 5.64 (td, J=7.6, 4.1 Hz, 1H), 4.76 (t, J=5.9 Hz, 1H), 4.06 (s, 3H), 3.71 (m, 1H), 3.54 (m, 1H), 1.35 (s, 11H).

G.iii. rac-(3-oxo-5,6-dihydro-3H-pyrrolo[1,2,3-de]quinoxalin-6-yl)-carbamic acid tert-butyl ester

(114) Starting from intermediate G.ii (4.47 g, 14 mmol) and following procedure H, the reaction mixture was refluxed in DCE (100 mL) for 3 days. The mixture was cooled to rt, diluted with DCM, washed with water, dried over MgSO.sub.4 and concentrated. The residue was crystallized from ether/EA to give a mixture of the desired intermediate and the corresponding oxazolidinone as an off-white solid (2.2 g) which was used in the next step without further purification or characterization.

G.iv. rac-6-amino-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

(115) A solution of intermediate G.iii (2.17 g, 3.8 mmol) in DCM (10 mL) was treated with TFA (5 mL). The mixture was stirred at rt for 1 h, concentrated in vacuo and partitioned between DCM and water. The org. phase containing impurities was discarded and the aq. phase basified with NH.sub.4OH and extracted several times with DCM/MeOH 9:1. The combined org. phases were dried over MgSO.sub.4 and concentrated to give the desired compound as an orange solid (0.36 g, 51% yield).

(116) .sup.1H NMR (DMSO-d.sub.6) δ: 8.17 (s, 1H), 7.67 (d, J=8.2 Hz, 1H), 7.58 (dt, J=7.3, 0.9 Hz, 1H), 7.32 (dd, J=7.9, 7.3 Hz, 1H), 4.77 (dd, J=8.5, 4.4 Hz, 1H), 4.50 (dd, J=13.2, 8.5 Hz, 1H), 3.86 (dd, J=13.2, 4.4 Hz, 1H).

Preparation H: methanesulfonic acid 2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethyl ester

H.i. tert-butyl-dimethyl-[(R)-2-oxiranyl-ethoxy]-silane and (2S)-4-(tert-butyl-dimethyl-silanyloxy)-butane-1,2-diol

(117) The title intermediates were prepared in analogy to Kishi et al., Org. Lett. (2005), 7, 3997, (intermediate S2-3) via hydrolytic kinetic resolution of (RS)-tert-butyl-dimethyl-(2-oxiranyl-ethoxy)-silane (prepared according to J. Org. Chem. (2008), 73, 1093). Two compounds were isolated after CC (Hept/EA 2:1).

(118) First eluting compound: tert-butyl-dimethyl-[(R)-2-oxiranyl-ethoxy]-silane (colourless oil, 25.3 g, 48% yield). .sup.1H NMR (CDCl.sub.3) δ: 3.77 (t, J=6.4 Hz, 2H), 3.04 (m, 1H), 2.78 (m, 1H), 2.51 (dd, J=5.0, 2.9 Hz, 1H), 1.74 (m, 2H), 0.90 (d, J=0.6 Hz, 9H), 0.06 (s, 6H).

(119) Second eluting compound: (2S)-4-(tert-butyl-dimethyl-silanyloxy)-butane-1,2-diol (colourless oil, 24.9 g, 43% yield). .sup.1H NMR (CDCl.sub.3) δ: 3.89 (m, 3H), 3.62 (s, 1H), 3.53 (m, 1H), 3.42 (br. s, 1H), 2.29 (m, 1H), 1.70 (m, 2H), 0.90 (s, 9H), 0.09 (s, 6H).

H.ii. Toluene-4-sulfonic acid (S)-4-(tert-butyl-dimethyl-silanyloxy)-2-hydroxy-butyl ester

(120) To a solution of (2S)-4-(tert-butyl-dimethyl-silanyloxy)-butane-1,2-diol (23.9 g, 108 mmol, second eluting compound in H.i and DMAP (2.65 g, 0.2 eq.) in DCM (80 mL) cooled to 0° C. were added TEA (43.8 mL, 2.9 eq.) and a solution of pTsCl (20.7 g, 1.1 eq.) in DCM (15 mL). The mixture was stirred at rt for 5 h, poured into sat. aq. NaHCO.sub.3 and extracted with DCM. The org. layer was dried over MgSO.sub.4 and concentrated. The residue was purified by CC (Hept/EA 2:1) to afford the title intermediate as a colourless oil (31.3 g, 77% yield).

(121) .sup.1H NMR (CDCl.sub.3) δ: 7.80 (d, J=7.6 Hz, 2H), 7.34 (d, J=7.6 Hz, 2H), 4.02 (m, 3H), 3.80 (m, 2H), 2.45 (s, 3H), 1.70 (m, 2H), 1.27 (m, 1H), 0.87 (s, 9H), 0.05 (s, 6H).

H.iii. (2S)-tert-butyl-dimethyl-(2-oxiranyl-ethoxy)-silane

(122) 2M NaOH (35 mL) was added to a solution of intermediate H.ii (31.1 g, 83.1 mmol) in THF (350 mL) and the resulting mixture was vigorously stirred at rt for 3 h. The mixture was taken in 1M NaOH (200 mL) and extracted with TBME (2×). The combined org. layers were washed with water and brine, dried over MgSO.sub.4 and concentrated. The resulting oil was purified by Kugelrohr-distillation (ca. 70° C. at 0.1 mbar) to afford the title intermediate as a colourless oil (14.7 g, 87% yield).

(123) .sup.1H NMR (CDCl.sub.3) δ: 3.77 (t, J=6.4 Hz, 2H), 3.04 (m, 1H), 2.78 (m, 1H), 2.51 (dd, J=5.0, 2.9 Hz, 1H), 1.74 (m, 2H), 0.90 (d, J=0.6 Hz, 9H), 0.06 (s, 6H).

H.iv. 6-[(S)-4-(tert-butyl-dimethyl-silanyloxy)-2-hydroxy-butylamino]-4H-benzo[1,4]oxazin-3-one

(124) A solution of 6-amino-4H-benzo[1,4]oxazin-3-one (5.03 g, 30.6 mmol; commercial) and intermediate H.iii (6.2 g, 1 eq.) in EtOH/H.sub.2O (9:1; 180 mL) was heated at 80° C. for 2 days. The mixture was concentrated under reduced pressure. Residual starting aniline could be removed by addition of Et.sub.2O/MeOH followed by filtration. The filtrate containing the product was concentrated under reduced pressure to afford the title intermediate as a brown oil (9.45 g, 84% yield) which was used as such in the next step.

(125) MS (ESI, m/z): 367.2 [M+H.sup.+].

H.v. 6-{(S)-5-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]oxazin-3-one

(126) Starting from intermediate H.iv (9.4 g, 25.6 mmol), and using procedure I, the title intermediate was obtained as a beige solid (2.40 g, 24% yield) after CC (DCM/MeOH/NH.sub.4OH 1000:50:4).

(127) MS (ESI, m/z): 393.4 [M+H.sup.+].

H.vi. 6-[(S)-5-(2-hydroxy-ethyl)-2-oxo-oxazolidin-3-yl]-4H-benzo[1,4]oxazin-3-one

(128) Starting from intermediate H.v (2.40 g, 6.11 mmol) and using procedure J, the title intermediate was obtained as an off-white solid (0.82 g, 48% yield) after trituration with Et.sub.2O/EA.

(129) MS (ESI, m/z): 279.5 [M+H.sup.+].

H.vii. Methanesulfonic acid 2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethyl ester

(130) Starting from intermediate H.vi (0.82 g, 2.95 mmol) and using procedure H, the title compound was obtained as a beige solid (0.61 g, 58% yield).

(131) .sup.1H NMR (DMSO-d6) δ: 10.72 (s, 1H), 7.30 (d, J=2.1 Hz, 1H), 6.93 (m, 2H), 4.76 (m, 1H), 4.52 (s, 2H), 4.34 (m, 2H), 4.11 (t, J=8.8 Hz, 1H), 3.72 (m, 1H), 3.20 (s, 3H), 2.17 (m, 2H).

(132) MS (ESI, m/z): 357.3 [M+H.sup.+].

Preparation I: methanesulfonic acid 2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethyl ester

I.i. 6-[(R)-4-(tert-butyl-dimethyl-silanyloxy)-2-hydroxy-butylamino]-4H-benzo[1,4]oxazin-3-one

(133) A solution of 6-amino-4H-benzo[1,4]oxazin-3-one (commercial; 6.49 g, 39.5 mmol) and tert-butyl-dimethyl-[(R)-2-oxiranyl-ethoxy]-silane (first eluting compound in step H.i; 8.0 g, 39.5 mmol) in EtOH/H.sub.2O (9:1; 240 mL) was heated at 80° C. for 2 days. The mixture was concentrated under reduced pressure. Residual starting aniline could be removed by addition of Et.sub.2O/MeOH followed by filtration. The filtrate containing the product was concentrated under reduced pressure and the residue was purified by CC (DCM/MeOH/NH.sub.4OH 1000:50:4) to afford the title intermediate as a brown oil (5.82 g, 40% yield).

(134) MS (ESI, m/z): 367.3 [M+H.sup.+].

I.ii. 6-{(R)-5-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]oxazin-3-one

(135) Starting from intermediate I.i (5.8 g, 15.8 mmol) and using procedure I, the title intermediate was obtained as a beige solid (2.7 g, 43% yield) after trituration with Et.sub.2O/EA/MeOH.

(136) MS (ESI, m/z): 393.5 [M+H.sup.+].

I.iii. 6-[(R)-5-(2-hydroxy-ethyl)-2-oxo-oxazolidin-3-yl]-4H-benzo[1,4]oxazin-3-one

(137) Starting from intermediate I.ii (2.70 g, 6.88 mmol) and using procedure J, the title intermediate was obtained as an off-white solid (1.25 g, 65% yield) after trituration with Et.sub.2O/MeOH.

(138) MS (ESI, m/z): 279.5 [M+H.sup.+].

I.iv. Methanesulfonic acid 2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethyl ester

(139) Starting from intermediate I.iii (2.1 g, 7.55 mmol) and using procedure H, the title compound was obtained as an off-white solid (1.16 g, 43% yield).

(140) MS (ESI, m/z): 357.2 [M+H.sup.+].

Preparation J: methanesulfonic acid 2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethyl ester

J.i. 6-[(R)-4-(tert-butyl-dimethyl-silanyloxy)-2-hydroxy-butylamino]-4H-benzo[1,4]thiazin-3-one

(141) A solution of 6-amino-4H-benzo[1,4]thiazin-3-one (10.68 g, 59.3 mmol; commercial) and tert-butyl-dimethyl-[(R)-2-oxiranyl-ethoxy]-silane (first eluting compound in step H.i.; 12.0 g, 59.3 mmol) in EtOH/H.sub.2O (9:1; 320 mL) was heated at 80° C. for 2 days. The mixture was concentrated under reduced pressure. Residual starting aniline could be removed by addition of Et.sub.2O/MeOH followed by filtration. The filtrate containing the product was concentrated under reduced pressure to afford the title intermediate as a brown oil (18.8 g, 83% yield) which was used as such in the next step.

(142) MS (ESI, m/z): 383.2 [M+H.sup.+].

J.ii. 6-{(R)-5-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]thiazin-3-one

(143) Starting from intermediate J.i (23.5 g, 49.1 mmol) and using procedure I, the title intermediate was obtained as a colourless solid (8.4 g, 42% yield) after CC (DCM/MeOH/NH.sub.4OH 1000:50:4).

(144) MS (ESI, m/z): 409.3 [M+H.sup.+].

J.iii. 6-[(R)-5-(2-hydroxy-ethyl)-2-oxo-oxazolidin-3-yl]-4H-benzo[1,4]thiazin-3-one

(145) Starting from intermediate J.ii (8.4 g, 20.6 mmol) and using procedure J, the title intermediate was obtained as an off-white solid (4.79 g, 79% yield) after trituration with Et.sub.2O/EA.

(146) MS (ESI, m/z): 295.5 [M+H.sup.+].

J.iv. Methanesulfonic acid 2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethyl ester

(147) Starting from intermediate J.iii (4.7 g, 16.0 mmol) and using procedure H, the title compound was obtained as an off-white solid (5.80 g, 98% yield) after CC (DCM/MeOH/NH.sub.4OH 1000:50:4).

(148) MS (ESI, m/z): 373.4 [M+H.sup.+].

Preparation K: 6-[(S)-5-(2-iodo-ethyl)-2-oxo-oxazolidin-3-yl]-4H-benzo[1,4]thiazin-3-one

K.i. 6-[(S)-4-(tert-butyl-dimethyl-silanyloxy)-2-hydroxy-butylamino]-4H-benzo[1,4]thiazin-3-one

(149) A solution of 6-amino-4H-benzo[1,4]thiazin-3-one (8.0 g, 44.5 mmol; commercial) and intermediate H.iii (9.0 g, 1 eq.) in 9-1 EtOH/H.sub.2O (250 mL) was heated at 80° C. for 2 days. The mixture was concentrated under reduced pressure. Residual starting aniline could be removed by addition of Et.sub.2O/MeOH followed by filtration. The filtrate containing the product was concentrated under reduced pressure to afford the title intermediate as a brown oil (14.58 g, 86% yield) which was used as such in the next step.

(150) MS (ESI, m/z): 383.2 [M+H.sup.+].

K.ii. 6-{(S)-5-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]thiazin-3-one

(151) Starting from intermediate K.i (14.5 g, 37.9 mmol) and using procedure I, the title intermediate was obtained as a colourless solid (5.56 g, 36% yield) after CC (DCM/MeOH/NH.sub.4OH 1000:50:4).

(152) MS (ESI, m/z): 409.3 [M+H.sup.+].

K.iii. 6-[(S)-5-(2-hydroxy-ethyl)-2-oxo-oxazolidin-3-yl]-4H-benzo[1,4]thiazin-3-one

(153) Starting from intermediate K.ii (5.50 g, 13.6 mmol) and using procedure J, the title intermediate was obtained as an off-white solid (3.08 g, 77% yield) after trituration with Et.sub.2O/EA.

(154) MS (ESI, m/z): 295.5 [M+H.sup.+].

K.iv. Methanesulfonic acid 2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethyl ester

(155) Starting from intermediate K.iii (3.0 g, 10.2 mmol) and using procedure H, the title intermediate was obtained as an off-white solid (3.64 g, 96% yield) after trituration with ether.

(156) MS (ESI, m/z): 373.4 [M+H.sup.+].

K.v. 6-[(S)-5-(2-iodo-ethyl)-2-oxo-oxazolidin-3-yl]-4H-benzo[1,4]thiazin-3-one

(157) Starting from intermediate K.iv (2.5 g, 6.7 mmol) and using procedure K, the title compound was obtained as a slightly orange solid (2.11 g, 78% yield) after trituration with Et.sub.2O/EA.

(158) .sup.1H NMR (DMSO-d6) δ: 10.55 (s, 1H), 7.30 (m, 2H), 7.04 (dd, J=8.5, 2.3 Hz, 1H), 4.68 (m, 1H), 4.10 (t, J=8.8 Hz, 1H), 3.70 (dd, J=8.8, 6.7 Hz, 1H), 3.41 (s, 2H), 3.29 (m, 2H), 2.23 (m, 2H).

Preparation L: 6-[(R)-5-(2-iodo-ethyl)-2-oxo-oxazolidin-3-yl]-4H-benzo[1,4]thiazin-3-one

(159) Starting from intermediate J.iv (3.5 g, 9.4 mmol) and using procedure K, the title compound was obtained as an off-white solid (3.52 g, 93% yield) after trituration with Et.sub.2O/EA.

(160) .sup.1H NMR (DMSO-d6) δ: 10.55 (s, 1H), 7.30 (m, 2H), 7.04 (dd, J=8.5, 2.3 Hz, 1H), 4.68 (m, 1H), 4.10 (t, J=8.8 Hz, 1H), 3.70 (dd, J=8.8, 6.7 Hz, 1H), 3.41 (s, 2H), 3.29 (m, 2H), 2.23 (m, 2H).

(161) MS (ESI, m/z): 405.0 [M+H.sup.+].

Preparation M: (RS)-methanesulfonic acid 2-[2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethyl ester

M.i. (RS)-6-[4-(tert-butyl-dimethyl-silanyloxy)-2-hydroxy-butylamino]-4H-benzo[1,4]thiazin-3-one

(162) A solution of 6-amino-4H-benzo[1,4]thiazin-3-one (3.56 g, 19.8 mmol; commercial) and (RS)-tert-butyl-dimethyl-(2-oxiranyl-ethoxy)-silane (prepared according to J. Org. Chem. (2008), 73, 1093; 4.0 g, 19.8 mmol) in EtOH/H.sub.2O (9:1; 140 mL) was heated at 80° C. for 2 days. The mixture was concentrated under reduced pressure and the residue was purified by CC (DCM/MeOH/NH.sub.4OH 1000:50:4) to afford the title intermediate as a brown oil (2.20 g, 29% yield).

(163) MS (ESI, m/z): 383.2 [M+H.sup.+].

M.ii. (RS)-6-{5-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]thiazin-3-one

(164) Starting from intermediate M.i (2.20 g, 5.75 mmol) and using procedure I, the title intermediate was obtained as a pale orange solid (1.53 g, 65% yield) after CC (DCM/MeOH/NH.sub.4OH 1000:50:4).

(165) MS (ESI, m/z): 409.4 [M+H.sup.+].

M.iii. (RS)-6-[5-(2-hydroxy-ethyl)-2-oxo-oxazolidin-3-yl]-4H-benzo[1,4]thiazin-3-one

(166) Starting from intermediate M.ii (1.50 g, 3.67 mmol) and using procedure J, the title intermediate was obtained as an off-white solid (0.73 g, 68% yield) after trituration with Et.sub.2O/EA.

(167) MS (ESI, m/z): 295.1 [M+H.sup.+].

M.iv. (RS)-methanesulfonic acid 2-[2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethyl ester

(168) Starting from intermediate M.iii (0.70 g, 2.38 mmol) and using procedure H, the title compound was obtained as a beige solid (0.80 g, 90% yield) after CC (DCM/MeOH/NH.sub.4OH 1000:50:4).

(169) MS (ESI, m/z): 373.1 [M+H.sup.+].

Preparation N: 6-((S)-5-iodomethyl-2-oxo-oxazolidin-3-yl)-4H-benzo[1,4]thiazin-3-one

N.i. 6-((S)-3-chloro-2-hydroxy-propylamino)-4H-benzo[1,4]thiazin-3-one

(170) A suspension of 6-amino-4H-benzo[1,4]thiazin-3-one (18.0 g, 100 mmol; commercial) and Ca(OTf).sub.2 (0.5 eq.) in MeCN (800 mL) was heated at 500 for 1 h. (S)-epichlorohydrin (18.5 g, 200 mmol) was added and the mixture was stirred at rt for 72 h and at 45° C. for 24 h. The volatiles were removed under reduced pressure. After aqueous workup and extraction with EA, the title intermediate crystallised from EA to afford a beige solid (17.38 g, 64% yield).

(171) MS (ESI, m/z): 273.2 [M+H.sup.+].

N.ii. 6-((S)-5-chloromethyl-2-oxo-oxazolidin-3-yl)-4H-benzo[1,4]thiazin-3-one

(172) Starting from intermediate N.i (39.3 g, 144 mmol.) and using procedure I, the title intermediate was obtained as a beige solid (34.2 g, 79% yield) after CC (EA/Hept 2:1, EA).

(173) MS (ESI, m/z): 299.1 [M+H.sup.+].

N.iii. 6-((S)-5-iodomethyl-2-oxo-oxazolidin-3-yl)-4H-benzo[1,4]thiazin-3-one

(174) Starting from intermediate N.ii (14.0 g, 46.9 mmol) and using procedure K, the title compound was obtained as a pale beige solid (15.0 g, 82% yield).

(175) .sup.1H NMR (DMSO-d6) δ: 10.56 (s, 1H), 7.31 (m, 2H), 7.12 (dd, J=8.5, 2.3 Hz, 1H), 4.71 (m, 1H), 4.14 (t, J=9.1 Hz, 1H), 3.59 (m, 3H), 3.31 (s, 2H).

(176) MS (ESI, m/z): 391.4 [M+H.sup.+].

Preparation O: 6-((R)-5-iodomethyl-2-oxo-oxazolidin-3-yl)-4H-benzo[1,4]thiazin-3-one

O.i. 6-((R)-3-chloro-2-hydroxy-propylamino)-4H-benzo[1,4]thiazin-3-one

(177) A solution of 6-amino-4H-benzo[1,4]thiazin-3-one (18.39 g, 102 mmol; commercial) and (R)-epichlorohydrin (8.0 mL, 1 eq.) in EtOH/H.sub.2O (9:1; 450 mL) was heated at 80° C. overnight. The mixture was concentrated under reduced pressure. Residual starting aniline could be removed by addition of Et.sub.2O/EA followed by filtration. The filtrate containing the product was concentrated under reduced pressure to afford the title intermediate as a beige solid (22.52 g, 81% yield) which was used as such in the next step.

(178) MS (ESI, m/z): 273.2 [M+H.sup.+].

O.ii. 6-((R)-5-chloromethyl-2-oxo-oxazolidin-3-yl)-4H-benzo[1,4]thiazin-3-one

(179) Starting from intermediate O.i (22.0 g, 81.0 mmol) and using procedure I, the title intermediate was obtained as a yellow solid (8.79 g, 36% yield) after trituration with DCM/MeOH.

(180) MS (ESI, m/z): 299.1 [M+H.sup.+].

O.iii. 6-((R)-5-iodomethyl-2-oxo-oxazolidin-3-yl)-4H-benzo[1,4]thiazin-3-one

(181) Starting from intermediate O.ii (8.75 g, 29 mmol) and using procedure K, the title compound was obtained as an off-white solid (9.27 g, 81% yield) after trituration with Et.sub.2O/EA.

(182) .sup.1H NMR (DMSO-d6) δ: 10.56 (s, 1H), 7.31 (m, 2H), 7.12 (dd, J=8.5, 2.3 Hz, 1H), 4.71 (m, 1H), 4.14 (t, J=9.1 Hz, 1H), 3.59 (m, 3H), 3.31 (s, 2H).

(183) MS (ESI, m/z): 390.9 [M+H.sup.+].

Preparation P: (S)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-5-iodomethyl-oxazolidin-2-one

P.i. (S)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-5-hydroxymethyl-oxazolidin-2-one

(184) A solution of (2,3-dihydro-benzo[1,4]dioxin-6-yl)-carbamic acid benzyl ester (13.0 g, 45.6 mmol) in THF (220 mL) was cooled to −78° C. before the dropwise addition of n-BuLi (29.5 mL of a 2.3M solution in Hex, 1.1 eq.). The mixture was stirred at −78° C. for 1 h and then warmed to −15° C. and treated dropwise with (S)-glycidyl butyrate (7.37 g, 1.1 eq.). The mixture was stirred at rt overnight. Cs.sub.2CO.sub.3 (tip of a spatula) was added and the mixture heated at 40° C. until complete conversion. The mixture was diluted with EA and washed with a sat. aq. NH.sub.4Cl and water. The org. layer was dried over MgSO.sub.4 and concentrated. The residue was purified by CC (Hex/EA 2:1, 1:1) to afford the title intermediate as a grey solid (7.04 g, 62% yield).

(185) .sup.1H NMR (DMSO-d6) δ: 7.13 (d, J=2.5 Hz, 1H), 6.96 (dd, J=2.5, 8.9 Hz, 1H), 6.86 (d, J=8.9 Hz, 1H), 5.16 (t, J=5.8 Hz, 1H), 4.70-4.50 (m, 1H), 4.30-4.10 (m, 4H), 4.10-3.90 (m, 1H), 4.80-4.70 (m, 1H), 4.70-4.60 (m, 1H), 4.60-4.50 (m, 1H).

P.ii. Methanesulfonic acid (S)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-ylmethyl ester

(186) Starting from intermediate P.i (7.0 g, 27.9 mmol) and using procedure H, the title intermediate was obtained as a colourless solid (9.0 g, 98% yield).

(187) MS (ESI, m/z): 330.3 [M+H.sup.+].

P.iii. (S)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-5-iodomethyl-oxazolidin-2-one

(188) Starting from intermediate P.ii (9.0 g, 27.3 mmol) and using procedure K, the title compound was obtained as an off-white solid (6.91 g, 70% yield) after trituration with Et.sub.2O/EA.

(189) .sup.1H NMR (CDCl.sub.3) δ: 7.07 (d, J=2.6 Hz, 1H), 6.98 (dd, J=9.1, 2.6 Hz, 1H), 6.85 (d, J=8.9 Hz, 1H), 4.68 (m, 1H), 4.24 (s, 4H), 4.10 (t, J=9.1 Hz, 1H), 3.72 (dd, J=9.1, 5.9 Hz, 1H), 3.46 (m, 1H), 3.33 (m, 1H).

(190) MS (ESI, m/z): 362.2 [M+H.sup.+].

Preparation Q: methanesulfonic acid (S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-ylmethyl ester

Q.i. 6-[(S)-3-(tert-butyl-dimethyl-silanyloxy)-2-hydroxy-propylamino]-4H-benzo[1,4]oxazin-3-one

(191) LiClO.sub.4 (7.20 g, 3 eq.) was added to a solution of tert-butyl-dimethyl-((S)-1-oxiranylmethoxy)-silane (commercial; 4.25 g, 22.6 mmol) in MeCN (70 mL). 6-amino-4H-benzo[1,4]oxazin-3-one (commercial; 3.70 g, 1 eq.) was then added and the mixture was stirred at 50° C. for 6 h. The solvent was removed under reduced pressure and the residue was purified by CC (DCM/MeOH/NH.sub.4OH 1000/25/2) to afford the title intermediate as a pale brown foam (5.25 g, 66% yield).

(192) MS (ESI, m/z): 353.3 [M+H.sup.+].

Q.ii. 6-[(S)-5-(tert-butyl-dimethyl-silanyloxymethyl)-2-oxo-oxazolidin-3-yl]-4H-benzo[1,4]oxazin-3-one

(193) Starting from intermediate Q.i (10.24 g, 29 mmol) and using procedure I, the title intermediate was obtained as a pale yellow solid (6.30 g, 57% yield) after trituration with ether.

(194) MS (ESI, m/z): 379.2 [M+H.sup.+].

Q.iii. 6-((S)-5-hydroxymethyl-2-oxo-oxazolidin-3-yl)-4H-benzo[1,4]oxazin-3-one

(195) Starting from intermediate Q.ii (6.30 g, 16.6 mmol) and using procedure J, the title intermediate was obtained as a colourless solid (3.49 g, 79% yield) after trituration with EA.

(196) MS (ESI, m/z): 265.5 [M+H.sup.+].

Q.iv. Methanesulfonic acid (S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-ylmethyl ester

(197) A suspension of intermediate Q.iii (4.93 g, 18.7 mmol) in anhydrous DCM (110 mL) was treated with DIPEA (12.0 mL, 3.75 eq.) and the mixture was cooled to 0° C. Ms.sub.2O (4.88 g, 1.5 eq.) was added portionwise. The resulting mixture was stirred at 0° C. for 15 min. Water was added and stirring was continued for 15 min at rt. The precipitated product was filtered, washed with water and DCM. The thus obtained solid was triturated with DCM/MeOH/NH.sub.4OH (1000:25:2) to give the title intermediate as a colourless solid (3.785 g, 60% yield).

(198) .sup.1H NMR (DMSO-d6) δ: 10.72 (s, 1H), 7.29 (dd, J=2.1, 0.6 Hz, 1H), 6.94 (m, 2H), 4.95 (m, 1H), 4.52 (s, 2H), 4.49 (m, 2H), 4.11 (t, J=9.1 Hz, 1H), 3.73 (m, 2H), 3.23 (s, 3H).

(199) MS (ESI, m/z): 343.3 [M+H.sup.+].

Preparation R: (S)-3-(3-fluoro-4-methyl-phenyl)-5-iodomethyl-oxazolidin-2-one

R.i. (S)-3-(3-fluoro-4-methyl-phenyl)-5-hydroxymethyl-oxazolidin-2-one

(200) A mixture of 3-fluoro-4-methyl-aniline (commercial; 1.25 g, 10 mmol), sat. aq. NaHCO.sub.3 (10 mL) and acetone (10 mL) was treated dropwise with benzyl chloroformate (1.70 g, 1.41 mL, 1 eq.). After CO.sub.2 evolution ceased, the mixture was partitioned between EA and sat. aq. NaHCO.sub.3, the org. layer was dried over MgSO.sub.4 and concentrated under reduced pressure. The resulting benzyl carbamate was dissolved in THF (50 mL) and cooled under argon to −78° C. n-BuLi (2.5M in Hex, 6.45 mL, 1.1 eq.) was added dropwise, and the resulting solution was stirred for 1 h at that temperature. The reaction was then allowed to warm to −15° C. at which (S)-glycidyl butyrate (1.69 mL, 1.1 eq.) was added dropwise. The mixture was stirred at rt overnight. A tip of a spatula of Cs.sub.2CO.sub.3 was added, and the mixture was stirred at rt for 3 h. NH.sub.4Cl and EA were added and the phases were separated. The aq. phase was extracted once more with EA and the combined org. extracts were washed several times with sat. aq. NH.sub.4Cl, then with brine, dried over Na.sub.2SO.sub.4 and concentrated. The orange solid obtained was triturated with EA to afford the title intermediate as a pale yellow solid (1.18 g, 53% yield).

(201) MS (ESI, m/z): 226.3 [M+H*].

R.ii. Methanesulfonic acid (S)-3-(3-fluoro-4-methyl-phenyl)-2-oxo-oxazolidin-5-ylmethyl ester

(202) Starting from intermediate R.i (4.70 g, 20.9 mmol) and following procedure H the title intermediate was obtained as a yellow solid (6.37 g, 100% yield) after trituration in ether.

(203) .sup.1H NMR (CDCl.sub.3) δ: 7.36 (dd, J=11.7, 2.3 Hz, 1H), 7.13 (m, 2H), 4.91 (m, 1H), 4.46 (m, 2H), 4.13 (t, J=9.1 Hz, 1H), 3.92 (dd, J=9.1, 6.2 Hz, 1H), 3.10 (s, 3H), 2.25 (d, J=1.8 Hz, 3H).

(204) MS (ESI, m/z): 330.3 [M+H.sup.+].

R.iii. (S)-3-(3-fluoro-4-methyl-phenyl)-5-iodomethyl-oxazolidin-2-one

(205) Starting from intermediate R.ii (6.30 g, 20.8 mmol) and using procedure K, the title compound was obtained as a slightly pink solid (6.3 g, 91% yield) after trituration with Et.sub.2O/EA.

(206) .sup.1H NMR (CDCl.sub.3) δ: 7.36 (dd, J=12.0, 2.1 Hz, 1H), 7.16 (m, 2H), 4.73 (m, 1H), 4.14 (m, 1H), 3.76 (dd, J=9.4, 6.2 Hz, 1H), 3.48 (m, 1H), 3.35 (dd, J=10.3, 8.2 Hz, 1H), 2.25 (d, J=1.8 Hz, 3H).

(207) MS (ESI, m/z): 335.8 [M+H.sup.+].

Preparation S: (RS)-methanesulfonic acid 2-[3-(3-fluoro-4-methyl-phenyl)-2-oxo-oxazolidin-5-yl]-ethyl ester

S.i. (RS)-4-(tert-butyl-dimethyl-silanyloxy)-1-(3-fluoro-4-methyl-phenylamino)-butan-2-ol

(208) To a solution of (RS)-tert-butyl-dimethyl-(2-oxiranyl-ethoxy)-silane (4.4 g, 200 mmol; prepared as in J. Org. Chem. (2008), 73, 1093) in MeCN (60 mL) was added LiClO.sub.4 (6.31 g, 3 eq.). 3-fluoro-4-methylaniline (commercial; 2.28 g, 0.92 eq.) was added and the mixture was stirred at 50° C. for 5 h. The solvent was removed under reduced pressure and the residue was purified by CC (DCM/MeOH/NH.sub.4OH 1000:25:2) to afford the title intermediate as a brown oil (5.56 g, 86% yield).

(209) MS (ESI, m/z): 328.4 [M+H.sup.+].

S.ii. (RS)-5-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-3-(3-fluoro-4-methyl-phenyl)-oxazolidin-2-one

(210) Starting from intermediate S.i (2.50 g, 7.63 mmol) and using procedure I, the title intermediate was obtained as an off-white solid (1.22 g, 45% yield) after trituration with ether/EA.

(211) MS (ESI, m/z): 354.2 [M+H.sup.+].

S.iii. (RS)-3-(3-fluoro-4-methyl-phenyl)-5-(2-hydroxy-ethyl)-oxazolidin-2-one

(212) Starting from intermediate S.ii (1.20 g, 3.40 mmol) and using procedure J, the title intermediate was obtained as a colourless solid (0.478 g, 59% yield) after trituration with Et.sub.2O/EA/DCM.

(213) MS (ESI, m/z): 240.1 [M+H.sup.+].

S.iv. (RS)-methanesulfonic acid 2-[3-(3-fluoro-4-methyl-phenyl)-2-oxo-oxazolidin-5-yl]-ethyl ester

(214) Starting from intermediate S.iii (470 mg, 2.0 mmol) and using procedure H, the title compound was obtained as an off-white solid (0.60 g, 96% yield) after CC (DCM/MeOH/NH.sub.4OH 1000:50:4).

(215) MS (ESI, m/z): 318.2 [M+H.sup.+].

Preparation T: 3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propionaldehyde

T.i. 6-[(R)-5-(tert-butyl-dimethyl-silanyloxy)-2-hydroxy-pentylamino]-4H-benzo[1,4]oxazin-3-one

(216) A mixture of (R)-tert-butyl-dimethyl-(3-oxiranyl-propoxy)-silane (13 g, 60 mmol; prepared according to Org. Lett. (2005), 7, 3997) and 6-amino-4H-benzo[1,4]oxazin-3-one (9.9 g) in EtOH/H.sub.2O (9:1, 325 mL) was heated at reflux overnight. The volatiles were removed under reduced pressure and the residue purified by CC (Hept/EA 1:1) to give the desired intermediate as a brown oil (8.9 g, 39% yield).

(217) MS (ESI, m/z): 318.2 [M+H.sup.+].

T.ii. 6-{(R)-5-[3-(tert-butyl-dimethyl-silanyloxy)-propyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]oxazin-3-one

(218) Starting from intermediate T.i (8.8 g, 23 mmol) and using procedure I, the title intermediate was obtained as an orange solid (9.8 g, quant.) after crystallisation from Hept/EA.

(219) MS (ESI, m/z): 407.6 [M+H.sup.+].

T.iii. 6-[(R)-5-(3-hydroxy-propyl)-2-oxo-oxazolidin-3-yl]-4H-benzo[1,4]thiazin-3-one

(220) Starting from intermediate T.ii (9.8 g, 24 mmol) and using procedure J, the title intermediate was obtained as a yellowish solid (5.0 g, 71% yield) after CC (EA, EA/MeOH 9:1) followed by crystallisation from ether/EA.

(221) MS (ESI, m/z): 293.3 [M+H.sup.+].

T.iv. 3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propionaldehyde

(222) To a solution of intermediate T.iii (292 mg, 1 mmol) and DIPEA (0.5 mL, 3 eq.) in DCM (5 mL) at rt was added dropwise a solution of SO.sub.3.pyridine complex (318 mg, 2 eq.) in DMSO (1 mL) over 10 min. The mixture was stirred at rt for 2 h, diluted with DCM and washed with water. The org. phase was washed several times with water, dried over MgSO.sub.4 and concentrated to give the desired aldehyde as a beige solid (260 mg, 90% yield).

(223) .sup.1H NMR (DMSO-d6) δ: 10.71 (s, 1H) 9.68 (d, J=0.9 Hz, 1H), 7.31 (s, 1H), 6.92 (m, 2H), 4.64 (m, 1H), 4.52 (d, J=1.2 Hz, 2H), 4.07 (m, 1H), 3.66 (m, 1H), 2.60 (m, 2H), 1.98 (m, 2H).

Preparation U: 3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propionaldehyde

U.i. 6-[(R)-5-(tert-butyl-dimethyl-silanyloxy)-2-hydroxy-pentylamino]-4H-benzo[1,4]thiazin-3-one

(224) A mixture of (R)-tert-butyl-dimethyl-(3-oxiranyl-propoxy)-silane (13 g, 60 mmol; prepared as in Org. Lett. (2005), 7, 3997) and 6-amino-4H-benzo[1,4]thiazin-3-one (10.8 g) in EtOH/H.sub.2O (9:1, 325 mL) was heated at reflux overnight. The volatiles were removed under reduced pressure and the residue purified by CC (Hept/EA 1:1) to give the desired intermediate as a brown oil (6.8 g, 28% yield).

(225) MS (ESI, m/z): 397.1 [M+H.sup.+].

U.ii. 6-{(R)-5-[3-(tert-butyl-dimethyl-silanyloxy)-propyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]thiazin-3-one

(226) Starting from intermediate U.i (6.7 g, 17 mmol) and using procedure I, the title intermediate was obtained as an orange solid (7.8 g, quant.) after crystallisation from Hept/EA.

(227) MS (ESI, m/z): 423.4 [M+H.sup.+].

U.iii. 6-[(R)-5-(3-hydroxy-propyl)-2-oxo-oxazolidin-3-yl]-4H-benzo[1,4]thiazin-3-one

(228) Starting from intermediate U.ii (7.1 g, 16.8 mmol) and using procedure J, the title intermediate was obtained as a yellowish solid (3.1 g, 60% yield) after CC (EA. EA/MeOH 9:1).

(229) MS (ESI, m/z): 309.1 [M+H.sup.+].

U.iv. 3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propionaldehyde

(230) To a solution of intermediate U.iii (500 mg, 1.6 mmol) and DIPEA (0.83 mL, 3 eq.) in DCM (7 mL) at rt was added dropwise a solution of SO.sub.3.pyridine complex (516 mg, 2 eq.) in DMSO (1.7 mL) over 10 min. The mixture was stirred at rt for 2 h, diluted with DCM and washed with water. The org. phase was washed several times with water, dried over MgSO.sub.4 and concentrated to give the desired aldehyde after trituration with ether/EA as a beige solid (440 mg, 88% yield).

(231) MS (ESI, m/z): 307.5 [M+H.sup.+].

Preparation V: (R)-4-aminomethyl-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

V.i. 2-(6-methoxy-[1,5]naphthyridin-4-yl)-propane-1,3-diol

(232) A mixture of 2-methoxy-8-methyl-[1,5]naphthyridine (2.90 g, 16.6 mmol; prepared according to WO 00/21948) and formaldehyde (37% in water, 7.8 mL) was heated at 100° C. for 3 days and at 110° C. for 2 days. After cooling to rt, the mixture was concentrated, taken up in MeOH and concentrated again. The residue was purified by CC (DCM/MeOH/NH.sub.4OH 1000:100:8) to afford the title intermediate as a pale beige solid (2.78 g, 71% yield).

(233) .sup.1H NMR (DMSO-d.sub.6) δ: 8.67 (d, J=4.4 Hz, 1H), 8.22 (d, J=9.1 Hz, 1H), 7.51 (d, J=4.4 Hz, 1H), 7.22 (d, J=9.1 Hz, 1H), 4.56 (m, 2H), 4.00 (s, 3H), 3.84 (m, 3H).

V.ii. Acetic acid (S)-3-hydroxy-2-(6-methoxy-[1,5]naphthyridin-4-yl)-propyl ester

(234) A 0.5M solution of intermediate V.i (5.45 g, 23.3 mmol) in vinyl acetate (60 mL) was treated with powdered 3 Å molecular sieves (350 mg) and stirred at rt for 15 min under a nitrogen atmosphere. Lipase from Candida antarctica (2.69 g, bound to acrylic resin) was added and stirring was continued for 4 h at rt. The mixture was filtered; the filter cake was washed with EA and the filtrate was concentrated. The residue was purified by CC (DCM/MeOH/NH.sub.4OH 1000:25:2) to afford the title intermediate as a colourless oil (2.70 g, 42% yield). The corresponding diacetate (3.81 g, 51% yield) was then afterwards cleaved back to the diol and used again as substrate.

(235) .sup.1H NMR (CDCl.sub.3) δ: 8.72 (d, J=4.4 Hz, 1H), 8.23 (d, J=9.1 Hz, 1H), 7.46 (d, J=4.4 Hz, 1H), 7.14 (d, J=9.1 Hz, 1H), 4.65 (m, 2H), 4.22 (m, 1H), 4.07 (m, 4H), 2.96 (m, 1H), 2.04 (s, 1H).

(236) MS (ESI, m/z): 277.3 [M+H.sup.+].

(237) Alternative α:

V.iii. Acetic acid (S)-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de][1,5]naphthyridin-4-ylmethyl ester

(238) TEA (2.1 mL, 2 eq.) and MsCl (0.70 mL, 1.2 eq.) were added at 0° C. to a solution of intermediate V.ii (2.05 g, 7.41 mmol) in DCM (40 mL). The reaction was stirred for 20 min at this temperature. DCE (40 mL) was added and the solution was slowly warmed to 60° C. and let stir at this temperature for 4 h. After cooling to rt, water was added and the two layers were decanted and the aq. layer was extracted once more with DCM. The combined org. layers were concentrated to dryness. The residue was triturated with TBME to afford the title intermediate as a grey solid (1.40 g, 77% yield).

(239) .sup.1H NMR (CDCl.sub.3) δ: 8.52 (d, J=4.7 Hz, 1H), 7.93 (d, J=9.7 Hz, 1H), 7.34 (d, J=4.7 Hz, 1H), 6.89 (d, J=9.7 Hz, 1H), 4.56 (dd, J=12.9, 9.4 Hz, 1H), 4.36 (m, 2H), 4.27 (dd, J=13.2, 5.0 Hz, 1H), 4.10 (m, 1H), 2.06 (s, 3H).

(240) MS (ESI, m/z): 245.2 [M+H.sup.+].

V.iv. (S)-4-hydroxymethyl-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(241) K.sub.2CO.sub.3 (0.40 g, 0.5 eq.) was added to a solution of intermediate V.iii (1.40 g, 5.73 mmol) cooled to 0° C. and the resulting mixture was vigorously stirred at 0° C. for 30 min. The mixture was concentrated and the residue was purified by CC (DCM/MeOH/NH.sub.4OH 1000:100:8). The product was triturated with EA/TBME to afford the title intermediate as a grey solid (0.98 g, 85% yield).

(242) MS (ESI, m/z): 203.0 [M+H.sup.+].

V.v. Methanesulfonic acid (S)-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de][1,5]naphthyridin-4-ylmethyl ester

(243) A solution of intermediate V.iv (0.33 g, 1.63 mmol) and TEA (0.57 mL, 2.5 eq.) in anhydrous DCM (15 mL) was cooled to 0° C. and treated dropwise with MsCl (0.19 mL, 1.5 eq.). The resulting mixture was stirred at 0° C. for 1 h. Water and DCM were added and the phases separated. The org. layer was dried over MgSO.sub.4 and concentrated under reduced pressure to afford the title intermediate as a colourless gum (0.40 g, 88% yield) which was used in the next step without further purification.

(244) MS (ESI, m/z): 281.3 [M+H.sup.+].

V.vi. (R)-4-aminomethyl-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(245) A solution of intermediate V.v (0.35 g, 1.24 mmol) in DMF (12 mL) was treated with sodium azide (0.65 g, 8 eq.) and stirred at 50° C. for 1.5 h. After cooling to rt, water was added and the mixture was extracted with DCM. The org. layer was dried over MgSO.sub.4 and concentrated under reduced pressure to give a yellow oil (crude azide) which was taken up in THF (1.5 mL). PPh.sub.3 (390 mg) and water (0.13 mL) were added and the mixture was heated at 50° C. for 3 h. The reaction mixture was concentrated to dryness and the residue was purified by CC (DCM/MeOH/NH.sub.4OH 1000:100:8) to afford the title intermediate as a yellow oil (30 mg, 12% yield).

(246) MS (ESI, m/z): 202.2 [M+H.sup.+].

(247) Alternative β:

V.ii. Acetic acid (R)-3-(tert-butyl-dimethyl-silanyloxy)-2-(6-methoxy-[1,5]naphthyridin-4-yl)-propyl ester

(248) To a solution of intermediate V.ii (1.66 g) in DCM (50 mL) were added imidazole (1 eq.) and TBDMSCl (1 eq.). The mixture was stirred at rt for 3 h. Another eq. of each reagent was added and the reaction was complete after 15 min. Water was added and the mixture was extracted with DCM. The org. layer was dried over MgSO.sub.4 and concentrated to afford the title intermediate as a colourless oil (2.36 g, 100% yield).

(249) MS (ESI, m/z): 391.5 [M+H.sup.+].

V.iii. (R)-3-(tert-butyl-dimethyl-silanyloxy)-2-(6-methoxy-[1,5]naphthyridin-4-yl)-propan-1-ol

(250) A suspension of intermediate V.vii (2.36 g) and K.sub.2CO.sub.3 (3.34 g) in MeOH (50 mL) was vigorously stirred at rt for 30 min. Water and DCM were added. The two layers were decanted and the aq. layer was extracted once more with DCM. The combined org. layers were dried over MgSO.sub.4, filtered and concentrated to dryness to afford the title intermediate as a colourless oil (2.1 g, 100% yield).

(251) MS (ESI, m/z): 349.1 [M+H.sup.+].

V.ix. 8-[(R)-2-azido-1-(tert-butyl-dimethyl-silanyloxymethyl)-ethyl]-2-methoxy-[1,5]naphthyridine

(252) Starting from intermediate V.viii (2.09 g) and following procedure N, the title intermediate was isolated as a colourless oil (1.79 g, 80% yield).

(253) MS (ESI, m/z): 374.1 [M+H.sup.+].

V.x. [(R)-3-(tert-butyl-dimethyl-silanyloxy)-2-(6-methoxy-[1,5]naphthyridin-4-yl)-propyl]-carbamic acid tert-butyl ester

(254) Starting from intermediate V.ix (1.79 g) and using procedure F and procedure G, the title intermediate was obtained as a dark oil (2.14 g, 100% yield).

(255) MS (ESI, m/z): 448.2 [M+H.sup.+].

V.xi. [(R)-3-hydroxy-2-(6-methoxy-[1,5]naphthyridin-4-yl)-propyl]-carbamic acid tert-butyl ester

(256) Starting from intermediate V.x (2.14 g) and using procedure J, the title intermediate was obtained as a colourless solid (1.14 g, 72% yield).

(257) MS (ESI, m/z): 334.2 [M+H.sup.+].

V.xii. ((R)-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de][1,5]naphthyridin-4-ylmethyl)-carbamic acid tert-butyl ester

(258) Starting from intermediate V.xi (1.14 g) and using procedure H followed by heating at 60° C. for 2 h in DCE, the title intermediate was obtained as a colourless solid (0.91 g, 88% yield).

(259) MS (ESI, m/z): 302.2 [M+H.sup.+].

V.xiii. (R)-4-aminomethyl-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(260) Starting from intermediate V.xi (0.91 g) and using procedure B, the title intermediate was obtained as a pale yellow solid (0.496 g, 82% yield).

(261) MS (ESI, m/z): 202.1 [M+H.sup.+].

Preparation W: (RS)-methanesulfonic acid 7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de][1,5]naphthyridin-4-ylmethyl ester

W.i. 3-(tert-butyl-dimethyl-silanyloxy)-2-(6-methoxy-[1,5]naphthyridin-4-yl)-propan-1-ol

(262) A solution of the intermediate V.i (1.10 g) in THF (55 mL) was treated at 0° C. with imidazole (351 mg) and a solution of TBDMSCl (707 mg) in THF (10 mL). After stirring at rt for 2 days, the reaction mixture was diluted with EA and extracted with water and brine. The org phase was dried over MgSO.sub.4 and purified by CC (Hept/EA 1.1 to 0:1), affording a colourless oil (570 mg; 35% yield).

(263) MS (ESI, m/z): 349.2 [M+H.sup.+].

W.ii. Methanesulfonic acid 3-(tert-butyl-dimethyl-silanyloxy)-2-(6-methoxy-[1,5]naphthyridin-4-yl)-propyl ester

(264) Starting from intermediate W.i (1.4 g) and MsCl (0.374 mL) and using procedure H, the title compound was obtained as a yellow oil (1.4 g, 81% yield).

(265) .sup.1H NMR (CDCl.sub.3) δ: 8.72 (d, J=4.4 Hz, 1H) 8.23 (d, J=9.1 Hz, 1H), 7.50 (d, J=4.7 Hz, 1H), 7.15 (d, J=9.1 Hz, 1H), 4.78 (m, 2H), 4.44 (m, 1H), 4.05 (m, 5H), 2.90 (s, 3H), 0.87 (m, 12H), −0.02 (d, J=8.5 Hz, 6H).

W.iii. 4-(tert-butyl-dimethyl-silanyloxymethyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(266) A solution of intermediate W.ii (1.4 g) in DCE (20 mL) was heated at 85° C. overnight. The reaction mixture was evaporated under reduced pressure. The residue was purified by CC (EA to EA/MeOH 9:1), affording a colourless oil (340 mg; 33% yield).

W.iv. 4-hydroxymethyl-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(267) Starting from intermediate W.iii (330 mg) and using procedure J, the title compound was obtained as a colourless solid (90 mg, 43% yield).

(268) MS (ESI, m/z): 203.2 [M+H.sup.+].

W.v. (RS)-methanesulfonic acid 7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de][1,5]naphthyridin-4-ylmethyl ester

(269) Starting from intermediate W.iv (90 mg) and using procedure H, the title compound was obtained as a yellow solid (90 mg, 72% yield).

(270) Analytical data identical to the (S)-enantiomer (intermediate V.v).

Preparation X: rac-1-amino-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

X.i. 2-azido-2-(2-methoxy-quinolin-8-yl)-ethanol

(271) A solution of 2-methoxy-8-(2-oxiranyl)-quinoline (900 mg; prepared according to WO 2006/046552) in dioxane/water (5:1; 60 mL) was reacted with NaN.sub.3 at 90° C. for 5 h. The solvents were removed under reduced pressure and the residue was purified by CC (Hex/EA 2:1 to 1:1), affording a yellow oil (480 mg; 44% yield).

(272) MS (ESI, m/z): 245.0 [M+H.sup.+].

X.ii. rac-2-amino-2-(2-methoxy-quinolin-8-yl)-ethanol

(273) Starting from intermediate X.i (470 mg) and using procedure F, the title compound was obtained as a yellow oil (450 mg; 100% yield).

(274) MS (ESI, m/z): 219.1 [M+H.sup.+].

X.iii. rac-[2-hydroxy-1-(2-methoxy-quinolin-8-yl)-ethyl]-carbamic acid tert-butyl ester

(275) Starting from intermediate X.ii (430 mg) and using procedure G, the title compound was obtained as a yellow oil (720 mg; quant.)

(276) MS (ESI, m/z): 319.1 [M+H.sup.+].

X.iv. rac-methanesulfonic acid 2-tert-butoxycarbonylamino-2-(2-methoxy-quinolin-8-yl)-ethyl ester

(277) Starting from intermediate X.iii (700 mg) and using procedure H, the title compound was obtained as a yellow oil (900 mg, quant.).

(278) MS (ESI, m/z): 397.0 [M+H.sup.+].

X.v. rac-(4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-carbamic acid tert-butyl ester

(279) A solution of intermediate X.iv (850 mg) in DCE (10 mL) was heated at 85° C. overnight. The solvent was evaporated under reduced pressure, affording a brown oil (780 mg; quant.) which was used without further purification in the next step.

(280) MS (ESI, m/z): 287.1 [M+H.sup.+].

X.vi. rac-1-amino-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(281) Starting from intermediate X.v (572 mg) and using procedure B, the title compound was obtained as a beige solid (230 mg; 62% yield).

(282) MS (ESI, m/z): 187.0 [M+H.sup.+].

Preparation Y: (S)-4-amino-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Y.i. (S)-2-azido-2-(6-methoxy-[1,5]naphthyridin-4-yl)-ethanol

(283) This compound was prepared in analogy to Preparation X, step X.i, but starting from 2-methoxy-8-[(2R)-2-oxiranyl]-1,5-naphthyridine (prepared according to WO 02/08224). The compound was purified by CC (Hept/EA 1:1 to 2:1 to 0:1), affording a yellow solid (3.9 g (87%; contaminated by its region isomer).

(284) MS (ESI, m/z): 246.3 [M+H.sup.+].

Y.ii. (S)-2-amino-2-(6-methoxy-[1,5]naphthyridin-4-yl)-ethanol

(285) Starting from intermediate Y.i (3.90 g) and using procedure F, the title compound was obtained as a yellow oil (2.80 g, 80% yield).

(286) MS (ESI, m/z): 220.0 [M+H.sup.+].

Y.iii. (S)-[2-hydroxy-1-(6-methoxy-[1,5]naphthyridin-4-yl)-ethyl]-carbamic acid tert-butyl ester

(287) Starting from intermediate Y.ii (2.90 g) and using procedure G, the title compound was obtained as a colourless foam (1.40 g, 33% yield).

(288) MS (ESI, m/z): 320.1 [M+H.sup.+].

Y.iv. ((S)-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de][1,5]naphthyridin-4-yl)-carbamic acid tert-butyl ester

(289) Starting from the intermediate Y.iii (1.40 g) and using procedure H followed by heating at 80° C. for 7 h, the title compound was obtained as a beige solid (570 mg, 45% yield).

(290) MS (ESI, m/z): 288.4 [M+H.sup.+].

Y.v. (S)-4-amino-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(291) Starting from intermediate Y.iv (570 mg) and using procedure B, the title compound was obtained as a beige solid (470 mg, quant.).

(292) .sup.1H NMR (CDCl.sub.3) δ: 8.43 (d, J=4.7 Hz, 1H), 7.79 (d, J=9.7 Hz, 1H), 7.43 (dd, J=4.7, 0.9 Hz, 1H), 6.74 (d, J=10.0 Hz, 1H), 4.91 (m, 1H), 4.52 (dd, J=13.2, 8.5 Hz, 1H), 4.02 (dd, J=13.5, 4.7 Hz, 1H).

Preparation Z: (S)-6-amino-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

Z.i. 2-methoxy-8-vinyl-quinoxaline

(293) A suspension of methyltriphenylphosphonium bromide (22.78 g) in THF (200 mL) was treated with tBuOK (7.15 g) and further stirred at rt for 1 h. The mixture was cooled to 0° C. and treated with a solution of 3-methoxy-5-quinoxalinecarboxaldehyde (10.0 g; prepared according to WO 2006/021448) in THF (100 mL). The mixture was further stirred at rt for 3 h, diluted with ether and washed with water and an aq. sat. NH.sub.4Cl solution. The org. phase was dried over MgSO.sub.4 and concentrated under reduced pressure. The residue was crystallized from ether and the crystals were filtered off. The mother liquor was purified by CC (Hex/EA 1:1), affording a light orange solid (8.70 g; 88% yield).

(294) .sup.1H NMR (CDCl.sub.3) δ: 8.48 (s, 1H), 7.92 (m, 2H), 7.78 (dd, J=17.9, 11.1 Hz, 1H), 7.54 (m, 1H), 6.03 (dd, J=17.9, 1.5 Hz, 1H), 5.48 (dd, J=11.4, 1.5 Hz, 1H), 4.12 (s, 3H).

Z.ii. (R)-1-(3-methoxy-quinoxalin-5-yl)-ethane-1,2-diol

(295) Starting from intermediate Z.i (8.70 g) and using procedure L with AD-mix β, the title compound was obtained as a beige solid (7.60 g, 74% yield) after crystallization from ether/EA.

(296) MS (ESI, m/z): 221.1 [M+H.sup.+].

Z.iii. (R)-2-(tert-butyl-dimethyl-silanyloxy)-1-(3-methoxy-quinoxalin-5-yl)-ethanol

(297) Starting from intermediate Z.ii (7.60 g) and using procedure M, the title compound was obtained as a yellow oil (8.80 g, 76% yield).

(298) MS (ESI, m/z): 335.0 [M+H.sup.+].

Z.iv. (S)-2-amino-2-(3-methoxy-quinoxalin-5-yl)-ethanol

(299) Starting from intermediate Z.iii (8.80 g) and using procedure N, the desired azide (20 g) was obtained, which was used without further purification in the next reaction. A solution of this azide (20 g, contaminated with PPh.sub.3O) in THF (228 mL) was then treated with PPh.sub.3 (7.50 g) and water (4.68 mL). The reaction mixture was further stirred at 50° C. for 2 days, and then extracted with 3M HCl. The aq. phase was basified with. aq. NaOH solution and extracted with EA. The org layer was dried over MgSO.sub.4 and evaporated under reduced pressure, affording a yellow oil (6.10 g; title compound contaminated with traces of PPh.sub.3O).

(300) MS (ESI, m/z): 220.0 [M+H.sup.+].

Z.v. [(S)-2-hydroxy-1-(3-methoxy-quinoxalin-5-yl)-ethyl]-carbamic acid tert-butyl ester

(301) Starting from intermediate Z.iv (6.00 g) and using procedure G, the title compound was obtained as a yellowish foam (5.90 g, 67% yield).

(302) MS (ESI, m/z): 320.1 [M+H.sup.+].

Z.vi. ((S)-3-oxo-5,6-dihydro-3H-pyrrolo[1,2,3-de]quinoxalin-6-yl)-carbamic acid tert-butyl ester

(303) A solution of intermediate Z.v (5.80 g) and TEA (3.0 mL) in DCE (45 mL) was treated dropwise at 0° C. with MsCl (1.55 mL). The reaction mixture was further refluxed overnight. The reaction mixture was diluted with DCM, washed with water and brine, dried over MgSO.sub.4 and evaporated under reduced pressure affording, after crystallization from ether/EA, a beige solid (3.50 g; 67% yield) consisting of an inseparable 2:1 mixture of the desired product and 4-(3-methoxy-quinoxalin-5-yl)-oxazolidin-2-one which was used as such in the next step.

(304) MS (ESI, m/z): 288.0 and 246.0 [M+H.sup.+].

Z.vii. (S)-6-amino-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

(305) Starting from intermediate Z.vi (3.50 g) and using procedure B, the title compound was obtained as a beige solid (780 mg, 34% yield). The side product from cyclisation was removed by acid/base extraction.

(306) MS (ESI, m/z): 188.1 [M+H.sup.+].

Preparation AA: (R)-6-amino-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

(307) The title compound was prepared in analogy to Preparation Z, using AD-mix α in the second step.

(308) The analytical data are identical to those of the compound of Preparation Z.

Preparation AB: rac-methanesulfonic acid 4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-ylmethyl ester

AB.i. 2-(2-methoxy-quinolin-8-yl)-malonic acid dimethyl ester

(309) A mixture of 8-bromo-2-methoxy-quinoline (4.76 g; prepared according to WO 2008/125594) and dimethylmalonate (36 mL) in was degassed by bubbling N.sub.2 through for 10 min and treated with CuBr (3.47 g) and NaOMe (2.6 g). The mixture was heated at 100° C. for 20 h and then partitioned between EA and water. The org. phase was washed with brine, dried over MgSO.sub.4 and the excess dimethylmalonate was removed by distillation. The residue was purified by CC (Hept/EA 4:1, 2:1), affording an oil (2.80 g; 48% yield).

(310) .sup.1H NMR (CDCl.sub.3) δ: 7.98 (d, J=8.8 Hz, 1H), 7.71 (dd, J=8.2, 1.5 Hz, 1H), 7.66 (m, 1H), 7.39 (m, 1H), 6.92 (d, J=8.8 Hz, 1H), 6.00 (s, 1H), 4.03 (s, 3H), 3.76 (s, 3H).

AB.ii. 2-(2-methoxy-quinolin-8-yl)-propane-1,3-diol

(311) Starting from intermediate AB.i (5.80 g) and using procedure A, the title compound was obtained as a light yellow oil (1.06 g, 23% yield).

(312) MS (ESI, m/z): 234.2 [M+H.sup.+].

AB.iii. rac-methanesulfonic acid 4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-ylmethyl ester

(313) Starting from intermediate AB.ii (840 mg) and using procedure H, but using 3 eq. of methanesulfonyl anhydride instead of MsCl and 4 eq. of Pyr as a base, the intermediate dimesylate was further stirred at 70° C. for 1 h. The reaction mixture was diluted with 2N HCl and extracted with DCM. The org. phase was dried over MgSO.sub.4 and evaporated under reduced pressure affording, after purification by CC (EE/MeOH 9:1), a beige foam (1.10 g; 76% yield).

(314) MS (ESI, m/z): 280.4 [M+H.sup.+].

Preparation AC: rac-6-aminomethyl-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

AC.i. (3-methoxy-quinoxalin-5-yl)-acetic acid methyl ester

(315) TBDMSCl (2.4 mL) was added dropwise to a solution of 3-methoxy-5-quinoxalineacetonitrile (1.08 g, prepared according to WO 2008/126024) in dry MeOH (20 mL). The solution was stirred at reflux overnight. TBDMSCl (2.4 mL) was added and the reaction mixture was further stirred for 8 h. TBDMSCl (2.4 mL) was added and the reaction mixture was further stirred at reflux overnight. The mixture was concentrated under reduced pressure and partitioned between EA and water. The org. layer was washed with 2M NaOH, water and brine, dried over MgSO.sub.4, concentrated under reduced pressure and purified by CC (Hept/EtOAc 1:1), affording a yellow oil (520 mg; 41% yield).

(316) MS (ESI, m/z): 233.3 [M+H.sup.+].

AC.ii. rac-3-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-2-(3-methoxy-quinoxalin-5-yl)-propionic acid methyl ester

(317) A solution of intermediate AC.i (2.03 g) in THF (19 mL) was added dropwise at −78° C. to a solution of LiHMDS (1M in THF; 10.5 mL) in THF (10 mL). The solution was further stirred at −78° C. stirred for 1 h and treated dropwise with a solution of N-(bromomethyl)phthalimide (2.6 g) in THF (19 mL). The reaction mixture was further stirred at −78° C. for 1 h and at rt overnight. The solution was quenched with 1N HCl (30 mL) and extracted with EA. The org. layer was washed with water and brine, dried over MgSO.sub.4, concentrated under reduced pressure and purified by CC (Hept/EA 1:1), affording, after crystallization from EA, a beige solid (2.28 g; 66% yield).

(318) MS (ESI, m/z): 392.3 [M+H.sup.+].

AC.iii. rac-3-amino-2-(3-methoxy-quinoxalin-5-yl)-propionic acid methyl ester

(319) Hydrazine monohydrate (1.42 mL) was added dropwise at rt to a suspension of intermediate AC.ii (2.28 g) in EtOH (38 mL). After stirring at rt for 2 h the solvent was evaporated under reduced pressure and the residue was taken up in EA and aq. citric acid (10%). The aq. layer was washed with NH.sub.4OH and extracted with DCM. The org. layer was dried over MgSO.sub.4 and evaporated under reduced pressure affording a yellow oil (1.16 g; 77% yield) which was further used without any further purification.

(320) MS (ESI, m/z): 262.3 [M+H.sup.+].

AC.iv. rac-3-tert-butoxycarbonylamino-2-(3-methoxy-quinoxalin-5-yl)-propionic acid methyl ester

(321) Starting from intermediate AC.iii (1.16 g) and using procedure G, the title compound was obtained as a colourless solid (1.34 g, 83% yield).

(322) MS (ESI, m/z): 362.0 [M+H.sup.+].

AC.v. rac-[3-hydroxy-2-(3-methoxy-1,2-dihydro-quinoxalin-5-yl)-propyl]-carbamic acid tert-butyl ester

(323) Starting from intermediate AC.iv (701 mg) and using procedure A, the compound was obtained as a colourless foam (554 mg, 85% yield).

(324) MS (ESI, m/z): 336.2 [M+H.sup.+].

AC.vi. rac-[3-hydroxy-2-(3-methoxy-quinoxalin-5-yl)-propyl]-carbamic acid tert-butyl ester

(325) A solution of intermediate AC.v (553 mg) in DCM (30 mL) was treated with MnO.sub.2 (1.35 g). The mixture was stirred at rt for 2 h, filtered and concentrated in vacuo to give the desired intermediate as a slightly orange foam (489 mg, 89% yield).

AC.vii. rac-(3-oxo-5,6-dihydro-3H-pyrrolo[1,2,3-de]quinoxalin-6-ylmethyl)-carbamic acid tert-butyl ester

(326) Starting from intermediate AC.vi (486 mg) and using procedure H, the title compound was obtained as a beige solid (393 mg, 89% yield).

(327) MS (ESI, m/z): 302.1 [M+H.sup.+].

AC.viii. rac-6-aminomethyl-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

(328) Starting from intermediate AC.viii (388 mg) and using procedure B, the title compound was obtained as a yellow solid (172 mg, 66% yield).

(329) MS (ESI, m/z): 202.3 [M+H.sup.+].

Preparation AD: (S)-6-amino-7-fluoro-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

AD.i. (R)-1-(6-fluoro-3-methoxy-quinoxalin-5-yl)-ethane-1,2-diol

(330) Starting from 7-fluoro-2-methoxy-8-(2-propen-1-yl)-quinoxaline (3.24 g; prepared according to WO 2008/003690) and using procedure L with AD-mix β, the title compound was obtained, after purification by CC (Hept/EA 1:1 then 0:1), as a beige solid (3.39 g, 90% yield).

(331) .sup.1H NMR (DMSO d6) δ: 8.57 (s, 1H), 7.96 (dd, J=9.1, 5.6 Hz, 1H), 7.48 (dd, J=10.3, 9.1 Hz, 1H), 5.64 (d, J=6.7 Hz, 1H), 5.26 (d, J=6.4 Hz, 1H), 4.75 (m, 1H), 4.05 (s, 3H), 3.88 (m, 1H), 3.73 (m, 1H).

AD.ii. (R)-2-(tert-butyl-dimethyl-silanyloxy)-1-(6-fluoro-3-methoxy-quinoxalin-5-yl)-ethanol

(332) Starting from intermediate AD.i (3.39 g) and using procedure M, the title compound was obtained as a colourless oil (4.83 g, 96% yield).

(333) .sup.1H NMR (CDCl.sub.3) δ: 8.47 (s, 1H), 7.95 (m, 1H), 7.35 (m, 1H), 5.5 (m, 1H), 4.09 (s, 3H), 4.03 (m, 2H), 0.76 (s, 9H), −0.12 (d, J=5.0 Hz, 6H).

AD.iii. (S)-[2-(tert-butyl-dimethyl-silanyloxy)-1-(6-fluoro-3-methoxy-quinoxalin-5-yl)-ethyl]-carbamic acid tert-butyl ester

(334) Starting from intermediate AD.ii (4.73 g) and using procedure N′, the title compound was obtained, after purification by CC (Hept/EA 4:1), as a colourless foam (3.48 g; 84% yield).

(335) .sup.1H NMR (CDCl.sub.3) δ: 8.45 (s, 1H), 7.93 (dd, J=9.1, 5.6 Hz, 1H), 7.30 (m, 1H), 6.60 (m, 1H), 5.85 (m, 1H), 4.12 (s, 4H), 3.94 (m, 2H), 1.43 (s, 9H), 0.75 (s, 9H), −0.08 (s, 3H), −0.12 (s, 3H).

AD.iv. (S)-[1-(6-fluoro-3-methoxy-quinoxalin-5-yl)-2-hydroxy-ethyl]-carbamic acid tert-butyl ester

(336) Starting from intermediate AD.iii (5.54 g) and using procedure J, the title compound was obtained as a colourless foam (3.48 g, 84% yield).

(337) .sup.1H NMR (CDCl.sub.3) δ: 8.45 (s, 1H), 7.95 (dd, J=9.4, 5.9 Hz, 1H), 7.34 (m, 1H), 6.60 (m, 1H), 5.85 (m, 1H), 4.11 (s, 3H), 3.92 (m, 2H), 1.42 (s, 9H).

AD.v. (S)-(7-fluoro-3-oxo-5,6-dihydro-3H-pyrrolo[1,2,3-de]quinoxalin-6-yl)-carbamic acid tert-butyl ester

(338) Starting from intermediate AD.iv (3.45 g) and using procedure H followed by heating at reflux for 12 h, a foam (2.64 g) was obtained which contained the desired product in a 1:1 mixture with (S)-4-(6-fluoro-3-methoxy-quinoxalin-5-yl)-oxazolidin-2-one. It was used as such in the next step.

AD.vi. (S)-6-amino-7-fluoro-5,6-dihydro-pyrrolo[1, 2,3-de]quinoxalin-3-one

(339) Starting from the mixture obtained at step AD.v (2.64 g, purity 50%) and using procedure B followed by acid/base extraction, the title compound was obtained as an orange solid (550 mg, 60% yield).

(340) .sup.1H NMR (DMSO d6) δ: 8.12 (s, 1H), 7.74 (dd, J=8.8, 4.4 Hz, 1H), 7.11 (m, 1H), 4.94 (dd, J=8.5, 3.8 Hz, 1H), 4.50 (dd, J=13.2, 8.5 Hz, 1H), 3.90 (dd, J=13.2, 3.8 Hz, 1H), 2.32 (br., 2H).

Preparation AE: rac-1-aminomethyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

AE.i. rac-1-azidomethyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(341) A solution of the compound of Preparation AB (1.00 g) in DMF (16 mL) was heated at 60° C. for 3 h in presence of NaN.sub.3 (2.80 g). The reaction mixture was diluted with water and extracted with EA. The org. layer was washed with water and brine, dried over MgSO.sub.4 and evaporated affording a yellow powder (800 mg; 99% yield).

(342) .sup.1H NMR (CDCl.sub.3) δ: 7.72 (d, J=9.4 Hz, 1H), 7.45 (m, 2H), 7.19 (m, 1H), 6.69 (d, J=9.4 Hz, 1H), 4.55 (dd, J=13.2, 9.4 Hz, 1H), 4.26 (dd, J=13.2, 4.7 Hz, 1H), 3.91 (m, 1H), 3.67 (m, 2H).

AE.ii. rac-1-aminomethyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(343) Starting from intermediate AE.i (800 mg) and using procedure F, the title compound was obtained as a yellow oil (310 mg, 44% yield).

(344) .sup.1H NMR (CDCl.sub.3) δ: 7.70 (d, J=9.4 Hz, 1H), 7.41 (m, 2H), 7.17 (t, J=7.6 Hz, 1H), 6.67 (d, J=9.4 Hz, 1H), 4.54 (dd, J=13.2, 9.7 Hz, 1H), 4.32 (dd, J=12.6, 4.7 Hz, 1H), 3.80 (m, 1H), 3.10 (d, J=6.2 Hz, 2H).

Preparation AF: 6-[(R)-5-(2-amino-ethyl)-2-oxo-oxazolidin-3-yl]-4H-benzo[1,4]thiazin-3-one

AF.i. 6-[(R)-5-(2-azido-ethyl)-2-oxo-oxazolidin-3-yl]-4H-benzo[1,4]thiazin-3-one

(345) A solution of the compound of Preparation J (2.5 g) and NaN.sub.3 (523 mg) in DMF (12 mL) was heated at 80° C. overnight. The reaction mixture was diluted with EA and extracted with water and brine. The org. layer was dried over MgSO.sub.4 and evaporated under reduced pressure. The residue was stirred in ether/MeOH, affording a beige solid (1.9 g; 89% yield).

(346) MS (ESI, m/z): 320.2 [M+H.sup.+].

AF.ii. 6-[(R)-5-(2-amino-ethyl)-2-oxo-oxazolidin-3-yl]-4H-benzo[1,4]thiazin-3-one

(347) Starting from intermediate AF.i (1.8 g) and using procedure F, the title compound was obtained as a colourless solid (1.40 g, 85% yield).

(348) MS (ESI, m/z): 294.4 [M+H.sup.+].

Preparation AG: methanesulfonic acid (S)-2-oxo-3-(4-propyl-phenyl)-oxazolidin-5-ylmethyl ester

AG.i. (S)-5-hydroxymethyl-3-(4-propyl-phenyl)-oxazolidin-2-one

(349) Starting from 4-propyl-aniline and following the procedure described for the preparation of intermediate R.i., the title compound was obtained as a yellow solid (4.3 g; 63% yield)

(350) MS (ESI, m/z): 235.9 [M+H.sup.+].

AG.ii. Methanesulfonic acid (S)-2-oxo-3-(4-propyl-phenyl)-oxazolidin-5-ylmethyl ester

(351) Starting from intermediate AG.i (4.25 g) and using procedure H (with however 1.5 eq. Ms.sub.2O instead of MsCl), the title compound was obtained as an off-white solid (4.30 g, 76% yield).

(352) MS (ESI, m/z): 314.1 [M+H.sup.+].

Preparation AH: methanesulfonic acid (S)-3-(4-butyl-phenyl)-2-oxo-oxazolidin-5-ylmethyl ester

AH.i. (S)-5-hydroxymethyl-3-(4-butyl-butyl)-oxazolidin-2-one

(353) Starting from 4-butyl-aniline and following the procedure described for the preparation of intermediate R.i, the title compound was obtained as a yellow solid (2.99 g; 58% yield).

(354) .sup.1H NMR (CDCl.sub.3) δ: 7.43 (d, J=8.8 Hz, 2H), 7.17 (d, J=8.8 Hz, 2H), 4.73 (m, 1H), 3.99 (m, 3H), 3.76 (m, 1H), 2.58 (m, 2H), 2.00 (br. s, 1H), 1.57 (m, 2H), 1.34 (m, 2H), 0.92 (t, J=7.0 Hz, 3H).

AH.ii. Methanesulfonic acid (S)-3-(4-butyl-phenyl)-2-oxo-oxazolidin-5-ylmethyl ester

(355) Starting from intermediate AH.i (2.90 g) and using procedure H (with however 1.5 eq. of Ms.sub.2O instead of MsCl), the title compound was obtained as an off-white solid (2.48 g, 65% yield).

(356) MS (ESI, m/z): 328.3 [M+H.sup.+].

Preparation AI: methanesulfonic acid 2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethyl ester

(357) The title compound was prepared in analogy to Preparation J, using however tert-butyl-dimethyl-[(S)-2-oxiranyl-ethoxy]-silane.

(358) The analytical data were identical with those of the compound of Preparation J.

Preparation AJ: methanesulfonic acid 2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethyl ester

AJ.i. (2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl)-carbamic acid tert-butyl ester

(359) A suspension of 2,3-dihydro-1,4-dioxino[2,3-c]pyridine-7-carboxylic acid (3.20 g; prepared according to WO 2007/016610) in tBuOH (100 mL) was treated with DPPA (4.60 mL) and TEA (3.0 mL) and heated at 80° C. overnight. The solvent was evaporated under reduced pressure and the residue as partitioned between water and EA. The org. layer was washed with brine, dried over MgSO.sub.4 and evaporated under reduced pressure. The residue was stirred in ether, affording a beige solid (2.90 g; 65% yield).

(360) .sup.1H NMR (CDCl.sub.3) δ: 7.84 (s, 1H), 7.49 (s, 1H), 4.31 (m, 2H), 4.23 (m, 2H), 1.52 (s, 11H).

AJ.ii. rac-5-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-3-(2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl)-oxazolidin-2-one

(361) A solution of intermediate AJ.i (3.30 g) and 2-[2-[[(tert-butyl)dimethylsilyl]oxy]ethyl]-oxirane (2.65 g; prepared according to J. Org. Chem. (2008), 73(3), 1093-1098) in DMF (42 mL) was cooled to 0° C. and treated with tBuOLi (18 mL; 2.2M in THF). The reaction mixture was allowed to reach rt and further stirred at 80° C. for 2 days. The reaction mixture was diluted with EA and washed with water and brine. The org. layer was dried over MgSO.sub.4 and purified by CC (Hex/EA1:1), affording a yellow oil (2.70 g; 54% yield).

(362) MS (ESI, m/z): 381.0 [M+H.sup.+].

AJ.iii. rac-3-(2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl)-5-(2-hydroxy-ethyl)-oxazolidin-2-one

(363) Starting from intermediate AJ.ii and using procedure J, the title compound was obtained as a yellow solid (1.10 g, 58% yield).

AJ.iv. Methanesulfonic acid 2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethyl ester

(364) Starting from intermediate AJ.iii and using procedure H, the title compound was obtained as a beige solid (1.30 g, 100% yield).

(365) MS (ESI, m/z): 345.2 [M+H.sup.+].

Preparation AK: rac-methanesulfonic acid 2-[3-(2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-6-yl)-2-oxo-oxazolidin-5-yl]-ethyl ester

AK.i. (2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-6-yl)-carbamic acid benzyl ester

(366) A solution of 2,3-dihydro-1,4-dioxino[2,3-b]pyridin-6-amine (commercial; 2.70 g) in acetone/water 1:1 (40 mL) was treated at 0° C. with 1M NaHCO.sub.3 (35 mL) and CbzCl (2.63 mL). The reaction mixture was stirred at rt for 3 h, the org. solvent was evaporated under reduced pressure and the residue was partitioned between water and ether/EA. The org layer was dried over MgSO.sub.4 and evaporated under reduced pressure, affording a beige solid (5.3 g; 100% yield).

(367) .sup.1H NMR (CDCl.sub.3) δ: 7.50 (d, J=8.5 Hz, 1H), 7.36 (m, 5H), 7.20 (d, J=8.8 Hz, 1H), 7.15 (br., 1H), 4.37 (m, 2H), 4.19 (m, 2H).

AK.ii. rac-5-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-3-(2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-6-yl)-oxazolidin-2-one

(368) Starting from intermediate AK.i and 2-[2-[[(tert-butyl)dimethylsilyl]oxy]ethyl]-oxirane, the compound was prepared in analogy to Preparation AJ, step AJ.ii. The product was purified by CC (Hex/EA 1:1), affording a brown oil (2.90 g; 73% yield).

(369) MS (ESI, m/z): 381.2 [M+H.sup.+].

AK.iii. rac-3-(2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-6-yl)-5-(2-hydroxy-ethyl)-oxazolidin-2-one

(370) Starting from intermediate AK.ii and using procedure J, the title compound was obtained as a yellow solid (1.10 g, 56% yield).

(371) MS (ESI, m/z): 266.8 [M+H.sup.+].

AK.iv. rac-methanesulfonic acid 2-[3-(2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-6-yl)-2-oxo-oxazolidin-5-yl]-ethyl ester

(372) Starting from intermediate AK.iii and using procedure H, the title compound was obtained as a beige solid (1.24 g, 96% yield).

(373) .sup.1H NMR (CDCl.sub.3) δ: 7.71 (d, J=8.8 Hz, 1H), 7.24 (m, 1H), 4.79 (m, 1H), 4.43 (m, 4H), 4.33 (m, 1H), 4.23 (m, 2H), 3.89 (dd, J=10.3, 6.7 Hz, 1H), 3.04 (s, 3H), 2.20 (m, 2H).

Preparation AL: methanesulfonic acid 2-[(R)-3-(4-ethoxy-phenyl)-2-oxo-oxazolidin-5-yl]-ethyl ester

AL.i. (R)-4-(tert-butyl-dimethyl-silanyloxy)-1-(4-ethoxy-phenylamino)-butan-2-ol

(374) A solution of 4-ethoxy-aniline (commercial; 3.2 mL) in EtOH/water (9:1; 150 mL) was reacted with (2R)-2-[2-[[(tert-butyl)dimethylsilyl]oxy]ethyl]-oxirane (prepared according to WO 2007/144423) and further heated at 80° C. overnight. The solvents were removed under reduced pressure and the residue was purified by CC (EA/Hept 1:1), affording a brown oil (5.22 g; 62% yield).

(375) MS (ESI, m/z): 340.2 [M+H.sup.+].

AL.ii. (R)-5-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-3-(4-ethoxy-phenyl)-oxazolidin-2-one

(376) Starting from intermediate AL.i and using procedure I, the title compound was obtained as an off-white solid (4.30 g, 76% yield).

(377) MS (ESI, m/z): 366.1 [M+H.sup.+].

AL.iii. (R)-3-(4-ethoxy-phenyl)-5-(2-hydroxy-ethyl)-oxazolidin-2-one

(378) Starting from intermediate AL.ii and using procedure J, the title compound was obtained as an off-white solid (1.53 g, 52% yield).

(379) MS (ESI, m/z): 251.9 [M+H.sup.+].

AL.iv. Methanesulfonic acid 2-[(R)-3-(4-ethoxy-phenyl)-2-oxo-oxazolidin-5-yl]-ethyl ester

(380) Starting from intermediate AL.iii and using procedure H, the title compound was obtained as an off-white solid (1.89 g, 96% yield).

(381) MS (ESI, m/z): 330.0 [M+H.sup.+].

Preparation AM: methanesulfonic acid 2-[(R)-2-oxo-3-(4-propyl-phenyl)-oxazolidin-5-yl]-ethyl ester

AM.i. (R)-4-(tert-butyl-dimethyl-silanyloxy)-1-(4-propyl-phenylamino)-butan-2-ol

(382) Starting from 4-propyl-aniline, the title compound was prepared in analogy to Preparation AL, step AL.i. A brown oil (6.99 g; 84% yield) was obtained.

(383) MS (ESI, m/z): 338.2 [M+H.sup.+].

AM.ii. (R)-5-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-3-(4-propyl-phenyl)-oxazolidin-2-one

(384) Starting from intermediate AM.i and using procedure I, the title compound was obtained as a brown oil (4.50 g, 60% yield).

(385) MS (ESI, m/z): 364.1 [M+H.sup.+].

AM.iii. (R)-5-(2-hydroxy-ethyl)-3-(4-propyl-phenyl)-oxazolidin-2-one

(386) Starting from intermediate AM.ii and using procedure J, the title compound was obtained as a yellowish solid (1.76 g, 57% yield).

(387) MS (ESI, m/z): 249.9 [M+H.sup.+].

AM.iv. Methanesulfonic acid 2-[(R)-2-oxo-3-(4-propyl-phenyl)-oxazolidin-5-yl]-ethyl ester

(388) Starting from intermediate AM.iii and using procedure H, the title compound was obtained as an off-white solid (2.13 g, 93% yield).

(389) MS (ESI, m/z): 328.4 [M+H.sup.+].

Preparation AN: methanesulfonic acid 2-[(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-yl]-ethyl ester

AN.i. (R)-4-(tert-butyl-dimethyl-silanyloxy)-1-(2,3-dihydro-benzo[1,4]dioxin-6-ylamino)-butan-2-ol

(390) Starting from 2,3-dihydro-1,4-benzodioxin-6-amine (commercial), the title compound was prepared in analogy to Preparation AL, step AL.i. A brown oil (4.50 g; 51% yield) was obtained.

(391) MS (ESI, m/z): 354.3 [M+H.sup.+].

AN.ii. (R)-5-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-oxazolidin-2-one

(392) Starting from intermediate AN.i and using procedure I, the title compound was obtained as a yellow solid (3.42 g, 71% yield).

(393) MS (ESI, m/z): 380.2 [M+H.sup.+].

AN.iii. (R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-5-(2-hydroxy-ethyl)-oxazolidin-2-one

(394) Starting from intermediate AN.ii and using procedure J, the title compound was obtained as an off-white solid (1.72 g, 72% yield).

(395) .sup.1H NMR (CDCl.sub.3) δ: 7.06 (d, J=2.6 Hz, 1H), 6.97 (dd, J=8.8, 2.6 Hz, 1H), 6.84 (m, 1H), 4.81 (m, 1H), 4.24 (m, 4H), 4.06 (t, J=8.8 Hz, 1H), 3.88 (m, 2H), 3.69 (dd, J=8.8, 7.3 Hz, 1H), 2.03 (m, 2H), 1.82 (br. s, 1H).

AN.iv. Methanesulfonic acid 2-[(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-yl]-ethyl ester

(396) Starting from intermediate AN.iii and using procedure H, the title compound was obtained as an off-white solid (2.03 g, 92% yield).

(397) MS (ESI, m/z): 344.2 [M+H.sup.+].

Preparation AO: rac-methanesulfonic acid 2-{3-[4-(4-methoxy-benzyl)-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl]-2-oxo-oxazolidin-5-yl}-ethyl ester

AO.i. 6-bromo-4-(4-methoxy-benzyl)-4H-pyrido[3,2-b][1,4]oxazin-3-one

(398) A suspension of 6-bromo-2H-pyrido[3,2-b]-1,4-oxazin-3(4H)-one (2.0 g; prepared according to WO 01/30782) in DMF (40 mL) was treated with 4-methoxybenzyl chloride (1.18 mL) and Cs.sub.2CO.sub.3 (8.5 g) and stirred at rt for 2 h. The solvent was evaporated under reduced pressure and the residue was partitioned between EA and water. The org. layer was washed with brine, dried over MgSO.sub.4 and evaporated under reduced pressure. The residue was triturated with Hept, affording a beige solid (2.8 g; 92% yield).

(399) .sup.1H NMR (CDCl.sub.3) δ: 7.49 (d, J=8.8 Hz, 2H), 7.05 (s, 2H), 6.83 (d, J=8.8 Hz, 2H), 6.83 (d, J=8.8 Hz, 2H), 6.83 (d, J=8.8 Hz, 2H), 4.67 (s, 2H), 3.77 (s, 3H).

AO.ii. rac-1-azido-4-(tert-butyl-dimethyl-silanyloxy)-butan-2-ol

(400) A solution of 2-[2-[[(tert-butyl)dimethylsilyl]oxy]ethyl]-oxirane (5.0 g; prepared according to WO 2007/144423) in MeOH (150 mL) was reacted with NaN.sub.3 (3.95 g) and NH.sub.4Cl (2.37 g). The reaction mixture was further stirred at 80° C. overnight. The solvent was evaporated under reduced pressure and the residue was partitioned between EA and water. The org. layer was washed with brine, dried over Na.sub.2SO.sub.4 and evaporated under reduced pressure, affording a yellow oil (4.9 g; 81% yield).

(401) .sup.1H NMR (CDCl.sub.3) δ: 4.01 (m, 1H), 3.87 (m, 2H), 3.30 (m, 2H), 1.72 (m, 2H), 0.90 (m, 9H), 0.06 (m, 6H).

AO.iii. rac-1-amino-4-(tert-butyl-dimethyl-silanyloxy)-butan-2-ol

(402) A solution of intermediate AO.ii (4.85 g) in THF (100 mL) was hydrogenated for 3 h over 10% Pd/C (1.0 g). The catalyst was filtered off and the filtrate was evaporated under reduced pressure, affording a yellow oil (4.1 g; 94.5% yield).

(403) MS (ESI, m/z): 219.8 [M+H.sup.+].

AO.iv. rac-5-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-oxazolidin-2-one

(404) Starting from intermediate AO.iii (4.0 g) and using procedure I, the title compound was obtained as a light yellow oil (3.3 g; 74% yield).

(405) .sup.1H NMR (CDCl.sub.3) δ: 5.22 (br., 1H), 4.80 (m, 1H), 3.74 (m, 3H), 3.33 (m, 1H), 1.93 (m, 2H), 0.89 (m, 9H), 0.07 (m, 6H).

AO.v. rac-6-{5-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-2-oxo-oxazolidin-3-yl}-4-(4-methoxy-benzyl)-4H-pyrido[3,2-b][1,4]oxazin-3-one

(406) Intermediates AO.iv (1.97 g) and AO.i (2.8 g), CuI (305 mg) and K.sub.2CO.sub.3 (2.2 g) were placed in a round bottom flask which was then flushed with argon. Trans-1,2-diaminocyclohexane (1.2 mL) and dioxane (60 mL) were added to the mixture and the reaction flask was again flushed with argon. The reaction mixture was stirred at 100° C. for 2 days and partitioned between EA and water. The org. layer was washed with brine, dried over MgSO.sub.4 and evaporated under reduced pressure. The residue was purified by CC (DCM/MeOH 19:1), affording, after crystallisation from Hept, a colourless solid (1.7 g; 41% yield).

(407) .sup.1H NMR (CDCl.sub.3) δ: 7.81 (d, J=8.8 Hz, 1H), 7.28 (m, 3H), 6.81 (m, 2H), 5.20 (s, 2H), 4.82 (m, 1H), 4.28 (m, 1H), 3.85 (m, 3H), 3.77 (s, 3H), 2.00 (m, 2H), 0.89 (s, 9H), 0.07 (s, 6H).

AO.vi. rac-6-[5-(2-hydroxy-ethyl)-2-oxo-oxazolidin-3-yl]-4-(4-methoxy-benzyl)-4H-pyrido[3,2-b][1,4]oxazin-3-one

(408) Starting from intermediate AO.v (1.7 g) and using procedure J, the title compound was obtained, after purification by CC (EA then EA/MeOH 9:1), as a yellow oil (1.4 g; 100% yield).

(409) MS (ESI, m/z): 400.0 [M+H.sup.+].

AO.vii. rac-methanesulfonic acid 2-{3-[4-(4-methoxy-benzyl)-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl]-2-oxo-oxazolidin-5-yl}-ethyl ester

(410) Starting from intermediate AO.vi (1.32 g) and using procedure H, the title compound was obtained as a colourless foam (1.3 g; 82.5% yield)

(411) MS (ESI, m/z): 477.8 [M+H.sup.+].

Preparation AP: 6-[(S)-5-(2-amino-ethyl)-2-oxo-oxazolidin-3-yl]-4H-benzo[1,4]thiazin-3-one

AP.i. 6-[(S)-5-(2-azido-ethyl)-2-oxo-oxazolidin-3-yl]-4H-benzo[1,4]thiazin-3-one

(412) A solution of intermediate L (1.90 g) in DMF (8 mL) was treated with NaN.sub.3 (400 mg) and stirred at 80° C. overnight. The reaction mixture was diluted with water and extracted with EA. The org. layer was washed with water and brine, dried over MgSO.sub.4 and evaporated under reduced pressure. The residue was stirred in ether/MeOH, affording a beige solid (1.30 g; 80% yield).

(413) MS (ESI, m/z): 320.3 [M+H.sup.+].

AP.ii. 6-[(S)-5-(2-amino-ethyl)-2-oxo-oxazolidin-3-yl]-4H-benzo[1,4]thiazin-3-one

(414) Starting from intermediate AP.i and using procedure F, the title compound was obtained as a beige solid (0.90 g, 82% yield).

(415) MS (ESI, m/z): 294.4 [M+H.sup.+].

Preparation AQ: methanesulfonic acid 2-[(S)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-yl]-ethyl ester

(416) Starting from (2S)-2-[2-[[(tert-butyl)dimethylsilyl]oxy]ethyl]-oxirane, the title compound was prepared in analogy to Preparation AN.

(417) The analytical data were identical with those of the compound of Preparation AN.

Preparation AR: 3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propionaldehyde

AR.i. (R)-1-azido-5-(tert-butyl-dimethyl-silanyloxy)-pentan-2-ol

(418) Starting from (R)-2-[2-[[(tert-butyl)dimethylsilyl]oxy]propyl]-oxirane (5.0 g; prepared according to Organic Letters (2005), 7(18), 3997-4000) and NaN.sub.3, the title compound was prepared in analogy to Preparation AO, step AO.ii. It was obtained as an oil (5.17 g; 86% yield).

(419) .sup.1H NMR (CDCl.sub.3) δ: 3.79 (m, 1H), 3.68 (m, 2H), 3.29 (m, 2H), 1.66 (m, 4H), 0.90 (m, 9H), 0.07 (m, 6H).

AR.ii. (R)-5-[2-(tert-butyl-dimethyl-silanyloxy)-propyl]-oxazolidin-2-one

(420) The title compound was prepared in analogy to Preparation AO, steps AO.iii and AO.iv by hydrogenation of intermediate AR.ii using procedure F and reaction with CDI using procedure I. It was obtained as a colourless solid (3.48 g; 67% yield).

(421) .sup.1H NMR (CDCl.sub.3) δ: 5.22 (br., 1H), 4.68 (m, 1H), 3.66 (m, 3H), 3.25 (t, J=7.6 Hz, 1H), 1.72 (m, 4H), 0.89 (m, 9H), 0.05 (m, 6H).

AR.iii. (R)-6-{5-[2-(tert-butyl-dimethyl-silanyloxy)-propyl]-2-oxo-oxazolidin-3-yl}-4-(4-methoxy-benzyl)-4H-pyrido[3,2-b][1,4]oxazin-3-one

(422) Starting from intermediates AO.i (1.97 g) and AR.ii, the title compound was prepared in analogy to Preparation AO, step AO.v. It was obtained as a colourless foam (4.43 g; 70% yield).

(423) .sup.1H NMR (CDCl.sub.3) δ: 7.80 (d, J=8.5 Hz, 1H), 7.28 (m, 3H), 6.81 (d, J=8.8 Hz, 2H), 5.20 (s, 2H), 4.67 (m, 3H), 4.22 (dd, J=10.0, 8.5 Hz, 1H), 3.77 (s, 3H), 3.70 (m, 2H), 1.78 (m, 4H), 0.90 (m, 9H), 0.06 (s, 6H).

AR.iv. (R)-6-[5-(2-hydroxy-propyl)-2-oxo-oxazolidin-3-yl]-4-(4-methoxy-benzyl)-4H-pyrido[3,2-b][1,4]oxazin-3-one

(424) The title compound was prepared in analogy to Preparation AO, step AO.vi, starting from intermediate AR.iii. It was obtained as a colourless solid (640 mg; 38% yield).

(425) .sup.1H NMR (DMSO d6) δ: 11.16 (s, 1H), 7.57 (m, 1H), 7.40 (d, J=8.8 Hz, 1H), 4.68 (s, 1H), 4.59 (s, 2H), 4.47 (t, J=5.0 Hz, 1H), 4.19 (m, 1H), 3.69 (dd, J=10.0, 7.0 Hz, 1H), 3.43 (q, J=6.2 Hz, 2H), 1.73 (m, 2H), 1.51 (dd, J=9.7, 6.7 Hz, 2H).

AR.v. 3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propionaldehyde

(426) A solution of SO.sub.3.Pyr complex (900 mg) in DMSO (3 mL) was added dropwise at rt over 10 min to a suspension of intermediate AR.iv (830 mg) and DIPEA (1.45 mL) in DCM/DMSO (1:1; 5 mL). The mixture was further stirred at rt for 1 h, diluted with water and extracted with DCM. The org. layer was successively washed with water and brine, dried over MgSO.sub.4, concentrated under reduced pressure and crystallized from ether/EA, affording a colourless solid (618 mg; 75% yield).

(427) .sup.1H NMR (DMSO d6) δ: 11.17 (s, 1H), 9.68 (s, 1H), 7.57 (m, 1H), 7.40 (d, J=8.8 Hz, 1H), 4.66 (m, 1H), 4.59 (s, 2H), 4.20 (m, 1H), 3.70 (dd, J=10.0, 7.0 Hz, 1H), 2.59 (m, 2H), 1.98 (m, 2H).

Preparation AS: (S)-1-amino-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

AS.i. 2-methoxy-8-vinyl-quinoline

(428) (PPh.sub.3).sub.4Pd (578 mg) was added at rt to a solution of vinylboronic anhydride pyridine complex (1.2 g) in DME (80 mL). The solution was degassed by bubbling N.sub.2 through for 20 min. K.sub.2CO.sub.3 (1.38 g), water (24 mL) and trifluoro-methanesulfonic acid 2-methoxy-quinolin-8-yl ester (3.07 g) were added. The mixture was refluxed overnight, cooled to rt and partitioned between water and ether. The aq. phase was washed with ether and the combined org. phases were washed with water and brine, dried over MgSO.sub.4, concentrated under reduced pressure and purified by CC (Hept/EA 4:1), affording a yellow liquid (1.18 g; 64% yield).

(429) .sup.1H NMR (CDCl.sub.3) δ: 7.97 (d, J=8.8 Hz, 1H), 7.88 (m, 2H), 7.64 (dd, J=7.9, 1.5 Hz, 1H), 7.36 (t, J=7.6 Hz, 1H), 6.91 (d, J=8.8 Hz, 1H), 6.02 (dd, J=17.9, 1.8 Hz, 1H), 5.45 (dd, J=11.1, 1.8 Hz, 1H), 4.10 (s, 3H).

AS.ii. (R)-1-(2-methoxy-quinolin-8-yl)-ethane-1,2-diol

(430) Starting from intermediate AS.i and AD-mix β and using procedure L, the title compound was obtained as a beige solid (3.22 g, quant).

(431) MS (ESI, m/z): 279.3 [M+H.sup.+].

AS.iii. (R)-2-(tert-butyl-dimethyl-silanyloxy)-1-(2-methoxy-quinolin-8-yl)-ethanol

(432) Starting from intermediate AS.ii and using procedure M, the title compound was obtained as a yellow oil (4.16 g, quant.).

(433) MS (ESI, m/z): 334.0 [M+H.sup.+].

AS.iv. [(S)-2-(tert-butyl-dimethyl-silanyloxy)-1-(2-methoxy-quinolin-8-yl)-ethyl]-carbamic acid tert-butyl ester

(434) Starting from intermediate AS.iii (4.70 g), the title compound was prepared in analogy to Preparation Z, steps Z.iv (Mitsunobu reaction followed by azide reduction) and Z.v. (Boc protection using procedure G). It was obtained as a slightly yellow oil (8.4 g; quant.; contaminated by Boc.sub.2O).

(435) MS (ESI, m/z): 359.3 [M+H.sup.+].

AS.v. [(S)-2-hydroxy-1-(2-methoxy-quinolin-8-yl)-ethyl]-carbamic acid tert-butyl ester

(436) Starting from intermediate AS.iv (6.48 g) and using procedure J, the title compound was obtained as a colourless foam (2.99 g; 63% yield).

(437) MS (ESI, m/z): 319.0 [M+H.sup.+].

AS.vi. ((S)-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-carbamic acid tert-butyl ester

(438) Starting from intermediate AS.v (3.34 g) and using procedure H (but heating the reaction mixture at 50° C.), the title compound was obtained as a colourless solid (2.64 g; 88% yield).

(439) MS (ESI, m/z): 287.1 [M+H.sup.+].

AS.vii. (S)-1-amino-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(440) Starting from intermediate AS.vi (2.63 g) and using procedure B, the title compound was obtained as a colourless solid (1.58 g; 93% yield).

(441) MS (ESI, m/z): 187.1 [M+H.sup.+].

Preparation AT: (S)-4-aminomethyl-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

AT.i. Acetic acid (S)-3-azido-2-(6-methoxy-[1,5]naphthyridin-4-yl)-propyl ester

(442) Starting from intermediate V.ii (1.65 g) and using the same procedure as for the preparation of intermediate Z.iv, the title compound was obtained as a colourless oil (1.63 g; 90% yield).

(443) MS (ESI, m/z): 302.0 [M+H.sup.+].

AT.ii. Acetic acid (S)-3-tert-butoxycarbonylamino-2-(6-methoxy-[1,5]naphthyridin-4-yl)-propyl ester

(444) Starting from intermediate AT.i (1.63 g) and using successively procedures F and G, the title compound was obtained as pale yellow oil (2.04 g; 100% yield).

(445) MS (ESI, m/z): 376.2 [M+H.sup.+].

AT.iii. [(S)-3-hydroxy-2-(6-methoxy-[1,5]naphthyridin-4-yl)-propyl]-carbamic acid tert-butyl ester

(446) A suspension of intermediate AT.ii (2.05 g) and K.sub.2CO.sub.3 (3.02 g) in MeOH (72 mL) was stirred at rt for 30 min. The solvent was removed under reduced pressure and the residue was taken up in DCM/water. The org. layer was washed with brine, dried over MgSO.sub.4, concentrated and purified by CC (DCM/MeOH/NH.sub.4OH 1000:50:4), affording a colourless foam (1.28 g; 70% yield).

(447) MS (ESI, m/z): 334.2 [M+H.sup.+].

AT.iv. ((S)-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de][1,5]naphthyridin-4-ylmethyl)-carbamic acid tert-butyl ester

(448) Starting from intermediate AT.iii (1.28 g) and using procedure H for the formation of the mesylate, followed by heating of the reaction mixture for 2 h at 60° C. to complete the cyclisation, the title compound was obtained as a colourless foam (985 mg; 85% yield).

(449) MS (ESI, m/z): 302.2 [M+H.sup.+].

AT.v. (S)-4-aminomethyl-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(450) Starting from intermediate AT.iv (980 mg) and using procedure B, the title compound was obtained as pale yellow solid (522 mg; 80% yield).

(451) MS (ESI, m/z): 202.2 [M+H.sup.+].

Preparation AU: 3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propionaldehyde

(452) Starting from (S)-tert-butyl-dimethyl-(3-oxiranyl-propoxy)-silane (prepared according to Org. Lett. (2005), 7(19), 4083-4086), the title compound (obtained as a pink solid) was prepared in analogy to Preparation U in 4 steps (epoxide opening: 50% yield; oxazolidinone formation: 100% yield; alcohol deprotection: 71% yield; aldehyde formation: 91% yield).

(453) The analytical data were identical with those of the compound of Preparation U.

Preparation AV: 3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propionaldehyde

(454) Starting from (S)-tert-butyl-dimethyl-(3-oxiranyl-propoxy)-silane (prepared according to Org. Lett. (2005), 7(19), 4083-4086), the title compound (obtained as a beige solid) was prepared in analogy to Preparation T in 4 steps (epoxide opening: 45% yield, oxazolidinone formation: 100% yield, alcohol deprotection: 65% yield, aldehyde formation: 87% yield).

(455) The analytical data were identical with those of the compound of Preparation T.

Preparation AW: methanesulfonic acid 3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl ester

AW.i. 6-[(S)-5-(tert-butyl-dimethyl-silanyloxy)-2-hydroxy-pentylamino]-4H-benzo[1,4]thiazin-3-one

(456) A mixture of (S)-tert-butyl-dimethyl-(3-oxiranyl-propoxy)-silane (28.3 g, prepared according to Org. Lett. (2005), 7, 3997) and 6-amino-4H-benzo[1,4]thiazin-3-one (23.6 g) in MeCN (390 mL) was treated with LiClO.sub.4 (41.8 g) and heated at 60° C. for 4 h. The volatiles were removed under reduced pressure and the residue partitioned between EA and brine. The org. phase was dried over MgSO.sub.4 and concentrated. The residue was purified by CC (Hept/EA 1:1, EA) to give the desired intermediate as a yellowish foam (8.4 g; 16% yield).

(457) MS (ESI, m/z): 397.1 [M+H.sup.+].

AW.ii. 6-{(S)-5-[3-(tert-butyl-dimethyl-silanyloxy)-propyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]thiazin-3-one

(458) A solution of intermediate AW.i (8.0 g) in THF (500 mL) was treated with CDI (4.9 g) and heated at 50° C. overnight. The mixture was cooled to rt, diluted with EA and washed with water and brine, dried over MgSO.sub.4 and concentrated. The product was crystallized from Hept/EA to give the desired oxazolidinone as a beige solid (4.5 g; 53% yield).

(459) MS (ESI, m/z): 423.4 [M+H.sup.+].

AW.iii. 6-[(S)-5-(3-hydroxy-propyl)-2-oxo-oxazolidin-3-yl]-4H-benzo[1,4]thiazin-3-one

(460) A suspension of intermediate AW.ii (4.5 g) in THF (42 mL) was treated with 1M TBAF solution in THF (1 eq.). The brown solution was stirred at rt for 4 h, diluted with EA and washed with water and brine, dried over MgSO.sub.4 and concentrated. The residue was purified by CC (EA then EA/MeOH 9:1) to give the desired alcohol as a yellowish foam (3.6 g; 100% yield).

(461) MS (ESI, m/z): 309.3 [M+H.sup.+].

AW.iv. Methanesulfonic acid 3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl ester

(462) A suspension of intermediate AW.iii (3.0 g) in DCM was treated with TEA (2.8 mL) and dropwise with MsCl (1.37 g). The mixture was stirred at rt for 2 h, diluted with DCM, washed with water, dried over MgSO.sub.4 and concentrated. The residue was crystallized from ether/EA to give the desired mesylate as a beige solid (3.6 g; 93% yield).

(463) MS (ESI, m/z): 387.2 [M+H.sup.+].

Preparation AX: rac-4-amino-3-fluoro-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

AX.i. 7-fluoro-2-methoxy-8-vinyl-[1,5]naphthyridine

(464) To a solution of 8-bromo-7-fluoro-2-methoxy-1,5-naphthyridine (5.0 g; commercial) in 1,2-DME (150 mL) was added tetrakis-(PPh.sub.3)Pd (1.1 g) and the mixture was purged with N.sub.2 for 20 min. K.sub.2CO.sub.3 (2.69 g), water (50 mL) and vinylboronic anhydride pyridine complex (2.34 g) were added. The mixture was stirred at reflux for 3 h. After cooling to rt, water was added and the mixture was extracted with EA. The combined org. phases were washed with brine, dried over MgSO.sub.4, concentrated and purified by CC (EA/Hept 1:1), affording the title intermediate as a brown oil (3.12 g, 79% yield).

(465) MS (ESI, m/z): 205.0 [M+H.sup.+].

AX.ii. (R)-1-(3-fluoro-6-methoxy-[1,5]naphthyridin-4-yl)-ethane-1,2-diol

(466) Starting from intermediate AX.i (3.12 g) and using procedure L with AD-mix β, the title compound was obtained as an off-white solid (4 g, quant.).

(467) MS (ESI, m/z): 239.0 [M+H.sup.+].

AX.iii. (R)-2-(tert-butyl-dimethyl-silanyloxy)-1-(3-fluoro-6-methoxy-[1,5]naphthyridin-4-yl)-ethanol

(468) To a solution of intermediate AX.ii (3.96 g) in DCM (160 mL) were added imidazole (1.05 eq.), TBDMSCl (1.05 eq.) and DMAP (0.1 eq.). The mixture was stirred at rt for 1 h. Water was added and the mixture was extracted with DCM. The org. layer was dried over MgSO.sub.4 and concentrated to afford the title intermediate as a yellow oil (4.52 g, 77%).

(469) MS (ESI, m/z): 353.2 [M+H.sup.+].

AX.iv. [(S)-2-(tert-butyl-dimethyl-silanyloxy)-1-(3-fluoro-6-methoxy-[1,5]naphthyridin-4-yl)-ethyl]-carbamic acid tert-butyl ester

(470) Starting from intermediate AX.iii (4.52 g) and using procedure N′, the title intermediate was obtained as a light yellow oil (6.76 g, quant.).

(471) MS (ESI, m/z): 452.2 [M+H.sup.+].

AX.v. [(S)-1-(3-fluoro-6-methoxy-[1,5]naphthyridin-4-yl)-2-hydroxy-ethyl]-carbamic acid tert-butyl ester

(472) Starting from intermediate AX.iv (6.76 g) and using procedure J, the title intermediate was obtained as a yellow oil (3.96 g, 78% yield).

(473) MS (ESI, m/z): 338.2 [M+H.sup.+].

AX.vi. ((S)-3-fluoro-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de][1,5]naphthyridin-4-yl)-carbamic acid tert-butyl ester

(474) Starting from intermediate AX.v (3.46 g) and using procedure H followed by heating at 80° C. for 18 h in DCE, the title intermediate was obtained as a yellow oil (0.90 g, 28% yield).

(475) MS (ESI, m/z): 306.2 [M+H.sup.+].

AX.vii. rac-4-amino-3-fluoro-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(476) Starting from intermediate AX.vi (0.875 g) and using procedure B, the title intermediate was obtained as a pale yellow solid (0.42 g, 71% yield). An analysis of the ee-value indicated that the product was present as a racemate. Since no ee-determinations in previous steps have been made, a racemisation at an earlier stage in the synthetic sequence cannot be excluded.

(477) MS (ESI, m/z): 206.1 [M+H.sup.+].

Preparation AY: methanesulfonic acid 2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethyl ester

(478) Starting from tert-butyl-dimethyl-[(S)-2-oxiranyl-ethoxy]-silane, the title compound was prepared in analogy to Preparation I.

(479) The analytical data were identical with those of the compound of Preparation I.

Preparation AZ: (R)-6-amino-7-fluoro-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

(480) The title compound was prepared as described in Preparation AD, using however AD-mix α in the first step.

(481) The analytical data were identical with those of the compound of Preparation AD.

Preparation BA: 6-{5-[(1RS)-1-(tert-butyl-dimethyl-silanyloxy)-3-hydroxy-propyl]-((5RS)-2-oxo-oxazolidin-3-yl)}-4H-benzo[1,4]thiazin-3-one

BA.i. (3RS)-3-(tert-butyl-dimethyl-silanyloxy)-3-((2RS)-oxiran-2-yl)-propionic acid tert-butyl ester

(482) A solution of 3-[[(tert-butyl-dimethylsilyl]oxy]-4-pentenoic acid tert-butyl ester (3.60 g; prepared according to J. Org. Chem. (1994), 59, 4760-4764) in DCM (100 mL) was reacted with MCPBA (3.96 g) for 2 days. The reaction mixture was partitioned between DCM and an aq. solution containing Na.sub.2S.sub.2O.sub.3 (10%) and NaHCO.sub.3 (sat.). The org. phase was separated, dried over MgSO.sub.4, evaporated under reduced pressure and purified by CC (Hept/EA 9:1 to 4:1), affording a colourless liquid (2.55 g; 67% yield; 3:2 mixture of diastereomers).

(483) .sup.1H NMR (CDCl.sub.3) δ: 4.02 (m, 1H, diast. B), 3.76 (d, J=6.4 Hz, 1H, diast. A), 3.02 (m, 1H, diast. A), 2.99 (m, 1H, diast. B), 2.8-2.4 (m, 4H, diast. A and B), 1.45 (s, 9H, diast. A and B), 0.88 (m, 9H, diast. A and B), 0.10 (m, 6H, diast. A and B).

BA.ii. (3RS)-3-(tert-butyl-dimethyl-silanyloxy)-(4RS)-4-hydroxy-5-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-ylamino)-pentanoic acid tert-butyl ester

(484) A solution of intermediate BA.i (6.05 g) and 6-amino-4H-benzo[1,4]thiazin-3-one (3.60 g) in EtOH/water (9:1; 100 mL) was refluxed for 30 h. The org. solvent was removed under reduced pressure and the residue was taken up in EA (20 mL) and filtered. The filtrate was concentrated under reduced pressure and purified by CC (Hept/EA 1:1 to 1:2), affording after trituration in EA/ether, a colourless solid (3.26 g; 34% yield).

(485) MS (ESI, m/z): 483.2 [M+H.sup.+].

BA.iii. (3RS)-3-(tert-butyl-dimethyl-silanyloxy)-3-[((5RS)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1, 4]thiazin-6-yl))-oxazolidin-5-yl]-propionic acid tert-butyl ester

(486) Starting from intermediate BA.ii (3.25 g) and following procedure I, the title compound was obtained as a colourless solid (3.27 g; 95% yield).

(487) MS (ESI, m/z): 509.1 [M+H.sup.+].

BA.iv. 6-{5-[(1RS)-1-(tert-butyl-dimethyl-silanyloxy)-3-hydroxy-propyl]-((5RS)-2-oxo-oxazolidin-3-yl)}-4H-benzo[1,4]thiazin-3-one

(488) Starting from intermediate BA.iii (1.01 g) and following procedure A, the title compound was obtained, after CC (Hept/EA 2:1 then 0:1), as a colourless foam (205 mg; 23% yield).

(489) MS (ESI, m/z): 439.1 [M+H.sup.+].

Preparation BB: (R)-6-amino-7-fluoro-2-methoxy-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

BB.i. 6-fluoro-2,3-dimethoxy-quinoxaline-5-carbaldehyde

(490) A solution of tetramethylpiperidine (16.4 mL) in dry THF (100 mL) was cooled to −78° C. and treated dropwise with n-BuLi (2.5M in Hex; 39 mL). The solution was further stirred at −78° C. for 30 min. A solution of 6-fluoro-2,3-dimethoxy-quinoxaline (15.6 g; prepared from the commercially available 2,3-dichloro-6-fluoroquinoxaline according to Egyptian Journal of Chemistry (1980), Volume Date 1977, 20, 427-39) in dry THF (450 mL) was cooled to −78° C., treated dropwise with the first solution and further stirred at −78° C. for 30 min. The resulting reaction mixture was treated with DMF (11.56 mL) and further stirred at −78° C. for 15 min. The reaction mixture was poured onto a mixture of a sat. NH.sub.4Cl solution and ice and extracted with ether. The org. layer was washed with brine, dried over MgSO.sub.4, evaporated under reduced pressure and crystallised from Hex/EA affording a light yellow solid (12.5 g; 71% yield).

(491) .sup.1H NMR (CDCl.sub.3) δ: 11.10 (d, J=0.6 Hz, 1H), 7.96 (dd, J=9.1, 5.3 Hz, 1H), 7.30 (m, 1H), 4.19 (m, 3H), 4.15 (m, 3H).

BB.ii. 6-fluoro-2,3-dimethoxy-5-vinyl-quinoxaline

(492) A suspension of methyltriphenylphosphonium bromide (18.15 g) in THF (200 mL) was treated with tBuOK (5.7 g). After stirring for 1 h, the solution was cooled to 0° C. and treated with a solution of intermediate BB.i (10.0 g) in THF (100 mL). The reaction mixture was further stirred at rt for 3 h and sequentially washed with water and with a sat. NH.sub.4Cl solution. The org. layer was dried over MgSO.sub.4, evaporated and purified by CC (Hex/EA 4:1 to 2:1), affording a colourless solid (8.80 g; 89% yield).

(493) .sup.1H NMR (CDCl.sub.3) δ: 7.62 (dd, J=8.8, 5.3 Hz, 1H), 7.46 (m, 1H), 7.25 (m, 1H), 6.34 (m, 1H), 5.69 (m, 1H), 4.17 (s, 3H), 4.13 (s, 3H).

BB.iii. (S)-1-(6-fluoro-2,3-dimethoxy-quinoxalin-5-yl)-ethane-1,2-diol

(494) Starting from intermediate BB.ii (8.70 g) and using procedure L with AD-mix α, the title compound was obtained as a beige solid (5.60 g; 56% yield) after crystallization from ether.

(495) .sup.1H NMR (DMSO d6) δ: 7.67 (dd, J=9.1, 5.6 Hz, 1H), 7.35 (dd, J=10.3, 9.1 Hz, 1H), 5.56 (m, 1H), 5.20 (d, J=6.4 Hz, 1H), 4.73 (t, J=6.2 Hz, 1H), 4.05 (s, 3H), 4.01 (s, 3H), 3.87 (m, 1H), 3.69 (m, 1H).

BB.iv. (S)-2-(tert-butyl-dimethyl-silanyloxy)-1-(6-fluoro-2,3-dimethoxy-quinoxalin-5-yl)-ethanol

(496) Starting from intermediate BB.iii (5.50 g) and using procedure M, the title compound was obtained, after purification by CC (Hept/EA 2:1), as a yellow oil (7.40 g; 94% yield).

(497) MS (ESI, m/z): 383.2 [M+H.sup.+].

BB.v. [(R)-2-(tert-butyl-dimethyl-silanyloxy)-1-(6-fluoro-2,3-dimethoxy-quinoxalin-5-yl)-ethyl]-carbamic acid tert-butyl ester

(498) Starting from intermediate BB.iv (7.30 g) and using procedure N′, the title compound was obtained, after purification by CC (Hept/EA 9:1 t 4:1), as a yellow oil (6.7 g, 73% yield).

(499) .sup.1H NMR (CDCl.sub.3) δ: 7.66 (dd, J=9.1, 5.6 Hz, 1H), 7.23 (m, 1H), 6.50 (m, 1H), 4.17 (s, 3H), 4.13 (s, 3H), 3.92 (d, J=6.4 Hz, 2H), 1.42 (s, 9H), 0.76 (s, 9H), −0.09 (s, 3H), −0.14 (s, 3H).

BB.vi. [(R)-1-(6-fluoro-2,3-dimethoxy-quinoxalin-5-yl)-2-hydroxy-ethyl]-carbamic acid tert-butyl ester

(500) Starting from intermediate BB.v (6.70 g) and using procedure J, the title compound was obtained, after crystallization from Hept/EA 1:1, as a courless solid (3.60 g; 70% yield).

(501) .sup.1H NMR (CDCl.sub.3) δ: 7.69 (dd, J=9.1, 5.6 Hz, 1H) 7.26 (m, 1H), 6.60 (m, 1H), 5.80 (m, 1H), 4.17 (s, 3H), 4.13 (s, 3H), 3.95 (m, 2H), 1.43 (s, 9H).

BB.vii. ((R)-7-fluoro-2-methoxy-3-oxo-5,6-dihydro-3H-pyrrolo[1,2,3-de]quinoxalin-6-yl)-carbamic acid tert-butyl ester

(502) Starting from intermediate BB.vi (3.50 g) and using procedure H, the intermediate mesylate was formed. The reaction mixture was further stirred at reflux for 12 h, cooled to rt, washed with water. The org. layer was dried over MgSO.sub.4 and concentrated under reduced pressure affording a crude solid (2.70 g, 84% yield) containing the title compound in a 3:2 mixture with (R)-4-(6-fluoro-2,3-dimethoxy-quinoxalin-5-yl)-oxazolidin-2-one. The mixture was used without any further purification in the next step.

BB.viii. (R)-6-amino-7-fluoro-2-methoxy-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

(503) Starting from intermediate BB.vii (2.70 g) and using procedure B, the title compound was obtained after purification by CC (EA/MeOH 9:1 containing 1% NH.sub.4OH) as a colourless solid (469 mg; 25% yield).

(504) MS (ESI, m/z): 236.2 [M+H.sup.+].

Preparation BC: (R)-1-amino-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(505) The title compound was prepared in analogy to Preparation AS, using however AD-mix α in the second step.

(506) The analytical data were identical with those of the compound of Preparation AS.

Preparation BD: toluene-4-sulfonic acid (R)-4-hydroxy-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de][1,5]naphthyridin-4-ylmethyl ester

BD.i. 2-(6-methoxy-[1,5]naphthyridin-4-yl)-propane-1,3-diol

(507) A solution of 2-methoxy-8-methyl-1,5-naphthyridine (2.90 g; prepared according to WO 00/21948) in aq. formaldehyde (37%; 7.8 mL) was heated at 100° C. for 3 days. After cooling to rt, the reaction mixture was concentrated to dryness and the residue was taken up in MeOH (10 mL) and concentrated again. The residue was purified by CC (DCM/MeOH/NH.sub.4OH 1000:100:8) to give a colourless solid (2.78 g; 71% yield).

(508) .sup.1H NMR (DMSO-d.sub.6) δ: 8.67 (d, J=4.4 Hz, 1H), 8.22 (d, J=9.1 Hz, 1H), 7.51 (d, J=4.4 Hz, 1H), 7.22 (d, J=9.1 Hz, 1H), 4.56 (m, 2H), 4.00 (m, 4H), 3.84 (m, 4H).

BD.ii. Acetic acid (S)-3-hydroxy-2-(6-methoxy-[1,5]naphthyridin-4-yl)-propyl ester

(509) A solution of intermediate BD.i (1.34 g) in vinyl acetate (10 mL) was treated with powdered 3 Å molecular sieves (78 mg) and stirred at rt for 15 min under an atmosphere of nitrogen. Lipase acrylic resin from Candida antarctica (600 mg, Sigma L4777) was added and stirring was continued for 4 h at rt. The polymer bound enzyme was filtered off, the filter cake was rinsed with THF and the filtrate was concentrated. The residue was purified by CC (DCM/MeOH/NH.sub.4OH 1000:25:2), affording a colourless oil (0.688 g; 44% yield).

(510) .sup.1H NMR (CDCl.sub.3) δ: 8.72 (d, J=4.7 Hz, 1H), 8.23 (d, J=9.1 Hz, 1H), 7.46 (d, J=4.7 Hz, 1H), 7.15 (d, J=9.1 Hz, 1H), 4.64 (m, 2H), 4.24 (m, 1H), 4.08 (m, 5H), 2.05 (s, 3H).

BD.iii. Acetic acid (S)-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de][1,5]naphthyridin-4-ylmethyl ester

(511) A solution of intermediate BD.ii (2.05 g) in DCM (40 mL) was transformed into the corresponding mesylate using procedure H. After full consumption of the alcohol, DCE (40 mL) was added and the solution was further stirred at 60° C. for 4 h. After cooling to rt, water was added and the two layers were decanted and the aq. layer was extracted once more with DCM. The combined org. layers were concentrated to dryness. The residue was triturated with TBME, affording a grey solid (1.40 g; 77% yield).

(512) .sup.1H NMR (CDCl.sub.3) δ: 8.53 (d, J=4.7 Hz, 1H), 7.93 (d, J=9.7 Hz, 1H), 7.34 (dd, J=4.7, 0.9 Hz, 1H), 6.90 (d, J=9.7 Hz, 1H), 4.57 (dd, J=12.9, 9.4 Hz, 1H), 4.37 (d, J=6.4 Hz, 2H), 4.27 (dd, J=13.2, 5.0 Hz, 1H), 4.09 (m, 1H), 2.06 (s, 3H).

BD.iv. (S)-4-hydroxymethyl-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(513) To a solution of intermediate BD.iii (1.11 g) in MeOH (30 mL), cooled to −10° C., K.sub.2CO.sub.3 (313 mg, 0.5 eq.) was added and the mixture was vigorously stirred at 0° C. for 20 min. The mixture was concentrated and the residue was purified by CC (DCM/MeOH/NH.sub.4OH 1000:100:8), affording a colourless solid (773 mg; 84% yield).

(514) MS (ESI, m/z): 203.0 [M+H.sup.+].

BD.v. Methanesulfonic acid (S)-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de][1,5]naphthyridin-4-ylmethyl ester

(515) A solution of intermediate BD.iv (600 mg) in DCM (30 mL) was transformed into the corresponding mesylate using procedure H. The crude material (1.03 g) was used in the next step without any further purification.

(516) MS (ESI, m/z): 281.2 [M+H.sup.+].

BD.vi. 4-methylene-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(517) A solution of intermediate BD.v (1.03 g) in DMF (10 mL) was stirred at rt in the presence of DBU (1.12 mL) for 2 h. The reaction mixture was diluted with EA and water. The aq. layer was extracted with EA (2×100 mL) and DCM/MeOH (3×50 mL; 9:1). The combined org. layers were sequentially washed with water and brine and dried over MgSO.sub.4. The solvent was evaporated under reduced pressure, affording a yellow solid (490 mg; 72% yield).

(518) .sup.1H NMR (CDCl.sub.3) δ: 8.55 (d, J=5.0 Hz, 1H), 7.96 (d, J=9.7 Hz, 1H), 7.44 (d, J=5.0 Hz, 1H), 6.92 (d, J=9.7 Hz, 1H), 6.00 (td, J=2.9, 0.9 Hz, 1H), 5.65 (td, J=2.6, 0.9 Hz, 1H), 5.02 (t, J=2.6 Hz, 2H).

BD.vii. (R)-4-hydroxy-4-hydroxymethyl-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(519) A solution of intermediate BD.vi (240 mg) was dihydroxylated in presence of AD-mix α using procedure L. The crude yellow solid (216 mg; 76% yield) was used in the next step without any further purification.

(520) .sup.1H NMR (CDCl.sub.3) δ: 8.55 (d, J=4.7 Hz, 1H), 7.90 (m, 1H), 7.53 (d, J=4.7 Hz, 1H), 6.81 (m, 1H), 4.35 (m, 2H), 3.89 (m, 3H).

BD.viii. Toluene-4-sulfonic acid (R)-4-hydroxy-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de][1,5]naphthyridin-4-ylmethyl ester

(521) A solution of intermediate BD.vii (210 mg) was stirred at rt overnight in presence of TEA (0.20 mL), TsCl (185 mg) and dibutyltin oxide (12 mg). The reaction mixture was diluted with water (3 mL). The org. layer was washed with sat. NaHCO.sub.3 and brine and dried over MgSO.sub.4. The solvent was evaporated under reduced pressure, affording an off-white solid (172 mg; 48% yield).

(522) MS (ESI, m/z): 373.0 [M+H.sup.+].

Preparation BE: rac-1-amino-9-bromo-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

BE.i. (7-bromo-2-methoxy-quinolin-8-yl)-methanol

(523) A suspension of 7-bromo-8-bromomethyl-2-(methyloxy)quinoline (35.2 g; prepared according to WO 2007/081597; containing 20% of debrominated compound) in acetone/water (1:1; 860 mL) was refluxed for 6 h in presence of NaHCO.sub.3 (14.63 g). The org. solvent was removed under reduced pressure and the residue was extracted with EA. The org. layer was washed with brine and dried over Na.sub.2SO.sub.4. The solvent was then evaporated and the residue was crystallized from TBDME, affording an off-white solid (16.0 g; 56% yield).

(524) MS (ESI, m/z): 268.0 [M+H.sup.+].

BE.ii. 7-bromo-2-methoxy-quinoline-8-carbaldehyde

(525) A solution of oxalyl chloride (9.47 mL) in DCM (200 mL) was cooled to −78° C. and treated dropwise with a solution of DMSO (9.52 mL) in DCM (80 mL). After stirring for 15 min, the solution was treated with a solution of intermediate BE.i (10.0 g) in DCM (80 mL). After further stirring at −78° C. for 3 h, the reaction mixture was treated dropwise with a solution of TEA (39.0 mL) in DCM (80 mL) over 1 h. The reaction mixture was further stirred for 40 min and allowed to reach rt. The reaction mixture was than treated with a sat. NaHCO.sub.3 solution. The org. layer was separated and washed with brine, dried over Na.sub.2SO.sub.4. The solvent was evaporated and the residue was dissolved in EA and filtered through a pad of silica gel, affording a pale yellow solid (3.74 g; 38% yield).

(526) .sup.1H NMR (DMSO-d.sub.6) δ: 11.06 (s, 1H), 8.36 (d, J=8.8 Hz, 1H), 8.04 (d, J=8.8 Hz, 1H), 7.74 (m, 1H), 7.17 (d, J=8.8 Hz, 1H), 4.01 (s, 4H).

BE.iii. 7-bromo-2-methoxy-8-vinyl-quinoline

(527) To a solution of methyltriphenylphosphonium bromide (1.00 g) in THF (8 mL) cooled to −78° C. was added n-BuLi (2.5M in Hex, 1.09 mL, 1.5 eq.). The mixture was stirred 15 min at this temperature and then 45 min at 0° C. before cooling again to −78° C. A solution of intermediate BE.ii (500 mg) in THF (8 mL) was quickly added. The reaction proceeded overnight with gradual warming to rt. MeOH was added to quench the reaction and the mixture was concentrated under reduced pressure. The residue was purified by CC (Hept/EA 4:1 to 2:1), affording the title compound as a yellowish oil (411 mg; 83% yield).

(528) MS (ESI, m/z): 264.3 [M+H.sup.+].

BE.iv. rac-1-(7-bromo-2-methoxy-quinolin-8-yl)-ethane-1,2-diol

(529) Starting from intermediate BE.iii (5.50 g) and proceeding in analogy to Preparation AX, step AX.ii, using however K.sub.2OsO.sub.4/NMO instead of AD-mix β and omitting the use of methylsulfonamide, the title compound was obtained as a beige solid (5.75 g, 93% yield) after crystallization from TBDME.

(530) .sup.1H NMR (CDCl.sub.3) δ: 8.01 (d, J=9.1 Hz, 1H), 7.58 (m, 1H), 7.50 (m, 1H), 6.97 (m, 1H), 5.53 (m, 1H), 4.07 (s, 3H), 3.91 (m, 2H).

BE.v. rac-1-(7-bromo-2-methoxy-quinolin-8-yl)-2-(tert-butyl-dimethyl-silanyloxy)-ethanol

(531) Starting from intermediate BE.iv (5.70 g) and using procedure M, the title compound was obtained as a brown oil (7.79 g, 99% yield).

(532) .sup.1H NMR (CDCl.sub.3) δ: 7.97 (d, J=8.8 Hz, 1H), 7.55 (m, 1H), 7.45 (m, 1H), 6.93 (d, J=8.8 Hz, 1H), 5.54 (t, J=5.6 Hz, 1H), 4.12 (m, 1H), 4.04 (s, 3H), 3.98 (m, 1H), 0.75 (m, 9H), −0.14 (d, J=0.9 Hz, 6H).

BE.vi. rac-1-(7-bromo-2-methoxy-quinolin-8-yl)-2-(tert-butyl-dimethyl-silanyloxy)-ethylamine

(533) Starting from intermediate BE.v (7.75 g), the title compound was prepared in analogy to Preparation Z, step Z.iv. A yellow oil (2.6 g; 33% yield) was obtained.

(534) MS (ESI, m/z): 411.3 [M+H.sup.+].

BE.vii. rac-[1-(7-bromo-2-methoxy-quinolin-8-yl)-2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-carbamic acid tert-butyl ester

(535) Starting from intermediate BE.vi (2.60 g) and using procedure G, the title compound was obtained as a yellow oil (3.20 g, 99% yield).

(536) .sup.1H NMR (CDCl.sub.3) δ: 7.95 (d, J=9.1 Hz, 1H), 7.55 (m, 1H), 7.44 (m, 1H), 6.92 (d, J=9.1 Hz, 1H), 6.35 (m, 1H), 4.97 (m, 1H), 4.06 (m, 3H), 4.03 (m, 1H), 3.74 (m, 1H), 1.25 (m, 9H), 0.75 (s, 9H), −0.11 (s, 6H).

BE.viii. rac-[1-(7-bromo-2-methoxy-quinolin-8-yl)-2-hydroxy-ethyl]-carbamic acid tert-butyl ester

(537) Starting from intermediate BE.vii (3.20 g) and using procedure J, the title compound was obtained as an off-white solid (1.70 g, 68% yield).

(538) .sup.1H NMR (CDCl.sub.3) δ: 7.98 (d, J=9.1 Hz, 1H), 7.60 (m, 1H), 7.49 (m, 1H), 6.96 (d, J=8.8 Hz, 1H), 5.92 (m, 1H), 4.08 (m, 4H), 4.03 (m, 2H), 1.44 (s, 9H).

BE.ix. rac-(9-bromo-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-carbamic acid tert-butyl ester

(539) Starting from intermediate BE.viii (400 mg) and using the same procedure as for the preparation of intermediate Z.vi, the title compound was obtained as a yellow solid (372 mg, 100% yield).

(540) .sup.1H NMR (CDCl.sub.3) δ: 7.67 (d, J=9.4 Hz, 1H), 7.32 (m, 2H), 6.68 (m, 1H), 5.58 (m, 1H), 4.97 (m, 1H), 4.64 (m, 1H), 4.32 (m, 1H), 1.24 (m, 9H).

(541) MS (ESI, m/z): 365.3 [M+H.sup.+].

BE.x. rac-1-amino-9-bromo-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(542) Starting from intermediate BE.ix (100 mg) and using procedure B, the title compound was obtained as an off-white solid (52 mg, 72% yield).

(543) .sup.1H NMR (CDCl.sub.3) δ: 7.67 (d, J=9.7 Hz, 1H), 7.33 (m, 2H), 6.68 (d, J=9.7 Hz, 1H), 4.89 (dd, J=8.8, 3.5 Hz, 1H), 4.62 (dd, J=13.5, 8.5 Hz, 1H), 4.17 (dd, J=13.5, 3.8 Hz, 1H), 1.80 (m, 2H).

Preparation BF: (R)-1-amino-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-7-carboxylic acid ethyl ester

BF.i. 2-methoxy-8-vinyl-quinoline-5-carboxylic acid ethyl ester

(544) A solution of vinylboronic anhydride pyridine complex (1:1; 3.81 g) in DMF (240 mL) was treated with tetrakis(triphenylphosphine)palladium(0) (731 mg) and stirred under nitrogen for 20 min. The reaction mixture was sequentially treated with K.sub.2CO.sub.3 (4.372 g) water (73 mL) and 2-methoxy-8-[[(trifluoromethyl)sulfonyl]oxy]-5-quinoline carboxylic acid ethyl ester (12.0 g; prepared in analogy to the corresponding n-butyl ester described in WO 2006/046552) and further stirred at 85° C. overnight. The reaction mixture was diluted with water and extracted with ether. The org. layer was dried over MgSO.sub.4, concentrated to dryness and purified by CC (Hex/EA, 4:1), affording a yellow oil (5.40 g; 66% yield).

(545) .sup.1H NMR (CDCl.sub.3) δ: 9.20 (d, J=9.1 Hz, 1H), 8.08 (dd, J=7.9, 0.6 Hz, 1H), 7.96 (dd, J=18.2, 11.1 Hz, 1H), 7.86 (d, J=7.9 Hz, 1H), 7.02 (d, J=9.4 Hz, 1H), 6.05 (dd, J=18.2, 1.5 Hz, 1H), 5.54 (dd, J=11.1, 1.5 Hz, 1H), 4.45 (q, J=7.3 Hz, 2H), 4.10 (s, 3H), 1.45 (t, J=7.0 Hz, 3H).

BF.ii. 8-((S)-1,2-dihydroxy-ethyl)-2-methoxy-quinoline-5-carboxylic acid ethyl ester

(546) A solution of intermediate BF.i (5.40 g) was dihydroxylated in the presence of AD-mix α using procedure L. After crystallization from ether, the product was obtained as a white solid (4.30 g; 70% yield; enantiomeric excess not checked, assumed 100%).

(547) .sup.1H NMR (DMSO d6) δ: 9.05 (d, J=9.4 Hz, 1H), 8.04 (m, 1H), 7.87 (d, J=7.9 Hz, 1H), 7.15 (d, J=9.4 Hz, 1H), 5.66 (m, 1H), 5.35 (m, 1H), 4.67 (m, 1H), 4.37 (q, J=7.0 Hz, 2H), 4.00 (s, 3H), 3.79 (m, 1H), 3.43 (m, 1H), 1.35 (t, J=7.3 Hz, 3H)

BF.iii. 8-[(S)-2-(tert-butyl-dimethyl-silanyloxy)-1-hydroxy-ethyl]-2-methoxy-quinoline-5-carboxylic acid ethyl ester

(548) Starting from intermediate BF.ii (4.20 g) and using procedure M, the title intermediate was obtained as a yellow oil (5.48 g; 94% yield).

(549) MS (ESI, m/z): 406.2 [M+H.sup.+].

BF.iv. 8-[(R)-1-tert-butoxycarbonylamino-2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-2-methoxy-quinoline-5-carboxylic acid ethyl ester

(550) A solution of intermediate BF.iii (5.30 g) and PPh.sub.3 (4.11 g) in THF (130 mL) was cooled to 0° C. and treated dropwise with DPPA (3.4 mL) and DIAD (3.36 mL). The reaction mixture was stirred at 0° C. for 15 min than at rt for 1.5 h. The reaction mixture was evaporated to dryness and purified by CC (Hept/EA 2:1), affording the intermediate azide as a yellow oil (6.0 g). The latter was dissolved in THF/water (9:1; 50 mL), treated with PPh.sub.3 (4.1 g) and stirred at 50° C. for 1.5 h. The reaction mixture was then reacted with Boc.sub.2O (5.7 g) and further stirred at rt over the weekend. The reaction mixture was concentrated under reduced pressure and purified by CC (Hept/EA 9:1 to 4:1), affording a yellow oil (9.20 g; contaminated by remaining Boc.sub.2O).

(551) .sup.1H NMR (CDCl.sub.3) δ: 9.21 (d, J=9.4 Hz, 1H), 8.05 (d, J=7.9 Hz, 1H), 7.59 (d, J=7.6 Hz, 1H), 7.01 (d, J=9.4 Hz, 1H), 5.64 (t, J=4.7 Hz, 1H), 4.44 (q, J=7.0 Hz, 2H), 4.07 (m, 5H), 1.50 (m, 3H), 1.44 (s, 9H), 0.76 (s, 9H), −0.23 (m, 6H).

BF.v. 8-((R)-1-tert-butoxycarbonylamino-2-hydroxy-ethyl)-2-methoxy-quinoline-5-carboxylic acid ethyl ester

(552) Starting from intermediate BF.iv (6.56 g) and using procedure J, the title intermediate was obtained as a colourless solid (2.60 g; 51% yield).

(553) .sup.1H NMR (CDCl.sub.3) δ: 9.22 (d, J=9.4 Hz, 1H), 8.06 (d, J=7.6 Hz, 1H), 7.62 (d, J=7.9 Hz, 1H), 7.04 (d, J=9.4 Hz, 1H), 5.55 (m, 1H), 4.44 (q, J=7.3 Hz, 2H), 4.03 (m, 5H), 1.44 (s, 9H).

BF.vi. (R)-1-tert-butoxycarbonylamino-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-7-carboxylic acid ethyl ester

(554) Starting from intermediate BF.v (2.40 g) and using procedure H, the title intermediate was obtained as a colourless solid after trituration in ether (2.10 g; 95% yield).

(555) MS (ESI, m/z): 359.2 [M+H.sup.+].

BF.vii. (R)-1-amino-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-7-carboxylic acid ethyl ester

(556) Starting from intermediate BF.vi (1.00 g) and using procedure B, the title compound was obtained as a beige solid (690 mg; 96% yield).

(557) MS (ESI, m/z): 259.2 [M+H.sup.+].

Preparation BG: (R)-1-amino-7-hydroxymethyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

BG.i. ((R)-7-hydroxymethyl-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-carbamic acid tert-butyl ester

(558) Starting from intermediate BF.vi (250 mg) and using procedure A, the title intermediate was obtained as a yellowish solid after trituration in ether (190 mg; 86% yield).

(559) MS (ESI, m/z): 317.2 [M+H.sup.+].

BG.ii. (R)-1-amino-7-hydroxymethyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(560) Starting from intermediate BG.i (180 mg) and using procedure B, the title compound was isolated from the water phase after evaporation to dryness and suspension in DCM/MeOH (9:1), affording 400 mg of a beige solid (contaminated by inorganic salts). The material was used without any further purification in the next steps.

(561) .sup.1H NMR (DMSO d6) δ: 8.10 (d, J=9.7 Hz, 1H), 7.65 (d, J=7.6 Hz, 1H), 7.27 (d, J=7.6 Hz, 1H), 6.61 (d, J=9.7 Hz, 1H), 5.41 (m, 1H), 5.19 (m, 1H), 4.79 (m, 2H), 4.55 (dd, J=13.5, 8.5 Hz, 1H), 4.22 (dd, J=13.5, 3.2 Hz, 1H), 4.07 (ddd, J=3.2, 2.1, 0.9 Hz, 1H).

Preparation BH: (R)-1-amino-7-dimethylaminomethyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

BH.i. ((R)-7-formyl-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-carbamic acid tert-butyl ester

(562) A solution of intermediate BG.i (640 mg) in DCM/THF (40 mL; 2:1) was stirred in the presence of MnO.sub.2 (3.75 g) for 30 min. The reaction mixture was filtered through Celite® and the filtrate was evaporated to dryness. The residue was triturated in ether/Hept, affording a yellow solid (480 mg; 75% yield).

(563) .sup.1H NMR (CDCl.sub.3) δ: 10.19 (s, 1H), 8.84 (d, J=9.7 Hz, 1H), 7.69 (m, 2H), 6.81 (d, J=9.7 Hz, 1H), 5.66 (m, 1H), 5.11 (m, 1H), 4.74 (dd, J=13.8, 9.1 Hz, 1H), 4.25 (m, 1H), 1.45 (m, 9H).

BH.ii. ((R)-7-dimethylaminomethyl-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-carbamic acid tert-butyl ester

(564) Starting from intermediate BH.i (200 mg) and NHMe.sub.2 (0.11 mL; 5.6M in EtOH) and using procedure E, the title intermediate was obtained as a yellow solid (140 mg; 64% yield).

(565) MS (ESI, m/z): 344.6 [M+H.sup.+].

BH.iii. (R)-1-amino-7-dimethylaminomethyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(566) Starting from intermediate BH.ii (140 mg) and using procedure B, the title compound was obtained as an orange oil (74 mg; 76% yield).

(567) MS (ESI, m/z): 244.3 [M+H.sup.+].

Preparation BI: (R)-1-amino-7-pyrrolidin-1-ylmethyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

BI.i. ((R)-4-oxo-7-pyrrolidin-1-ylmethyl-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-carbamic acid tert-butyl ester

(568) Starting from intermediate BH.i (200 mg) and pyrrolidine (52 μL) and using procedure E, the title intermediate was obtained as a yellow solid (190 mg; 80% yield).

(569) MS (ESI, m/z): 370.4 [M+H.sup.+].

BI.ii. (R)-1-amino-7-pyrrolidin-1-ylmethyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(570) Starting from intermediate BI.i (190 mg) and using procedure B, the title compound was obtained as an orange oil (100 mg; 72% yield).

(571) MS (ESI, m/z): 269.9 [M+H.sup.+].

Preparation BJ: 3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propionaldehyde

(572) The title compound was prepared in analogy to Preparation AR, starting however from (S)-2-[2-[[(tert-butyl)dimethylsilyl]oxy]propyl]-oxirane. The yields were similar and the analytical data (MS, .sup.1H NMR) were identical.

Preparation BK: 3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propionaldehyde

BK.i. (2-tert-butoxycarbonylamino-6-chloro-pyridin-3-ylsulfanyl)-acetic acid ethyl ester

(573) A solution of TMEDA (1.677 mL) in THF (20 mL) was cooled to −20° C. and treated dropwise with 2.3M n-BuLi (4.75 mL). After stirring at this temperature for 20 min, the solution was cooled to −78° C. and treated dropwise with a solution of 2-tert-butoxycarbonylamino-6-chloropyridine (1.14 g; commercial) in THF (7.5 mL). The solution was further stirred at this temperature for 1 h and treated with sulfur (S8). After further stirring at this temperature for 20 min the reaction mixture was treated with ethyl bromoacetate (0.86 mL). After further stirring for 2 h at −78° C., the temperature was allowed to reach −45° C. and quenched by the addition of EA and water. The org phase was sequentially washed with 1N HCl, conc. NH.sub.4Cl solution and brine. The org. phase was dried over MgSO.sub.4 and the solvents were evaporated. The residue was purified by CC (Hept/EA 4:1 to 2:1), affording a colourless oil (1.05 g; 60% yield).

(574) .sup.1H NMR (CDCl.sub.3) δ: 8.01 (s, 1H), 7.79 (d, J=8.2 Hz, 1H), 6.98 (d, J=8.2 Hz, 1H), 4.14 (q, J=7.0 Hz, 3H), 3.47 (s, 2H), 1.54 (s, 12H), 1.22 (t, J=7.0 Hz, 3H).

BK.ii. 6-chloro-4H-pyrido[3,2-b][1,4]thiazin-3-one

(575) A solution of intermediate BK.i (1.0 g) in DCM (6 mL) was stirred at rt overnight in the presence of TFA (6 mL). The reaction mixture was evaporated to dryness and the residue was dissolved in EtOH and refluxed for 2 days. The reaction mixture was evaporated to dryness and the residue was taken up in EA and a sat. aq. NaHCO.sub.3 solution. The org. layer was washed with brine, dried over MgSO.sub.4, concentrated under reduced pressure and crystallized from ether/Hept, affording a yellow solid (400 mg; 69% yield).

(576) .sup.1H NMR (CDCl.sub.3) δ: 8.28 (d, J=1.5 Hz, 1H), 7.57 (dd, J=8.2, 0.6 Hz, 1H), 6.98 (d, J=8.2 Hz, 1H), 3.50 (m, 2H).

BK.iii. 6-{(R)-5-[3-(tert-butyl-dimethyl-silanyloxy)-propyl]-2-oxo-oxazolidin-3-yl}-4H-pyrido[3,2-b][1,4]thiazin-3-one

(577) A vial was charged with intermediate BK.ii (2 g), palladium(II)acetate (224 mg), DPEphos (1.08 g), potassium phosphate tribasic (powdered; 4.33 g) and intermediate AR.ii (3.1 g). Dioxane (dry, over molecular sieves, 50 mL) was then added using a syringe and the resulting suspension was sparged with argon for 5 min. The mixture was then heated in a sealed flask at 80° C. overnight. The residue was extracted with EA/water. The org. layer was washed with brine, dried over MgSO.sub.4 and concentrated. The residue was purified by CC (Hept/EA 2:1, 1:1) affording a yellowish solid (3.58 g; 84% yield).

(578) .sup.1H NMR (DMSO d6) δ: 10.81 (s, 1H), 7.77 (m, 1H), 7.66 (m, 1H), 4.71 (m, 1H), 4.20 (m, 1H), 3.69 (dd, J=10.5, 7.3 Hz, 1H), 3.62 (t, J=6.4 Hz, 2H), 3.51 (s, 2H), 1.74 (m, 2H), 1.56 (dd, J=9.4, 7.3 Hz, 2H), 0.85 (m, 9H), 0.02 (s, 6H).

BK.iv. 6-[(R)-5-(3-hydroxy-propyl)-2-oxo-oxazolidin-3-yl]-4H-pyrido[3,2-b][1,4]thiazin-3-one

(579) Starting from intermediate BK.iii (3.58 g) and using procedure J, the title intermediate was obtained as a colourless solid (2.0 g; 76% yield).

(580) .sup.1H NMR (DMSO d6) δ: 10.83 (s, 1H), 7.77 (m, 1H), 7.66 (m, 1H), 4.70 (m, 1H), 4.48 (t, J=5.3 Hz, 1H), 4.20 (m, 1H), 3.70 (dd, J=10.3, 7.0 Hz, 1H), 3.51 (s, 2H), 3.43 (q, J=6.2 Hz, 2H), 3.28 (s, 3H), 1.75 (m, 2H), 1.51 (m, 2H).

BK.v. 3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propionaldehyde

(581) Starting from intermediate BK.iv (250 mg) and using the procedure of Preparation U, step U.iv, the title compound was obtained as a colourless solid (200 mg; 80% yield).

(582) MS (ESI, m/z): 308.3 [M+H.sup.+].

Preparation BL: 3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propionaldehyde

(583) The title compound was prepared in analogy to Preparation BK, starting however from (S)-2-[2-[[(tert-butyl)dimethylsilyl]oxy]propyl]-oxirane. The yields were similar and the analytical data (MS, .sup.1H NMR) were identical.

Preparation BM: (R)-4-amino-3-fluoro-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

BM.i. rac-1-(3-fluoro-6-methoxy-[1,5]naphthyridin-4-yl)-ethane-1,2-diol

(584) Starting from intermediate Ax.i (12.75 g) and proceeding in analogy to Preparation AX, step AX.ii, using however K.sub.2OsO.sub.4/NMO instead of AD-mix β and omitting the use of methylsulfonamide, the title compound was isolated as a light brown solid (9.80 g; 66% yield).

(585) MS (ESI, m/z): 238.4 [M+H.sup.+].

BM.ii. rac-2-(tert-butyl-dimethyl-silanyloxy)-1-(3-fluoro-6-methoxy-[1,5]naphthyridin-4-yl)-ethanol

(586) Starting from intermediate BM.i (12.35 g) and using procedure M, the title intermediate was obtained as a brown oil (18.85 g; 100% yield).

(587) MS (ESI, m/z): 353.4 [M+H.sup.+].

BM.iii. rac-8-[1-azido-2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-7-fluoro-2-methoxy-[1,5]naphthyridine

(588) Starting from intermediate BM.ii (18.85 g) and using procedure N, the title intermediate was obtained as an orange oil (22.2 g; contaminated with PPh.sub.3O).

(589) .sup.1H NMR (CDCl.sub.3) δ: 8.66 (d, J=1.5 Hz, 1H), 8.20 (d, J=9.1 Hz, 1H), 7.11 (d, J=9.1 Hz, 1H), 5.85 (m, 1H), 4.36 (m, 1H), 4.11 (m, 3H), 4.04 (m, 1H), 0.87 (s, 9H), 0.06 (d, J=8.8 Hz, 6H).

BM.iv. rac-2-azido-2-(3-fluoro-6-methoxy-[1,5]naphthyridin-4-yl)-ethanol

(590) Starting from intermediate BM.iii (20.0 g) and using procedure J, the title intermediate was obtained as a yellowish solid (13.76 g; 99% yield).

(591) .sup.1H NMR (CDCl.sub.3) δ: 8.69 (m, 1H), 8.23 (dd, J=9.1, 0.9 Hz, 1H), 7.13 (d, J=9.1 Hz, 1H), 5.92 (dd, J=7.9, 4.7 Hz, 1H), 4.29 (m, 1H), 4.11 (m, 3H), 4.06 (d, J=4.4 Hz, 1H), 1.25 (m, 1H).

BM.v. rac-4-azido-3-fluoro-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(592) Starting from intermediate BM.iv (17.75 g) and using procedure H, the title intermediate was obtained as an orange solid (7.94 g; 51% yield).

(593) .sup.1H NMR (CDCl.sub.3) δ: 8.45 (m, 1H), 7.88 (m, 1H), 6.84 (m, 1H), 5.66 (dd, J=8.5, 3.5 Hz, 1H), 4.62 (dd, J=13.8, 8.5 Hz, 1H), 4.35 (dd, J=13.8, 3.5 Hz, 1H).

BM.vi. (R)-4-amino-3-fluoro-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(594) A solution of intermediate BM.v (7.93 g) in THF (140 mL) was stirred at 60° C. for 3 h in the presence of PPh.sub.3 (9.90 g) and water (6.17 mL). The reaction mixture was concentrated to dryness and the residue was purified by CC (DCM/MeOH/NH.sub.4OH 1000:50:4 to 1000:100:8) affording, after stirring in TBME, (RS)-4-amino-3-fluoro-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one (6.37 g; 91% yield). This racemic material (6.22 g) was separated by preparative chiral HPLC using a 5 μm (R,R)-Whelk-01 column (50×250 mm) eluting with 4:1 MeCN-EtOH containing 0.1% of diethylamine, with t.sub.R=5.21 min for the title compound (compound of Preparation BM) and t.sub.R=6.13 min for the optical antipode (compound of Preparation BN). The recovery was 3.00 g (first eluting enantiomer, compound of Preparation BM, 100% ee) and 2.92 g (second eluting enantiomer, compound of Preparation BN, 100% ee).

(595) The absolute configuration of the title molecule was determined by X-ray analysis of the corresponding carboxamide obtained from (S)-mandelic acid.

(596) MS (ESI, m/z): 206.1 [M+H.sup.+]

Preparation BN: (S)-4-amino-3-fluoro-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(597) The title compound was obtained as the second eluting enantiomer (t.sub.R=6.13 min) at Preparation BM, step BM.vi.

(598) MS (ESI, m/z): 206.1 [M+H.sup.+].

Preparation BO: rac-1-amino-9-methyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

BO.i. (7-bromo-2-methoxy-quinolin-8-yl)-methanol

(599) A suspension of 7-bromo-8-bromomethyl-2-methoxyquinoline (35.2 g; prepared according to WO 2007/081597) and NaHCO.sub.3 (14.63 g) in acetone (430 mL) and water (430 mL) was refluxed for 6 h. The org. solvent was removed under reduced pressure and the aq. layer was extracted twice with EA. The combined org. layers were sequentially washed with water and brine and dried over Na.sub.2SO.sub.4. The solvent was removed under reduced pressure and the residue was crystallized from TBDME, affording an off-white solid (16.01 g; 56% yield).

(600) MS (ESI, m/z): 268.0 [M+H.sup.+].

BO.ii. 7-bromo-2-methoxy-quinoline-8-carbaldehyde

(601) A solution of oxalyl chloride (5.68 mL) in DCM (265 mL) was cooled to −78° C. and treated dropwise with a solution of DMSO (5.71 mL) in DCM (50 mL). The resulting solution was treated with a solution of intermediate BO.i (6.00 g) in DCM (50 mL). After stirring for 1 h at −78° C., the reaction mixture was treated with TEA (23.4 mL) in DCM (50 mL) and gradually allowed to reach rt. The reaction mixture was treated with sat. aq. NaHCO.sub.3 (300 mL) and the org. layer was separated and dried over Na.sub.2SO.sub.4. The solvent was evaporated under reduced pressure and the crude material was stirred in TBME, affording a yellow solid (4.68 g; 79% yield; contaminated by traces of starting material).

(602) MS (ESI, m/z): 266.0 [M+H.sup.+].

BO.iii. 7-bromo-2-methoxy-8-vinyl-quinoline

(603) Starting from intermediate BO.ii (500 mg) and methyltriphenylphosphonium bromide (1.01 g) and proceeding in analogy to Preparation Z, step Z.i, the title compound was obtained a colourless solid (411 mg; 83% yield).

(604) MS (ESI, m/z): 264.3 [M+H.sup.+].

BO.iv. rac-1-(7-bromo-2-methoxy-quinolin-8-yl)-ethane-1,2-diol

(605) Starting from intermediate BO.iii (5.50 g) and proceeding in analogy to Preparation AX, step AX.ii, using however K.sub.2OsO.sub.4/NMO instead of AD-mix β and omitting the use of methylsulfonamide, the title compound was obtained as a beige solid (5.75 g; 93% yield).

(606) .sup.1H NMR (CDCl3) δ: 8.01 (d, J=9.1 Hz, 1H), 7.58 (m, 1H), 7.50 (m, 1H), 6.97 (m, 1H), 5.53 (m, 1H), 4.07 (m, 3H), 3.91 (m, 2H).

BO.v. rac-1-(7-bromo-2-methoxy-quinolin-8-yl)-2-(tert-butyl-dimethyl-silanyloxy)-ethanol

(607) Starting from intermediate BO.iv (5.71 g) and using procedure M, the title compound was obtained as a brown oil (7.79 g; 99% yield).

(608) .sup.1H NMR (CDCl.sub.3) δ: 7.97 (d, J=8.8 Hz, 1H), 7.55 (m, 1H), 7.45 (m, 1H), 6.93 (d, J=8.8 Hz, 1H), 5.54 (t, J=5.6 Hz, 1H), 4.12 (m, 1H), 4.04 (s, 3H), 3.98 (m, 1H), 0.75 (m, 9H), −0.14 (d, J=0.9 Hz, 6H).

BO.vi. rac-8-[i-azido-2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-7-bromo-2-methoxy-quinoline

(609) Starting from intermediate BO.v (7.75 g) and using Procedure N, the title intermediate was obtained as a yellow oil (8.47 g; 100% yield).

(610) MS (ESI, m/z): 437.2 [M+H.sup.+].

BO.vii. rac-1-(7-bromo-2-methoxy-quinolin-8-yl)-2-(tert-butyl-dimethyl-silanyloxy)-ethylamine

(611) Starting from intermediate BO.vi. (8.45 g) and proceeding in analogy to Preparation BM, step BM.vi, the title intermediate was obtained as a yellow oil (2.60 g; 33% yield).

(612) MS (ESI, m/z): 411.3 [M+H.sup.+].

BO.viii. rac-[1-(7-bromo-2-methoxy-quinolin-8-yl)-2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-carbamic acid tert-butyl ester

(613) Starting from intermediate BO.vii (2.60 g) and using procedure G, the title intermediate was obtained as a yellow oil (3.20 g; 99% yield).

(614) .sup.1H NMR (CDCl.sub.3) δ: 7.95 (d, J=9.1 Hz, 1H), 7.55 (m, 1H), 7.44 (m, 1H), 6.92 (d, J=9.1 Hz, 1H), 6.35 (m, 1H), 4.97 (m, 1H), 4.06 (m, 3H), 4.03 (m, 1H), 3.74 (m, 1H), 1.25 (m, 9H), 0.75 (s, 9H), −0.11 (s, 6H).

BO.ix. rac-[1-(7-bromo-2-methoxy-quinolin-8-yl)-2-hydroxy-ethyl]-carbamic acid tert-butyl ester

(615) Starting from intermediate BO.viii (3.20 g) and using procedure J, the title intermediate was obtained as an off-white solid (1.70 g; 68% yield).

(616) MS (ESI, m/z): 396.9 [M+H.sup.+].

BO.x. rac-(9-bromo-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-carbamic acid tert-butyl ester

(617) Starting from intermediate BO.ix (400 mg) and using procedure H, the title intermediate was obtained as a yellow solid (372 mg; 100% yield).

(618) MS (ESI, m/z): 365.3 [M+H.sup.+].

BO.xi. rac-(9-methyl-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-carbamic acid tert-butyl ester

(619) A solution of intermediate BO.x (90 mg) in DME (1.5 mL) was treated with tetrakis-(triphenylphosphine)palladium and the solution was purged with N.sub.2. The solution was treated with K.sub.2CO.sub.3 (34 mg), water (0.5 mL) and trimethylboroxine (25 mg) and further stirred at 80° C. overnight. The reaction mixture was diluted with water and extracted with EA. The org. layer was sequentially washed with water, brine and dried over MgSO.sub.4. The solvent was removed under reduced pressure and the residue was purified by CC (EA), affording a colourless solid (82 mg; 100% yield).

(620) MS (ESI, m/z): 301.2 [M+H.sup.+].

BO.xii. rac-1-amino-9-methyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(621) Starting from intermediate BO.xi. (81 mg) and using procedure B, the title compound was obtained as a grey solid (34 mg; 79% yield).

(622) MS (ESI, m/z): 201.5 [M+H.sup.+].

Preparation BP: rac-4-[2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-butyraldehyde

BP.i. rac-6-[6-(tert-butyl-dimethyl-silanyloxy)-2-hydroxy-hexylamino]-4H-benzo[1,4]thiazin-3-one

(623) A solution of 2-[4-[(tert-butyl)dimethylsiloxy]butyl]oxirane (10.0 g) and 6-amino-4H-benzo[1,4]thiazin-3-one (7.81 g; commercial) in EtOH/water (300 mL; 9:1) was refluxed for 2 days. The solvents were removed under reduced pressure and the residue was taken up in EA/Hex (1:1; 100 mL) and filtered. The filtrate was concentrated under reduced pressure and purified by CC (EA/Hex; 1:1), affording an orange solid (7.40 g; 42% yield).

(624) MS (ESI, m/z): 411.3 [M+H.sup.+]

BP.ii. rac-6-{5-[4-(tert-Butyl-dimethyl-silanyloxy)-butyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]thiazin-3-one

(625) Starting from intermediate BP.i (7.30 g) and using procedure I, the title intermediate was obtained as a colourless solid (4.40 g; 79% yield).

(626) MS (ESI, m/z): 437.4 [M+H.sup.+].

BP.iii. rac-6-[5-(4-hydroxy-butyl)-2-oxo-oxazolidin-3-yl]-4H-benzo[1,4]thiazin-3-one

(627) Starting from intermediate BP.ii (4.40 g) and using procedure J, the title intermediate was obtained as a colourless solid (3.00 g; 92% yield).

(628) MS (ESI, m/z): 323.4 [M+H.sup.+].

BP.iv. rac-4-[2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-butyraldehyde

(629) Starting from intermediate BP.iii (3.0 g) and using the procedure of Preparation U, step U.iv, the title intermediate was obtained as a colourless solid (2.30 g; 77% yield).

(630) MS (ESI, m/z): 321.3 [M+H.sup.+].

Preparation BQ: rac-(1R*,2R*)-1-amino-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylic acid methyl ester

BQ.i. (E)-3-(2-methoxy-quinolin-8-yl)-acrylic acid methyl ester

(631) A solution of 8-bromo-2-methyloxyquinoline (10.0 g), Pd(OAc).sub.2 (311 mg), P(o-Tol).sub.3 (1.28 g) in DMF (100 mL) was treated with TEA (17.6 mL) and methyl acrylate (18.93 mL). The solution was purged 3 times with nitrogen and stirred at 120° C. for 1 h. The reaction mixture was diluted with water (200 mL) and extracted with ether/EA. The org. layer was washed with water (3×200 mL) and brine and dried over MgSO.sub.4. The solvent was removed under reduced pressure and the residue was purified by CC (Hept/EA 4:1), affording a pale yellow solid (9.34 g; 91% yield).

(632) .sup.1H NMR (CDCl.sub.3) δ: 8.00 (d, J=9.1 Hz, 1H), 7.66 (dd, J=7.9, 1.5 Hz, 1H), 7.57 (d, J=6.7 Hz, 1H), 7.36 (m, 1H), 6.92 (d, J=8.8 Hz, 1H), 6.24-6.05 (m, 2H), 4.84 (m, 1H), 4.10 (s, 3H), 3.89 (d, J=5.0 Hz, 1H), 3.78 (s, 3H), 1.43 (m, 9H).

BQ.ii. (2S*,3R*)-3-tert-butoxycarbonylamino-2-hydroxy-3-(2-methoxy-quinolin-8-yl)-propionic acid methyl ester

(633) A solution of tert-butyl carbamate (7.06 g) in n-propanol (120 mL) was sequentially treated with 0.4M NaOH (218 mL) and tert-butyl hypochlorite (10.6 mL; freshly prepared as described in Org. Lett. (2003), 5(12), 2123-2126 (S-2)). The reaction mixture was treated with a solution of (DHQD).sub.2PHAL (565 mg) and (DHQ).sub.2PHAL (565 mg) in n-propanol (100 mL) and after 5 min cooled to 10° C. and sequentially treated with a suspension of intermediate BQ.i. (7.07 g) in water/n-propanol (1:1; 140 mL) and potassium osmate(VI) dihydrate (428 mg). After stirring at +10° C. for 20 min the reaction mixture was treated with Na.sub.2SO.sub.3 (15 g) and further stirred at rt for 10 min. The reaction mixture was extracted with EA and the org. layer was sequentially washed with 5% aq. K.sub.2CO.sub.3, sat. aq. NaHCO.sub.3 and brine. After drying over MgSO.sub.4 and evaporation of the solvent, the residue was purified by CC (DCM/MeOH 10-1 containing 1% NH.sub.4OH), affording a pale yellow foam (6.85 g; 63% yield).

(634) MS (ESI, m/z): 377.6 [M+H.sup.+].

BQ.iii. rac-(1R*,2R*)-1-tert-butoxycarbonylamino-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylic acid methyl ester

(635) Starting from intermediate BQ.ii (7.80 g) and using procedure H, the title intermediate was obtained as a colourless solid (6.24 g; 87% yield).

(636) MS (ESI, m/z): 345.5 [M+H.sup.+].

BQ.iv. rac-(1R*,2R*)-1-amino-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylic acid methyl ester

(637) Starting from intermediate BQ.iii. (1.00 g) and using procedure B, the title compound was obtained as a colourless solid (684 mg; 96% yield).

(638) MS (ESI, m/z): 245.2 [M+H.sup.+].

Preparation BR: rac-(1R*,2R*)-1-amino-2-hydroxymethyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

BR.i. rac-((1R*,2R*)-2-hydroxymethyl-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-carbamic acid tert-butyl ester

(639) Starting from intermediate BQ.iii (3.20 g) and using procedure A, the title intermediate was obtained as a colourless solid (2.67 g; 91% yield).

(640) MS (ESI, m/z): 317.3 [M+H.sup.+].

BR.ii. rac-(1R*,2R*)-1-amino-2-hydroxymethyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(641) Starting from intermediate BR.i (600 mg) and using procedure B, the title compound was obtained as a colourless oil (400 mg; 98% yield).

(642) MS (ESI, m/z): 217.3 [M+H.sup.+].

Preparation BS: rac-(1R*,2R*)-1-amino-2-methoxymethyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

BS.i. rac-((1R*,2R*)-2-methoxymethyl-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-carbamic acid tert-butyl ester

(643) A solution of intermediate BR.i (400 mg) in THF (anhydrous; 4 mL) was treated at 0° C. with NaH (60% dispersion in oil; 51 mg). After a few min the reaction mixture was treated with MeI (83 μL) and further stirred at rt for 30 min. The reaction mixture was treated with sat. aq. NH.sub.4Cl and extracted with EA. The org. layer was washed with water and brine and dried over MgSO.sub.4. The solvent was evaporated under reduced pressure and the residue was purified by CC (DCM/MeOH/NH.sub.4OH 1000:50:4), affording a pale yellow solid (42 mg; 10% yield).

(644) MS (ESI, m/z): 331.2 [M+H.sup.+].

BS.ii. rac-(1R*,2R*)-1-amino-2-methoxymethyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(645) Starting from intermediate BS.i (42 mg) and using procedure B, the title compound was obtained as a pale yellow oil (28 mg; 96% yield).

(646) MS (ESI, m/z): 231.2 [M+H.sup.+].

Preparation BT: rac-(1R*,2S*)-1-amino-2-methyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

BT.i. rac-((1R*,2S*)-2-methyl-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-carbamic acid tert-butyl ester

(647) Starting from intermediate BR.i (800 mg) and using procedure H, the intermediate mesylate was formed and further reacted after usual work up. It was dissolved in DME (45 mL) and refluxed in presence of NaI (1.21 g). After 1.5 h the reaction mixture was treated with Bu.sub.3SnH (3 mL) and further refluxed for 3 h. The reaction mixture was diluted in ether and stirred in presence of 8% aq. KF for 16 h. The mixture was filtered. The two phases were separated and the aq. layer was extracted with EA. The combined org. layers were washed with water and brine and dried over MgSO.sub.4. The solvents were removed under reduced pressure and the residue was purified by CC (Hept/EA 1:1), affording a colourless solid (476 mg; 63% yield).

(648) MS (ESI, m/z): 301.3 [M+H.sup.+].

BT.ii. rac-(1R*,2S*)-1-amino-2-methyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(649) Starting from intermediate BT.i (467 mg) and using procedure B, the title compound was obtained as a yellow oil (274 mg; 88% yield).

(650) MS (ESI, m/z): 201.3 [M+H.sup.+].

Preparation BU: rac-(1R*,2R*)-1-amino-2-(1-hydroxy-1-methyl-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

BU.i. rac-[(1R*,2R*)-2-(1-hydroxy-1-methyl-ethyl)-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl]-carbamic acid tert-butyl ester

(651) A solution BQ.iii (422 mg) in THF (anhydrous; 8 mL) was treated dropwise at 0° C. with MeMgBr (1.4M in toluene/THF 3:1; 3.1 mL). After stirring 2 h at 0° C., the reaction mixture was allowed to reach rt and treated with MeMgBr (1.4M in toluene/THF 3:1; 5 mL). The reaction mixture was further stirred at rt overnight, quenched by the addition of sat. NH.sub.4Cl solution and extracted with EA. The org. layer was sequentially washed with water and brine and dried over MgSO.sub.4. The solvents were evaporated under reduced pressure and the residue was purified by CC (DCM/MeOH/NH.sub.4OH 1000:50:4), affording a pale yellow foam (74 mg; 17% yield).

(652) MS (ESI, m/z): 345.5 [M+H.sup.+].

BU.ii. rac-(1R*,2R*)-1-amino-2-(1-hydroxy-1-methyl-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(653) Starting from intermediate BU.i (74 mg) and using procedure B, the title compound was obtained as a brown oil (22 mg; 42% yield).

(654) MS (ESI, m/z): 245.3 [M+H.sup.+].

Preparation BV: rac-1-amino-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-9-carbonitrile

BV.i. rac-(9-cyano-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-carbamic acid tert-butyl ester

(655) A mixture of intermediate BE.ix (135 mg), Zn(CN).sub.2 (52 mg) and Pd(PPh.sub.3).sub.4 (21 mg) in DMF (2 mL) was heated at 110° C. overnight under argon in a sealed flask. After cooling to rt, the reaction mixture was diluted with water and extracted with EA. The org. layer was washed with water and brine and dried over MgSO.sub.4. The solvent was removed under reduced pressure and the residue was triturated in TBME, affording a pinkish solid (88 mg; 76% yield).

(656) MS (ESI, m/z): 312.3 [M+H.sup.+].

BV.ii. rac-1-amino-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-9-carbonitrile

(657) Starting from intermediate BV.i (88 mg) and using procedure B, the title compound was obtained as a colourless solid (57 mg, 95% yield).

(658) MS (ESI, m/z): 212.1 [M+H.sup.+].

Preparation BW: methanesulfonic acid (R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl ester

BWi. 6-[(R)-5-(tert-butyl-dimethyl-silanyloxymethyl)-2-oxo-oxazolidin-3-yl]-4H-pyrido[3,2-b][1,4]thiazin-3-one

(659) Starting from (5R)-5-[[[tert-butyldimethylsilyl]oxy]methyl]-2-oxazolidinone (1.20 g; prepared in according to Org. Letters (2005), 7, 1983-1985) and intermediate BK.ii (867 mg), the title compound was prepared in analogy to the preparation of intermediate BK.iii. After work-up and CC (Hept/EA 1:1), a beige solid (1.20 g; 70% yield) was obtained.

(660) .sup.1H NMR (CDCl.sub.3) δ: 7.90 (d, J=8.5 Hz, 1H), 7.80 (s, 1H), 7.60 (d, J=8.5 Hz, 1H), 4.67 (m, 1H), 4.11 (m, 2H), 3.90 (m, 1H), 3.78 (m, 1H), 3.48 (s, 2H), 0.84 (s, 9H), 0.07 (s, 6H).

BW.ii. 6-((R)-5-hydroxymethyl-2-oxo-oxazolidin-3-yl)-4H-pyrido[3,2-b][1,4]thiazin-3-one

(661) Starting from intermediate BW.i (1.20 g) and using procedure J, the title compound was obtained as a beige solid (880 mg; 100% yield).

(662) MS (ESI, m/z):282.3 [M+H.sup.+].

BW.iii. Methanesulfonic acid (R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl ester

(663) Starting from intermediate BW.ii (850 mg) and using procedure H, the title compound was obtained as a beige solid (850 mg; 78% yield).

(664) .sup.1H NMR (DMSO-d.sub.6) δ: 10.88 (s, 1H), 7.79 (m, 1H), 7.66 (m, 1H), 5.00 (m, 1H), 4.50 (m, 2H), 4.21 (m, 1H), 3.86 (dd, J=10.5, 6.2 Hz, 1H), 3.51 (s, 2H), 3.23 (s, 3H).

Preparation BX: methanesulfonic acid 2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethyl ester

BX.i. (S)-5-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-oxazolidin-2-one

(665) Starting from 2-[2-[[(tert-butyl)dimethylsilyl]oxy]ethyl]-oxirane, (7.00 g; prepared according to WO 2007/144423), carbamic acid ethyl ester (1.46 g), 4-nitrobenzoic acid (347 mg), (R,R)-(salen)Co.sup.II complex (626 mg) and NaH (1.676 g) and proceeding in analogy to Org. Letters (2005), 7, 1983-1985, the title compound was obtained as a dark orange solid (880 mg; 11% yield).

(666) .sup.1H NMR (DMSO-d.sub.6) δ: 7.39 (s, 1H), 4.59 (m, 1H), 3.67 (m, 2H), 3.53 (m, 1H), 3.13 (m, 1H), 1.79 (m, 2H), 0.85 (s, 9H), 0.02 (s, 6H).

BX.ii. 6-{(S)-5-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-2-oxo-oxazolidin-3-yl}-4H-pyrido[3,2-b][1,4]thiazin-3-one

(667) Starting from intermediate BX.i (880 mg) and intermediate BK.ii (720 mg), the title compound was prepared in analogy to the preparation of intermediate BK.iii. After work-up and CC (Hept/EA 1:1), a beige solid (1.00 g; 68% yield) was obtained.

(668) MS (ESI, m/z): 410.4 [M+H.sup.+].

BX.iii. 6-[(S)-5-(2-hydroxy-ethyl)-2-oxo-oxazolidin-3-yl]-4H-pyrido[3,2-b][1,4]thiazin-3-one

(669) Starting from intermediate BX.ii (1.00 g) and using procedure J, the title compound was obtained as a colourless solid (640 mg; 89% yield).

(670) MS (ESI, m/z): 296.4.3 [M+H.sup.+].

BX.iv. Methanesulfonic acid 2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethyl ester

(671) Starting from intermediate BX.iii (600 mg) and using procedure H, the title compound was obtained as a beige solid (649 mg; 81% yield).

(672) MS (ESI, m/z): 374.4 [M+H.sup.+].

Preparation BY: rac-1-amino-9-chloro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

BY.i. rac-(9-chloro-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-carbamic acid tert-butyl ester

(673) A suspension of intermediate BE.ix (140 mg), CuCl (152 mg) and pyridine (0.5 mL) in dry DMSO was heated at 120° C. for 1 h. After cooling to rt, the mixture was partitioned between 1M HCl and EA. The aq. layer was extracted with EA and the combined org. layers were sequentially washed with water, NH.sub.4Cl, NaHCO.sub.3, dried over MgSO.sub.4 and concentrated under reduced pressure. The residue was purified by CC (DCM/MeOH/NH.sub.4OH 1000:50:4), affording a pale orange solid (104 mg; 85% yield).

(674) MS (ESI, m/z): 321.5 [M+H.sup.+].

BY.ii. rac-1-amino-9-chloro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(675) Starting from intermediate BY.i (90 mg) and using procedure B, the title compound was obtained as an off-white solid (55 mg, 89% yield).

Preparation BZ: rac-1-amino-9-ethyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

BZ.i. rac-(4-oxo-9-trimethylsilanylethynyl-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-carbamic acid tert-butyl ester

(676) PdCl.sub.2(PPh.sub.3).sub.2 (23 mg) and CuI (7.8 mg) were added to a suspension of intermediate BE.ix (300 mg) in TEA-dioxane (3 mL; 4:1). The reaction mixture was heated to 70° C. and ethynyl-trimethyl-silane (0.14 mL) was added in one portion and the reaction mixture was further heated in a sealed glass vial at 100° C. for 2 days. After cooling to rt, the mixture was partitioned between 1M HCl and DCM. The org. layer was sequentially washed with water, NH.sub.4Cl, and NaHCO.sub.3, dried over MgSO.sub.4 and concentrated under reduced pressure. The residue was purified by CC (DCM/MeOH/NH.sub.4OH 1000:50.4), affording a beige solid (132 mg; 42% yield).

(677) MS (ESI, m/z): 383.4 [M+H.sup.+].

BZ.ii. rac-(9-ethynyl-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-carbamic acid tert-butyl ester

(678) A solution of intermediate BZ.i (115 mg) in THF (2 mL) was treated with TBAF (1M in THF; 0.33 mL) at rt. After 15 min, the mixture was concentrated, water was added and the mixture was extracted with DCM. The org. layer was dried over MgSO.sub.4, filtered and concentrated. The residue was purified by CC (DCM/MeOH/NH.sub.4OH 1000:50:4), affording a yellow solid (82 mg; 88% yield).

(679) MS (ESI, m/z): 311.6 [M+H.sup.+].

BZ.iii. rac-(9-ethyl-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-carbamic acid tert-butyl ester

(680) A solution of intermediate BZ.ii (40 mg) in MeOH (1 mL) was hydrogenated over Pd/C for 2 h. The suspension was filtered using a glass fiber filter. The filter cake was washed with DCM/MeOH and the filtrate was concentrated under reduced pressure, affording a pale yellow solid (37 mg; 91% yield).

(681) MS (ESI, m/z): 315.3 [M+H.sup.+].

BZ.iv. rac-1-amino-9-ethyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(682) Starting from intermediate BZ.iii. (30 mg) and using procedure B, the title compound was obtained as a colourless solid (13 mg, 64% yield).

(683) MS (ESI, m/z): 215.5 [M+H.sup.+].

Preparation CA: rac-1-amino-9-ethynyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(684) Starting from intermediate BZ.ii (40 mg) and using procedure B, the title compound was obtained as a beige solid (20 mg, 74% yield).

(685) MS (ESI, m/z): 211.3 [M+H.sup.+].

Preparation CB: rac-(1R*,2R*)-1-amino-9-fluoro-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylic acid methyl ester

CB.i. (2S*,3R*)-3-tert-butoxycarbonylamino-2-hydroxy-3-(7-fluoro-2-methoxy-quinolin-8-yl)-propionic acid methyl ester

(686) Starting from (E)-3-(7-fluoro-2-methoxy-quinolin-8-yl)-acrylic acid methyl ester (7.07 g; prepared in analogy to the corresponding n-butyl ester described in WO 2008/128953) and proceeding in analogy to the preparation of intermediate BQ.ii, the title compound was obtained as a light yellow semi-solid material (7.621 g; 84% yield).

(687) MS (ESI, m/z): 395.4 [M+H.sup.+].

CB.ii. rac-(1R*,2R*)-1-tert-butoxycarbonylamino-9-fluoro-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylic acid methyl ester

(688) Starting from intermediate CB.i (4.60 g) and using procedure H, the title intermediate was obtained as a beige solid (81 mg; 19% yield).

(689) MS (ESI, m/z): 363.4 [M+H.sup.+].

CB.iii. rac-(1R*,2R*)-1-amino-9-fluoro-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylic acid methyl ester

(690) Starting from intermediate CB.ii. (100 mg) and using procedure B, the title compound was obtained as a colourless solid (58 mg; 80% yield).

(691) .sup.1H NMR (CDCl.sub.3) δ: 7.71 (dd, J=9.4, 0.9 Hz, 1H), 7.49 (m, 1H), 6.92 (m, 1H), 6.63 (d, J=9.4 Hz, 1H), 5.02 (m, 2H), 3.83 (d, J=1.2 Hz, 3H).

Preparation CC: rac-(1R*,2R*)-1-amino-9-fluoro-2-hydroxymethyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

CC.i. rac-((1R*,2R*)-9-fluoro-2-hydroxymethyl-9-fluoro-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-carbamic acid tert-butyl ester

(692) Starting from intermediate CB.ii (200 mg) and using procedure A, the title intermediate was obtained as a colourless solid (112 mg; 61% yield).

(693) MS (ESI, m/z): 335.4 [M+H.sup.+].

CC.ii. rac-(1R*,2R*)-1-amino-9-fluoro-2-hydroxymethyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(694) Starting from intermediate CC.i (104 mg) and using procedure B, the title compound was obtained as a colourless solid (60 mg; 82% yield).

(695) MS (ESI, m/z): 235.1 [M+H.sup.+].

Preparation CD: rac-(1R*,2S*)-1-amino-9-fluoro-2-methyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

CD.i. rac-((1R*,2S*)-9-fluoro-2-methyl-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-carbamic acid tert-butyl ester

(696) Starting from intermediate CC.i (495 mg) and using procedure H, the intermediate mesylate was formed and further reacted after usual work-up. It was dissolved in DME (25 mL) and refluxed in presence of NaI (710 mg). After 1.5 h, the reaction mixture was treated with Bu.sub.3SnH (0.96 mL) and further refluxed for 3 h. The reaction mixture was diluted in ether and stirred in presence of 8% aq. KF for 16 h. The mixture was filtered. The two phases were separated and the aq. layer was extracted with EA. The combined org. layers were washed with water and brine and dried over MgSO.sub.4. The solvents were removed under reduced pressure and the residue was purified by CC (Hept/EA 1:1 to 0:1), affording a colourless solid (374 mg; 79% yield).

(697) MS (ESI, m/z): 319.3 [M+H.sup.+].

CD.ii. rac-(1R*,2S*)-1-amino-9-fluoro-2-methyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(698) Starting from intermediate CD.i (370 mg) and using procedure B, the title compound was obtained as a colourless solid (198 mg; 78% yield).

(699) MS (ESI, m/z): 218.9 [M+H.sup.+].

Preparation CE: rac-(1R*,2R*)-methanesulfonic acid 1-amino-9-fluoro-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-2-ylmethyl ester

CE.i. rac-(1R*,2R*)-methanesulfonic acid 1-tert-butoxycarbonylamino-9-fluoro-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-2-ylmethyl ester

(700) Starting from intermediate CC.i (200 mg) and using procedure H, the title compound was obtained as a yellow foam (285 mg; 100% yield).

(701) MS (ESI, m/z): 413.3 [M+H.sup.+].

CE.ii. rac-(1R*,2R*)-methanesulfonic acid 1-amino-9-fluoro-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-2-ylmethyl ester

(702) Starting from intermediate CE.i (280 mg) and using procedure B, the title compound was obtained as a beige foam (140 mg; 77% yield).

(703) MS (ESI, m/z): 313.5 [M+H.sup.+].

Preparation CF: (S)-1-amino-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(704) Intermediate C was separated by chiral prep. HPLC (Column: Daicel, ChiralPak IA, 20×250 mm; eluent: 5% EtOH in MeCN+0.1% DEA; flow: 16.00 mL/min). The title compound was obtained as the first eluting compound (t.sub.R=7.36 min). The absolute stereochemistry was assigned based on the NMR of the corresponding Mosher amide.

(705) MS (ESI, m/z): 205.2 [M+H.sup.+].

Preparation CG: (R)-1-amino-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(706) Intermediate C was separated by chiral prep. HPLC (Column: Daicel, ChiralPak IA, 20×250 mm; eluent: 5% EtOH in MeCN+0.1% DEA; flow: 16.00 mL/min). The title compound was obtained as the second eluting compound (t.sub.R=8.94 min). The absolute stereochemistry was assigned based on the NMR of the corresponding Mosher amide.

(707) MS (ESI, m/z): 205.2 [M+H.sup.+].

Preparation CH: methanesulfonic acid 2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethyl ester

(708) This intermediate was prepared in analogy to Preparation BX, steps BX.i to BX.iii, using however the (S,S)-(salen)Co.sup.II complex.

(709) The analytical data were identical with those of the compound of Preparation BX.

Preparation CI: (RS)-6-amino-7-fluoro-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

(710) The title compound was prepared as described in Preparation AD, using however NMO and K.sub.2OsO.sub.4 as dihydroxylating agent (Cha, J. K., Chem. Rev. (1995), 95, 1761-1795) in the first step.

(711) The analytical data were identical with those of the compound of Preparation AD.

Example 1: (1RS)-9-fluoro-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(712) Starting from the compounds of Preparations A and H and using procedure C, the title compound was obtained as a pale yellow solid (39 mg; 18% yield).

(713) .sup.1H NMR (DMSO-d.sub.6) δ: 10.71 (s, 1H), 7.89 (d, J=9.4 Hz, 1H), 7.58 (m, 1H), 7.32 (m, 1H), 6.94 (m, 3H), 6.50 (d, J=9.4 Hz, 1H), 4.67 (m, 1H), 4.53 (s, 2H), 4.36 (m, 2H), 4.00 (m, 2H), 3.67 (m, 1H), 3.02 (m, 1H), 2.74 (m, 3H), 2.04 (m, 1H), 1.81 (m, 2H).

(714) MS (ESI, m/z): 479.3 [M+H.sup.+].

Example 2: (1RS)-9-fluoro-1-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(715) Starting from the compounds of Preparations A and I and using procedure C, the title compound was obtained as a pale yellow solid (35 mg; 16% yield).

(716) .sup.1H NMR (DMSO-d.sub.6) δ: 10.71 (s, 1H), 7.88 (d, J=9.4 Hz, 1H), 7.59 (dd, J=8.8, 4.7 Hz, 1H), 7.32 (m, 1H), 6.96 (m, 3H), 6.50 (d, J=9.4 Hz, 1H), 4.68 (m, 1H), 4.53 (s, 2H), 4.32 (m, 2H), 4.00 (m, 2H), 3.65 (m, 1H), 3.02 (m, 1H), 2.74 (m, 3H), 2.04 (m, 1H), 1.83 (m, 2H).

(717) MS (ESI, m/z): 479.3 [M+H.sup.+].

Example 3: (1RS)-9-fluoro-1-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(718) Starting from the compounds of Preparations A and J and using procedure C, the title compound was obtained as an off-white solid (34 mg; 15% yield).

(719) .sup.1H NMR (DMSO-d.sub.6) δ: 10.56 (s, 1H), 7.88 (d, J=9.4 Hz, 1H), 7.59 (m, 1H), 7.32 (m, 2H), 7.01 (m, 2H), 6.50 (dd, J=9.7, 0.9 Hz, 1H), 4.69 (m, 1H), 4.32 (m, 2H), 4.02 (m, 2H), 3.66 (m, 1H), 3.43 (s, 2H), 3.02 (m, 1H), 2.74 (m, 3H), 1.90 (m, 3H).

(720) MS (ESI, m/z): 495.3 [M+H.sup.+].

Example 4: (1RS)-9-fluoro-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(721) Starting from the compounds of Preparations A and K and using procedure D, the title compound was obtained as an off-white solid (79 mg; 35% yield).

(722) .sup.1H NMR (DMSO-d.sub.6) δ: 10.55 (s, 1H), 7.88 (d, J=9.7 Hz, 1H), 7.57 (m, 1H), 7.32 (m, 2H), 7.01 (m, 2H), 6.50 (dd, J=9.4, 0.6 Hz, 1H), 4.69 (m, 1H), 4.34 (m, 2H), 4.03 (m, 2H), 3.66 (m, 1H), 3.42 (s, 2H), 3.02 (s, 1H), 2.72 (m, 3H), 1.99 (m, 1H), 1.84 (m, 2H).

(723) MS (ESI, m/z): 495.3 [M+H.sup.+].

Example 5: (1RS)-9-fluoro-1-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(724) Starting from the compounds of Preparations A and N and using procedure D, the title compound was obtained as a yellow solid (31 mg; 37% yield).

(725) MS (ESI, m/z): 481.1 [M+H.sup.+].

Example 6: (1RS)-9-fluoro-1-({2-[(RS)-3-(3-fluoro-4-methyl-phenyl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-U]quinolin-4-one

(726) Starting from the compounds of Preparations A and S and using procedure C, the title compound was obtained as a yellow solid (94 mg; 47% yield).

(727) MS (ESI, m/z): 440.5 [M+H.sup.+].

Example 7: (1RS)-1-(2-{[(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-ethyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(728) Starting from the compounds of Preparations B and P and using procedure D, the title compound was obtained as a pale yellow solid (45 mg; 28% yield).

(729) MS (ESI, m/z): 466.2 [M+H.sup.+].

Example 8: (1RS)-9-fluoro-1-(2-{[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(730) Starting from the compounds of Preparations B and O and using procedure D, the title compound was obtained as a yellow solid (50 mg; 29% yield).

(731) MS (ESI, m/z): 495.1 [M+H.sup.+].

Example 9: (1RS)-9-fluoro-1-(2-{[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(732) Starting from the compounds of Preparations B and Q and using procedure C, the title compound was obtained as a pale yellow solid (47 mg; 20% yield).

(733) MS (ESI, m/z): 479.2 [M+H.sup.+].

Example 10: (1RS)-9-fluoro-1-(2-{[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(734) Starting from the compounds of Preparations B and N and using procedure D, the title compound was obtained as a pale yellow solid (38 mg; 16% yield).

(735) MS (ESI, m/z): 494.9 [M+H.sup.+].

Example 11: (1RS)-9-fluoro-1-(2-{[(R)-3-(3-fluoro-4-methyl-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(736) Starting from the compounds of Preparations B and R and using procedure D, the title compound was obtained as a yellow solid (29 mg; 19% yield).

(737) MS (ESI, m/z): 440.5 [M+H.sup.+].

Example 12: (1RS)-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(738) Starting from the compounds of Preparations C and T and using procedure E, the title compound was obtained as a colourless solid (42 mg; 45% yield).

(739) .sup.1H NMR (CDCl.sub.3) δ: 7.70 (d, J=9.4 Hz, 1H), 7.47 (m, 1H), 7.32 (m, 1H), 6.92 (m, 2H), 6.76 (m, 1H), 6.62 (d, J=9.4 Hz, 1H), 4.96 (m, 1H), 4.64 (m, 1H), 4.50 (m, 3H), 4.26 (m, 1H), 4.04 (m, 1H), 3.60 (m, 1H), 3.42 (m, 2H), 2.73 (m, 2H), 1.76 (m, 4H).

(740) MS (ESI, m/z): 479.2 [M+H.sup.+].

Example 13: (1RS)-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(741) Starting from the compounds of Preparations C and U and using procedure E, the title compound was obtained as a pale beige solid (48 mg; 50% yield).

(742) .sup.1H NMR (CDCl.sub.3) δ: 7.69 (d, J=9.7 Hz, 1H), 7.47 (dd, J=8.5, 4.7 Hz, 1H), 7.35 (d, J=2.3 Hz, 1H), 7.24 (m, 2H), 6.91 (m, 2H), 6.61 (d, J=9.4 Hz, 1H), 4.95 (dd, J=8.2, 3.2 Hz, 1H), 4.65 (m, 1H), 4.49 (dd, J=13.5, 8.2 Hz, 1H), 4.26 (dd, J=13.2, 3.5 Hz, 1H), 4.06 (m, 1H), 3.60 (m, 1H), 3.36 (s, 2H), 2.73 (m, 2H), 1.77 (m, 5H).

(743) MS (ESI, m/z): 495.0 [M+H.sup.+].

Example 14: (1RS)-9-fluoro-1-{2-[(RS)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(744) Starting from the compounds of Preparations C and M and using procedure C, the title compound was isolated as a pale yellow solid (13 mg; 12% yield).

(745) .sup.1H NMR (CDCl.sub.3) δ: 8.76 (m, 1H), 7.66 (d, J=9.4 Hz, 1H), 7.44 (m, 2H), 7.24 (m, 1H), 6.91 (m, 2H), 6.61 (d, J=9.7 Hz, 1H), 4.96 (m, 1H), 4.80 (m, 1H), 4.50 (m, 1H), 4.28 (m, 1H), 4.08 (m, 1H), 3.68 (m, 1H), 3.38 (s, 2H), 2.94 (m, 2H), 1.97 (m, 3H).

(746) MS (ESI, m/z): 481.1 [M+H.sup.+].

Example 15: (4R)-4-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(747) Starting from the compounds of Preparations V and J and using procedure C, the title compound was obtained as a colourless solid (9 mg; 12% yield).

(748) MS (ESI, m/z): 478.0 [M+H.sup.+].

Example 16: (4RS)-3-fluoro-4-(2-{[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(749) Starting from the compounds of Preparations F and O and using procedure D, the title compound was obtained as a yellow solid (6 mg; 7% yield).

(750) MS (ESI, m/z): 496.3 [M+H.sup.+].

Example 17: (4RS)-3-fluoro-4-(2-{[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(751) Starting from the compounds of Preparations F and N and using procedure D, the title compound was obtained as a yellow solid (8 mg; 9% yield).

(752) MS (ESI, m/z): 496.4 [M+H.sup.+].

Example 18: (4R)-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(753) Starting from the dihydrochloride salt of the compound of Preparation D (112 mg) and the compound of Preparation U (153 mg) and using procedure E, the title compound was obtained as an orange solid (27 mg; 11% yield).

(754) MS (ESI, m/z): 478.1 [M+H.sup.+].

Example 19: (4R)-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(755) Starting from the dihydrochloride salt of the compound of Preparation D (78 mg) and the compound of Preparation T (101 mg) and using procedure E, the title compound was obtained as an orange solid (17 mg; 11% yield).

(756) MS (ESI, m/z): 462.1 [M+H.sup.+].

Example 20: (6RS)-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

(757) Starting from the compounds of Preparations G (93 mg) and U (153 mg) and using procedure E, the title compound was obtained as a yellow solid (210 mg; 88% yield).

(758) MS (ESI, m/z): 478.0 [M+H.sup.+].

Example 21: (6RS)-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

(759) Starting from the compounds of Preparations G and T and using procedure E, the title compound was obtained as a yellow solid (276 mg; 70% yield).

(760) MS (ESI, m/z): 462.1 [M+H.sup.+].

Example 22: (1RS)-9-fluoro-1-(2-{[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one

(761) The compound of Example 8 was hydrogenated according to procedure F, affording a colourless solid (10 mg; 23% yield).

(762) MS (ESI, m/z): 497.3 [M+H.sup.+].

Example 23: (1RS)-9-fluoro-1-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one

23. i. rac-(9-fluoro-4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]quinolin-1-ylmethyl)-carbamic acid tert-butyl ester

(763) A solution of intermediate A.vii of Preparation A (47 mg, 0.15 mmol) in MeOH (5 mL) was hydrogenated over 10% Pd/C (31 mg) for 2 h. The catalyst was filtered off and washed with MeOH. The filtrate was concentrated to afford the title intermediate as a colourless solid (48 mg; 100% yield).

(764) MS (ESI, m/z): 321.3 [M+H.sup.+].

23. ii. rac-1-aminomethyl-9-fluoro-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one

(765) Starting from intermediate 23.i and using procedure B, the title intermediate was obtained as a yellow solid (29 mg; 88% yield).

(766) MS (ESI, m/z): 221.2 [M+H.sup.+].

23. iii. (1RS)-9-fluoro-1-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one

(767) Starting from intermediate 23.ii and the compound of Preparation L and using procedure D, the title compound was obtained as a pale brown solid (8 mg; 14% yield).

(768) MS (ESI, m/z): 497.4 [M+H.sup.+].

Example 24: (1RS)-9-fluoro-1-(2-{[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one

(769) The compound of Example 10 was hydrogenated using procedure F, affording the title compound as an off-white solid (8 mg; 16% yield).

(770) MS (ESI, m/z): 497.2 [M+H.sup.+].

Example 25: (1RS)-9-fluoro-1-(2-{[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one

(771) The compound of Example 9 was hydrogenated using procedure F, affording the title compound as a colourless solid (12 mg; 32% yield).

(772) MS (ESI, m/z): 481.2 [M+H.sup.+].

Example 26: (1RS)-1-(2-{[(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-ethyl)-9-fluoro-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one

(773) The compound of Example 7 was hydrogenated using procedure F, affording the title compound as an off-white solid (21 mg; 52% yield).

(774) MS (ESI, m/z): 468.2 [M+H.sup.+].

Example 27: (1RS)-9-fluoro-1-(2-{[(R)-3-(3-fluoro-4-methyl-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one

(775) The compound of Example 11 was hydrogenated using procedure F, affording the title compound as an off-white solid (17 mg; 74% yield).

(776) MS (ESI, m/z): 442.2 [M+H.sup.+].

Example 28: (4RS)-3-fluoro-4-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(777) Starting from the compounds of Preparations E and L and using procedure D, the title compound was obtained as a yellow solid (7 mg; 18% yield).

(778) MS (ESI, m/z): 496.2 [M+H.sup.+].

Example 29: (1RS)-9-fluoro-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one

(779) The compound of Example 4 was hydrogenated using procedure F, affording the title compound as a colourless solid (17 mg; 39% yield).

(780) MS (ESI, m/z): 497.2 [M+H.sup.+].

Example 30: (1RS)-9-fluoro-1-({[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(781) Starting from the compounds of Preparations A and O and using procedure D, the title compound was obtained as a yellow solid (49 mg; 37% yield).

(782) MS (ESI, m/z): 481.2 [M+H.sup.+].

Example 31: (1RS)-1-({[(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(783) Starting from the compounds of Preparations A and P and using procedure D, the title compound was obtained as a yellow solid (33 mg; 27% yield).

(784) MS (ESI, m/z): 452.2 [M+H.sup.+].

Example 32: (1RS)-9-fluoro-1-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(785) Starting from the compounds of Preparations A and Q and using procedure C, the title compound was obtained as a yellow solid (35 mg; 27% yield).

(786) MS (ESI, m/z): 465.2 [M+H.sup.+].

Example 33: (1RS)-9-fluoro-1-({[(R)-3-(3-fluoro-4-methyl-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(787) Starting from the compounds of Preparations A and R and using procedure D, the title compound was obtained as a yellow solid (17 mg; 15% yield).

(788) MS (ESI, m/z): 426.2 [M+H.sup.+].

Example 34: (RS)-4-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(789) Starting from the compound of Preparations W and AF and using procedure C, the title compound was obtained as a beige solid (13 mg; 8% yield).

(790) MS (ESI, m/z): 478.0 [M+H.sup.+].

Example 35: (RS)-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(791) Starting from the compounds of Preparations X and U and using procedure E, the title compound was obtained as a beige solid (30 mg; 24% yield).

(792) MS (ESI, m/z): 476.9 [M+H.sup.+].

Example 36: (RS)-1-({[(R)-3-(4-ethoxy-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(793) Starting from the compound of Preparation A and (5S)-3-(4-ethoxyphenyl)-5-[[(methylsulfonyl)oxy]methyl]-2-oxazolidinone (prepared according to WO 2008/126034) and using procedure C, the title compound was obtained as a yellow solid (44 mg; 27% yield).

(794) MS (ESI, m/z): 472.3 [M+H.sup.+].

Example 37: (RS)-9-fluoro-1-({[(R)-2-oxo-3-(4-propyl-phenyl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(795) Starting from the compounds of Preparations A and AG and using procedure C, the title compound was obtained as a yellow solid (46 mg; 29% yield).

(796) MS (ESI, m/z): 436.1 [M+H.sup.+].

Example 38: (RS)-1-({[(R)-3-(4-butyl-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(797) Starting from the compounds of Preparations A and AH and using procedure C, the title compound was obtained as a yellow solid (36 mg; 22% yield).

(798) MS (ESI, m/z): 450.1 [M+H.sup.+].

Example 39: (S)-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(799) Starting from the compounds of Preparations Y and U and using procedure E, the title compound was obtained as a beige solid (90 mg; 23% yield).

(800) MS (ESI, m/z): 477.9 [M+H.sup.+].

Example 40: (S)-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(801) Starting from the compounds of Preparations Y and T and using procedure E, the title compound was obtained as a beige foam (55 mg; 15% yield).

(802) MS (ESI, m/z): 461.9 [M+H.sup.+].

Example 41: (S)-4-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(803) Starting from the compounds of Preparations Y and AI and using procedure C, the title compound was obtained as a yellow solid (10 mg; 2% yield).

(804) MS (ESI, m/z): 464.1 [M+H.sup.+].

Example 42: (RS)-1-({2-[(RS)-3-(2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(805) Starting from the compounds of Preparations A and AJ and using procedure C, the title compound was obtained as a yellow solid (48 mg; 34% yield).

(806) MS (ESI, m/z): 467.1 [M+H.sup.+].

Example 43: (RS)-1-({2-[(RS)-3-(2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-6-yl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(807) Starting from the compounds of Preparations A and AK and using procedure C, the title compound was obtained as a yellow foam (42 mg; 30% yield).

(808) MS (ESI, m/z): 467.1 [M+H.sup.+].

Example 44: (RS)-1-({2-[(R)-3-(4-ethoxy-phenyl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(809) Starting from the compounds of Preparations A and AL and using procedure C, the title compound was obtained as a yellow foam (20 mg; 14% yield).

(810) .sup.1H NMR (CDCl.sub.3) δ: 7.65 (dd, J=9.4, 1.5 Hz, 1H), 7.38 (m, 3H), 6.87 (m, 3H), 6.60 (d, J=9.7 Hz, 1H), 4.70 (m, 1H), 4.44 (m, 2H), 4.01 (m, 4H), 3.61 (td, J=9.1, 7.3 Hz, 1H), 3.14 (m, 1H), 2.90 (m, 3H), 1.92 (m, 2H), 1.39 (t, J=6.7 Hz, 3H).

Example 45: (RS)-9-fluoro-1-({2-[(R)-2-oxo-3-(4-propyl-phenyl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(811) Starting from the compounds of Preparations A and AM and using procedure C, the title compound was obtained as a yellow foam (24 mg; 17% yield).

(812) .sup.1H NMR (CDCl.sub.3) δ: 7.65 (dd, J=9.7, 1.5 Hz, 1H), 7.39 (m, 3H), 7.16 (d, J=8.5 Hz, 2H), 6.87 (td, J=9.1, 1.8 Hz, 1H), 6.60 (d, J=9.4 Hz, 1H), 4.72 (m, 1H), 4.44 (m, 2H), 4.02 (m, 2H), 3.64 (m, 1H), 3.14 (m, 1H), 2.90 (m, 3H), 2.55 (m, 2H), 1.91 (m, 2H), 1.61 (m, 2H), 0.92 (t, J=7.3 Hz, 3H).

(813) MS (ESI, m/z): 450.1 [M+H.sup.+].

Example 46: (RS)-1-({2-[(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(814) Starting from the compounds of Preparations A and AN and using procedure C, the title compound was obtained as an off-white solid (32 mg; 21% yield).

(815) .sup.1H NMR (CDCl.sub.3) δ: 7.64 (dd, J=9.4, 1.2 Hz, 1H), 7.38 (dd, J=8.8, 4.7 Hz, 1H), 7.03 (t, J=2.3 Hz, 1H), 6.89 (m, 3H), 6.58 (d, J=9.4 Hz, 1H), 4.68 (m, 1H), 4.48 (m, 1H), 4.36 (m, 1H), 4.22 (m, 4H), 3.97 (m, 2H), 3.56 (m, 1H), 3.12 (m, 1H), 2.88 (m, 3H), 1.90 (m, 2H).

(816) MS (ESI, m/z): 466.0 [M+H.sup.+].

Example 47: (RS)-9-fluoro-1-({2-[(RS)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(817) Starting from the compounds of Preparations A and AO and using procedure C, the intermediate (RS)-9-fluoro-1-[(2-{3-[(RS)-4-(4-methoxy-benzyl)-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl]-2-oxo-oxazolidin-5-yl}-ethylamino)-methyl]-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one was obtained as a yellowish foam (148 mg, 36% yield). Said intermediate was further treated with TFA (4 mL) at reflux for 3 days. The solvent was removed under reduced pressure and the residue was partitioned between DCM and aq. NH.sub.4OH. The org. phase was washed with water and brine and dried over MgSO.sub.4. The residue was purified by CC (EA/MeOH 9:1 containing 1% NH.sub.4OH), affording, after trituration in ether/MeOH, a beige solid (55 mg; 17% yield).

(818) MS (ESI, m/z): 480.0 [M+H.sup.+].

Example 48: (S)-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

(819) Starting from the compounds of Preparations Z and U and using procedure E, the title compound was obtained as a beige solid (135 mg; 53% yield).

(820) .sup.1H NMR (DMSO d6) δ: 10.54 (s, 1H), 8.17 (s, 1H), 7.70 (d, J=7.9 Hz, 1H), 7.60 (d, J=7.3 Hz, 1H), 7.31 (m, 3H), 7.06 (dd, J=8.5, 2.3 Hz, 1H), 4.70 (m, 2H), 4.44 (m, 1H), 4.07 (m, 2H), 3.62 (dd, J=8.8, 7.3 Hz, 1H), 3.41 (s, 2H), 2.63 (m, 2H), 1.76 (m, 2H), 1.53 (m, 2H).

Examples 49 and 50

(S)-9-fluoro-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one and (R)-9-fluoro-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(821) Starting from the compounds of Preparations A and AI and using procedure C, the title compounds were obtained as a light yellow solid (466 mg, 26%, mixture of diastereoisomers; MS (ESI, m/z): 495.1 [M+H.sup.+]). This mixture (75 mg) was separated on a chiral HPLC column (ChiralPak IA, 4.6×250 mm, 5 μm; eluents: MeCN and EtOH containing 0.1% of DEA) affording the corresponding diastereoisomers:

(822) First eluting compound (27 mg): .sup.1H NMR (CDCl.sub.3) δ: 7.69 (d, J=9.4 Hz, 1H), 7.41 (dd, J=8.5, 4.4 Hz, 1H), 7.23 (m, 1H), 7.12 (m, 2H), 6.89 (t, J=9.1 Hz, 1H), 6.62 (d, J=9.7 Hz, 1H), 4.71 (m, 1H), 4.45 (m, 2H), 4.03 (m, 2H), 3.62 (m, 2H), 3.34 (s, 2H), 2.95 (m, 3H), 2.00 (m, 1H), 1.78 (m, 1H).

(823) Second eluting compound (20 mg): .sup.1H NMR (CDCl.sub.3) δ: 7.69 (d, J=9.4 Hz, 1H), 7.41 (dd, J=8.8, 4.4 Hz, 1H), 7.22 (m, 2H), 7.08 (dd, J=8.5, 2.3 Hz, 1H), 6.89 (t, J=9.1 Hz, 1H), 6.60 (d, J=9.4 Hz, 1H), 4.62 (m, 1H), 4.48 (m, 1H), 4.35 (m, 1H), 3.96 (m, 2H), 3.71 (m, 1H), 3.34 (s, 2H), 3.10 (dd, J=12.0, 4.4 Hz, 1H), 2.88 (m, 3H), 1.91 (m, 2H).

Example 51: (RS)-9-fluoro-1-({3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(824) Starting from the compounds of Preparations A and U and using procedure E, the title compound was obtained as a light yellow foam (69 mg; 59% yield).

(825) MS (ESI, m/z): 509.2 [M+H.sup.+].

Example 52: (RS)-9-fluoro-1-({3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(826) Starting from the compounds of Preparations A and T and using procedure E, the title compound was obtained as a light yellow foam (60 mg; 53% yield).

(827) MS (ESI, m/z): 493.2 [M+H.sup.+].

Example 53: (RS)-1-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-U]quinolin-4-one

(828) Starting from the compounds of Preparations AB and AF and using procedure C, the title compound was obtained as a light yellow foam (10 mg; 8% yield).

(829) MS (ESI, m/z): 476.9 [M+H.sup.+].

Example 54: (S)-6-{2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

(830) Starting from the compounds of Preparations Z and J and using procedure C, the title compound was obtained as an orange solid (30 mg, 14% yield).

(831) MS (ESI, m/z): 464.1 [M+H.sup.+].

Example 55: (S)-6-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

(832) Starting from the compounds of Preparation Z and intermediate K.iv and using procedure C, the title compound was obtained as an orange solid (50 mg; 20% yield).

(833) MS (ESI, m/z): 464.3 [M+H.sup.+].

Example 56: (RS)-6-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

(834) Starting from the compounds of Preparations AC and AI and using procedure C, the title compound was obtained as a yellow foam (98 mg; 28% yield).

(835) MS (ESI, m/z): 477.9 [M+H.sup.+].

Example 57: (S)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

(836) Starting from the compounds of Preparations AD and T and using procedure E, the title compound was obtained as a colourless solid (70 mg; 29% yield).

(837) MS (ESI, m/z): 480.1 [M+H.sup.+].

Example 58: (S)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

(838) Starting from the compounds of Preparations AD and U and using procedure E, the title compound was obtained as a colourless solid (85 mg; 34% yield).

(839) MS (ESI, m/z): 469.1 [M+H.sup.+].

Example 59: (RS)-9-fluoro-1-{2-[(R)-2-oxo-3-(4-propyl-phenyl)-oxazolidin-5-yl]-ethylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(840) Starting from the compounds of Preparations C and AM and using procedure C, the title compound was obtained as a yellow solid (46 mg; 31% yield).

(841) .sup.1H NMR (CDCl.sub.3) δ: 7.68 (dd, J=9.4, 0.9 Hz, 1H), 7.45 (m, 3H), 7.17 (d, J=8.2 Hz, 2H), 6.92 (t, J=8.8 Hz, 1H), 6.61 (d, J=9.4 Hz, 1H), 4.99 (m, 1H), 4.78 (m, 1H), 4.52 (m, 1H), 4.31 (dd, J=13.2, 3.2 Hz, 1H), 4.10 (t, J=8.5 Hz, 1H), 3.69 (m, 1H), 2.95 (m, 2H), 2.56 (m, 2H), 2.02 (m, 2H), 1.62 (m, 2H), 0.92 (t, J=7.3 Hz, 3H).

(842) MS (ESI, m/z): 436.2 [M+H.sup.+].

Example 60: (RS)-1-({2-[(S)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(843) Starting from the compounds of Preparations A and AQ and using procedure C, the title compound was obtained as a yellow foam (29 mg; 34% yield).

(844) .sup.1H NMR (CDCl.sub.3) δ: 7.65 (dd, J=9.7, 0.9 Hz, 1H), 7.39 (dd, J=8.8, 4.7 Hz, 1H), 7.02 (t, J=2.1 Hz, 1H), 6.87 (m, 3H), 6.58 (d, J=9.4 Hz, 1H), 4.70 (m, 1H), 4.44 (m, 2H), 4.22 (m, 4H), 3.98 (m, 2H), 3.58 (m, 2H), 3.15 (m, 1H), 2.91 (m, 3H), 1.92 (m, 2H).

(845) MS (ESI, m/z): 466.2 [M+H.sup.+].

Example 61: (RS)-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-U]quinolin-4-one

(846) Starting from the compounds of Preparations AE and AI and using procedure C, the title compound was obtained as a beige solid (110 mg; 46% yield).

(847) .sup.1H NMR (DMSO d6) δ: 10.58 (s, 1H), 7.90 (d, J=9.7 Hz, 1H), 7.54 (m, 2H), 7.32 (m, 2H), 7.18 (t, J=7.9 Hz, 1H), 7.08 (m, 1H), 6.55 (d, J=9.7 Hz, 1H), 4.81 (m, 1H), 4.39 (m, 2H), 4.08 (m, 3H), 3.72 (m, 1H), 3.42 (s, 3H), 3.05 (m, 4H), 2.12 (m, 2H).

(848) MS (ESI, m/z): 476.8 [M+H.sup.+].

Example 62: (RS)-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-U]quinolin-4-one

(849) Starting from the compounds of Preparations AE and H and using procedure C, the title compound was obtained as a beige solid (90 mg; 39% yield).

(850) MS (ESI, m/z): 460.9 [M+H.sup.+].

Example 63: (RS)-1-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(851) Starting from the compounds of Preparations AE and N and using procedure D, the title compound was obtained as a beige solid (44 mg; 19% yield).

(852) MS (ESI, m/z): 462.9 [M+H.sup.+].

Example 64: (R)-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

(853) Starting from the compounds of Preparations AA and U and using procedure E, the title compound was obtained as an orange solid (100 mg; 42% yield).

(854) MS (ESI, m/z): 477.8 [M+H.sup.+].

Example 65: (R)-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

(855) Starting from the compounds of Preparations AA and T and using procedure E, the title compound was obtained as an orange solid (140 mg; 61% yield).

(856) MS (ESI, m/z): 461.9 [M+H.sup.+].

Example 66: (S)-7-fluoro-6-((2-hydroxy-ethyl)-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-amino)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

(857) Starting from the compound of Example 58 and (tert-butyldimethylsilyloxy)-acetaldehyde and using procedure E, followed by treatment of the intermediate thus obtained with aq. TFA (50%; 2 mL), the title compound was obtained as a colourless foam (45 mg; 40% yield).

(858) MS (ESI, m/z): 539.9 [M+H.sup.+].

Example 67: (S)-7-fluoro-6-((2-hydroxy-ethyl)-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propyl}-amino)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

(859) Starting from the compound of Example 57 and (tert-butyldimethylsilyloxy)-acetaldehyde and using procedure E, followed by treatment of the intermediate thus obtained with aq. TFA (50%; 2 mL), the title compound was obtained as a colourless foam (80 mg; 45% yield).

(860) MS (ESI, m/z): 523.9 [M+H.sup.+].

Example 68: (RS)-9-fluoro-1-(2-{(3-hydroxy-propyl)-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

68. i. (RS)-1-(2-{[3-(tert-butyl-dimethyl-silanyloxy)-propyl]-[2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(861) Starting from the compound of Example 10 and 3-(tert-butyldimethylsilyloxy)-propionaldehyde and using procedure E, the title compound was obtained as a colourless solid (101 mg; 75% yield).

(862) MS (ESI, m/z): 667.4 [M+H.sup.+].

68. ii. (RS)-9-fluoro-1-(2-{(3-hydroxy-propyl)-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(863) Starting from intermediate 68.i and using procedure J, the title compound was obtained as an off-white solid (70 mg; 87% yield).

(864) MS (ESI, m/z): 553.2 [M+H.sup.+].

Example 69: (RS)-9-fluoro-1-(2-{(2-hydroxy-ethyl)-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

69. i. (RS)-1-(2-{[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-[2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(865) Starting from the compound of Example 10 and tert-butyldimethylsilyloxy-acetaldehyde and using procedure E, the title compound was obtained as a colourless solid (100 mg; 76% yield).

(866) MS (ESI, m/z): 653.4 [M+H.sup.+].

69. ii. (RS)-9-fluoro-1-(2-{(2-hydroxy-ethyl)-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(867) Starting from intermediate 69.i and using procedure J, the title compound was obtained as an off-white solid (54 mg; 69% yield).

(868) MS (ESI, m/z): 539.2 [M+H.sup.+].

Example 70: (RS)-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(869) Starting from the compounds of Preparations C and AR and using procedure E, the title compound was obtained as a colourless solid (175 mg; 73% yield).

(870) MS (ESI, m/z): 480.0 [M+H.sup.+].

Example 71: (S)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

(871) Starting from the compounds of Preparations AD and AR and using procedure E, the title compound was obtained as a colourless solid (87 mg; 36% yield).

(872) MS (ESI, m/z): 481.1 [M+H.sup.+].

Example 72: (S)-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(873) Starting from the compounds of Preparations AS and U and using procedure E, the title compound was obtained as a colourless solid (223 mg; 72% yield).

(874) MS (ESI, m/z): 477.2 [M+H.sup.+].

Example 73: (S)-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(875) Starting from the compounds of Preparations AS and T and using procedure E, the title compound was obtained as a colourless solid (259 mg; 87% yield).

(876) MS (ESI, m/z): 461.2 [M+H.sup.+].

Example 74: (S)-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(877) Starting from the compounds of Preparations AS and AR and using procedure E, the title compound was obtained as a colourless solid (190 mg; 83% yield).

(878) MS (ESI, m/z): 462.2 [M+H.sup.+].

Example 75: (R)-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

(879) Starting from the compounds of Preparations AA and AR and using procedure E, the title compound was obtained as an orange solid (54 mg; 23% yield).

(880) MS (ESI, m/z): 463.0 [M+H.sup.+].

Example 76: (S)-4-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(881) Starting from the compounds of Preparations AT and J and using procedure C, the title compound was obtained as a pale yellow solid (24 mg; 7% yield).

(882) .sup.1H NMR (DMSO-d.sub.6) δ: 10.54 (s, 1H), 8.44 (d, J=4.4 Hz, 1H), 7.94 (d, J=9.7 Hz, 1H), 7.52 (dd, J=4.4, 0.6 Hz, 1H), 7.31 (m, 2H), 7.04 (m, 1H), 6.77 (d, J=9.7 Hz, 1H), 4.74 (m, 1H), 4.38 (m, 1H), 4.10 (m, 2H), 3.90 (m, 1H), 3.66 (m, 1H), 3.42 (s, 2H), 2.90 (m, 2H), 2.69 (m, 2H), 1.86 (m, 2H).

(883) MS (ESI, m/z): 478.2 [M+H.sup.+].

Example 77: (S)-4-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(884) Starting from the compounds of Preparations AT and K and using procedure D, the title compound was obtained as a beige solid (25 mg; 7% yield).

(885) MS (ESI, m/z): 478.2 [M+H.sup.+].

Example 78: (R)-4-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(886) Starting from the compounds of Preparations V and K and using procedure D, the title compound was obtained as a pale yellow solid (150 mg, 42% yield).

(887) MS (ESI, m/z): 478.2 [M+H.sup.+].

Example 79: (S)-7-fluoro-6-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

(888) Starting from the compounds of Preparations AD and AU and using procedure E, the title compound was obtained as a pale yellow foam (195 mg; 79% yield).

(889) .sup.1H NMR (DMSO-d.sub.6) δ: 10.53 (s, 1H), 8.13 (m, 1H), 7.76 (dd, J=8.8, 4.1 Hz, 1H), 7.34 (d, J=2.3 Hz, 1H), 7.29 (d, J=8.5 Hz, 1H), 7.10 (m, 2H), 4.87 (m, 1H), 4.65 (m, 1H), 4.44 (dd, J=12.9, 8.2 Hz, 1H), 4.08 (m, 2H), 3.62 (dd, J=8.8, 7.0 Hz, 1H), 3.41 (s, 2H), 2.60 (m, 2H), 1.74 (m, 2H), 1.74 (m, 2H).

Example 80: (S)-7-fluoro-6-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

(890) Starting from the compounds of Preparations AD and AV and using procedure E, the title compound was obtained as a pale yellow solid (215 mg; 90% yield).

(891) .sup.1H NMR (DMSO-d.sub.6) δ: 10.69 (s, 1H), 8.13 (s, 1H), 7.76 (dd, J=8.8, 4.4 Hz, 1H), 7.31 (d, J=2.3 Hz, 1H), 7.13 (t, J=9.1 Hz, 1H), 6.91 (m, 2H), 4.51 (s, 2H), 4.43 (m, 1H), 4.07 (m, 2H), 2.60 (m, 2H), 1.75 (m, 2H), 1.55 (m, 2H).

Example 81: (RS)-1-({[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(892) Starting from the compounds of Preparations AE and O and using procedure D, the title compound was obtained as a pale yellow solid (42 mg; 18% yield).

(893) MS (ESI, m/z): 463.2 [M+H.sup.+].

Example 82: (RS)-1-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(894) Starting from the compounds of Preparations AE and Q and using procedure C, the title compound was obtained as a beige solid (65 mg; 29% yield).

(895) MS (ESI, m/z): 447.3 [M+H*].

Example 83: (RS)-1-({3-[(RS)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(896) Starting from the compounds of Preparations AE and AW and using procedure C, the title compound was obtained as a beige solid (40 mg; 16% yield).

(897) MS (ESI, m/z): 490.9 [M+H.sup.+].

Example 84: (RS)-3-fluoro-4-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(898) Starting from the compound of Preparation AX and intermediate K.iv and using procedure C, the title compound was obtained as a light brown solid (4 mg; 3% yield).

(899) MS (ESI, m/z): 482.2 [M+H.sup.+].

Example 85: (S)-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(900) Starting from the compounds of Preparations AS and AU and using procedure E, the title compound was obtained as an off-white solid (182 mg; 77% yield).

(901) MS (ESI, m/z): 476.9 [M+H.sup.+].

Example 86: (S)-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(902) Starting from the compounds of Preparations AS and AV and using procedure E, the title compound was obtained as an off-white solid (167 mg; 72% yield).

(903) MS (ESI, m/z): 460.9 [M+H.sup.+].

Example 87: (S)-1-{2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(904) Starting from the compounds of Preparations AS and J and using procedure C, the title compound was obtained as a light brown solid (82 mg; 27% yield).

(905) MS (ESI, m/z): 462.9 [M+H.sup.+].

Example 88: (S)-1-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(906) Starting from the compound of Preparation AS and intermediate K.iv and using procedure C, the title compound was obtained as a light brown solid (99 mg; 33% yield).

(907) MS (ESI, m/z): 463.0 [M+H.sup.+].

Example 89: (S)-1-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(908) Starting from the compounds of Preparations AS and AY and using procedure C, the title compound was obtained as a light brown solid (76 mg; 26% yield).

(909) MS (ESI, m/z): 447.0 [M+H.sup.+].

Example 90: (RS)-9-fluoro-1-[((3-hydroxy-propyl)-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethyl}-amino)-methyl]-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

90.i. (RS)-1-[([3-(tert-butyl-dimethyl-silanyloxy)-propyl]-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethyl}-amino)-methyl]-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(910) Starting from the compound of Example 4 and 3-(tert-butyldimethylsilyloxy)-propionaldehyde and using procedure E, the title compound was obtained as a yellow foam (82 mg; 87% yield).

(911) MS (ESI, m/z): 667.4 [M+H.sup.+].

90. ii. (RS)-9-fluoro-1-[((3-hydroxy-propyl)-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethyl}-amino)-methyl]-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(912) Starting from intermediate 90.i and using procedure J, the title compound was obtained as a light yellow foam (46 mg; 68% yield).

(913) MS (ESI, m/z): 553.2 [M+H.sup.+].

Example 91: (RS)-9-fluoro-1-[((2-hydroxy-ethyl)-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethyl}-amino)-methyl]-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

91.i. (RS)-1-[([2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethyl}-amino)-methyl]-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(914) Starting from the compound of Example 4 and tert-butyldimethylsilyloxy-acetaldehyde and using procedure E, the title compound was obtained as a yellow foam (55 mg; 59% yield).

(915) MS (ESI, m/z): 653.4 [M+H.sup.+].

91. ii. (RS)-9-fluoro-1-[((2-hydroxy-ethyl)-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethyl}-amino)-methyl]-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(916) Starting from intermediate 91.i and using procedure J, the title compound was obtained as an off-white foam (25 mg; 55% yield).

(917) MS (ESI, m/z): 539.2 [M+H.sup.+].

Example 92: (RS)-9-fluoro-1-((3-hydroxy-propyl)-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-amino)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

92.i. (RS)-1-([3-(tert-butyl-dimethyl-silanyloxy)-propyl]-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-amino)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(918) Starting from the compound of Example 13 and 3-(tert-butyldimethylsilyloxy)-propionaldehyde and using procedure E, the title compound was obtained as a yellow foam (62 mg; 46% yield).

(919) MS (ESI, m/z): 667.4 [M+H.sup.+].

92. ii. (RS)-9-fluoro-1-((3-hydroxy-propyl)-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-amino)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(920) Starting from intermediate 92.i and using procedure J, the title compound was obtained as an off-white foam (20 mg; 39% yield).

(921) MS (ESI, m/z): 553.2 [M+H.sup.+].

Example 93: (RS)-9-fluoro-1-((2-hydroxy-ethyl)-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-amino)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

93.i. (RS)-1-([2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-amino)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(922) Starting from the compound of Example 13 and tert-butyldimethylsilyloxy-acetaldehyde and using procedure E, the title compound was obtained as a yellow foam (57 mg; 43% yield).

(923) MS (ESI, m/z): 653.4 [M+H.sup.+].

93. ii. (RS)-9-fluoro-1-((2-hydroxy-ethyl)-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-amino)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(924) Starting from intermediate 93.i and using procedure J, the title compound was obtained as a yellowish foam (15 mg; 32% yield).

(925) MS (ESI, m/z): 539.2 [M+H.sup.+].

Example 94: (RS)-3-fluoro-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(926) Starting from the compounds of Preparations AX and U and using procedure E, the title compound was obtained as a light yellow solid (44 mg; 36% yield).

(927) MS (ESI, m/z): 496.2 [M+H.sup.+].

Example 95: (RS)-3-fluoro-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(928) Starting from the compounds of Preparations AX and T and using procedure E, the title compound was obtained as a light yellow foam (43 mg; 37% yield).

(929) MS (ESI, m/z): 480.2 [M+H.sup.+].

Example 96: (RS)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(930) Starting from the compounds of Preparations AX and AU and using procedure E, the title compound was obtained as an off-white foam (53 mg; 44% yield).

(931) MS (ESI, m/z): 496.2 [M+H.sup.+].

Example 97: (RS)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(932) Starting from the compounds of Preparations AX and AV and using procedure E, the title compound was obtained as a light yellow foam (44 mg; 38% yield).

(933) MS (ESI, m/z): 480.2 [M+H.sup.+].

Example 98: (RS)-3-fluoro-4-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(934) Starting from the compounds of Preparations E and S and using procedure C, the title compound was obtained as a yellow foam (12 mg; 6% yield).

(935) MS (ESI, m/z): 466.2 [M+H.sup.+].

Example 99: (RS)-3-fluoro-4-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(936) Starting from the compounds of Preparations E and AI and using procedure C, the title compound was obtained as a yellow solid (48 mg; 21% yield).

(937) MS (ESI, m/z): 496.2 [M+H.sup.+].

Example 100: (RS)-3-fluoro-4-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(938) Starting from the compounds of Preparations E and N and using procedure D, the title compound was obtained as a yellow foam (27 mg; 12% yield).

(939) MS (ESI, m/z): 482.2 [M+H.sup.+].

Example 101: (RS)-3-fluoro-4-({[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(940) Starting from the compounds of Preparations E and O and using procedure D, the title compound was obtained as a yellow foam (19 mg; 9% yield).

(941) MS (ESI, m/z): 482.2 [M+H.sup.+].

Example 102: (RS)-3-fluoro-4-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(942) Starting from the compounds of Preparations E and H and using procedure C, the title compound was obtained as a yellow foam (15 mg; 7% yield).

(943) MS (ESI, m/z): 480.2 [M+H.sup.+].

Example 103: (RS)-3-fluoro-4-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(944) Starting from the compounds of Preparations E and I and using procedure C, the title compound was obtained as a yellow solid (16 mg; 11% yield).

(945) MS (ESI, m/z): 480.2 [M+H.sup.+].

Example 104: (R)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

(946) Starting from the compounds of Preparations AZ and T and using procedure E, the title compound was obtained as a beige solid (97 mg; 40% yield).

(947) MS (ESI, m/z): 480.2 [M+H.sup.+].

Example 105: (R)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

(948) Starting from the compounds of Preparations AZ and U and using procedure E, the title compound was obtained as a beige solid (81 mg; 32% yield).

(949) MS (ESI, m/z): 496.2 [M+H.sup.+].

Example 106: (RS)-6-({[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

(950) Starting from the compounds of Preparations AC and O and using procedure D, the title compound was obtained as a beige solid (158 mg; 31% yield).

(951) MS (ESI, m/z): 464.2 [M+H.sup.+].

Example 107: (RS)-1-{2-[(S)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-yl]-ethylamino}-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(952) Starting from the compounds of Preparations C and AQ and using procedure C, the title compound was obtained as a light brown solid (20 mg; 23% yield).

(953) MS (ESI, m/z): 452.2 [M+H.sup.+].

Example 108: (RS)—N—((S)-9-fluoro-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-3-hydroxy-3-[(RS)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propionamide

108.i. (RS)-3-(tert-butyl-dimethyl-silanyloxy)-(3RS)-[2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propionic acid

(954) Starting from a solution of intermediate BA.iii (400 mg; see Preparation B) in DCM and treating with TFA, the title intermediate was obtained, after aqueous workup and trituration with ether, as a colourless solid (0.2 g, 56% yield).

(955) MS (ESI, m/z): 453.0 [M+H.sup.+].

108. ii. (RS)—N—((S)-9-fluoro-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-3-hydroxy-3-[(RS)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propionamide

(956) A propylphosphonic anhydride solution (50% in EA, 0.31 ml) was added dropwise to a solution of the compound of Preparation C (0.1 g), intermediate 108.i (0.22 g) and DIPEA (0.26 mL) in DMF (4 mL). The mixture was stirred at rt for 1 h and partitioned between water and EA. The org. phase was washed with dilute HCl and brine, dried over MgSO.sub.4 and concentrated. Purification of the crude using CC (EA/MeOH 19:1) gave a mixture of diastereomeric compounds (ratio and relative stereochemistry was not elucidated) as a colourless solid (245 mg). This intermediate was treated with HCl in MeOH (1.25M), stirred at rt for 1 h, concentrated in vacuo, partitioned between EA and a bicarbonate solution. The product precipitated out of this mixture, was filtered off and dried under HV to give the title compound as a colourless solid (20 mg, mixture of diastereomers).

(957) MS (ESI, m/z): 525.1 [M+H.sup.+].

Example 109: (R)-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(958) Starting from the compounds of Preparations BC and U and using procedure E, the title compound was obtained as a colourless solid (96 mg; 67% yield).

(959) MS (ESI, m/z): 477.2 [M+H.sup.+].

Example 110: (RS)-6-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

(960) Starting from the compounds of Preparations AC and N and using procedure D, the title compound was obtained as a colourless solid (15 mg; 3% yield).

(961) MS (ESI, m/z): 464.2 [M+H.sup.+].

Example 111: (R)-7-fluoro-2-methoxy-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

(962) Starting from the compounds of Preparations BB and T and using procedure E, the title compound was obtained as a colourless solid (100 mg; 39% yield).

(963) MS (ESI, m/z): 510.2 [M+H.sup.+].

Example 112: (R)-7-fluoro-2-methoxy-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

(964) Starting from the compounds of Preparations BB and U and using procedure E, the title compound was obtained as a colourless solid (75 mg; 28% yield).

(965) MS (ESI, m/z): 526.2 [M+H.sup.+].

Example 113: (1RS)-9-fluoro-1-{(3RS)-3-hydroxy-3-[(5RS)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

113.i. 3-(tert-butyl-dimethyl-silanyloxy)-3-[2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propionaldehyde (mixture of diastereomers)

(966) To a solution of the compound of Preparation BA (0.2 g) and DIPEA (0.23 mL) in DCM (5 mL) at rt was added dropwise a solution of SO.sub.3.Pyr complex (0.145 g) in DMSO (0.5 mL) over 2 min. The mixture was stirred at rt for 1.5 h and partitioned between water and DCM. The org. phase was washed several times with water, dried over MgSO.sub.4 and concentrated. The crude product was used as such in the next step (yield assumed to be quantitative).

113. ii. (1RS)-9-fluoro-1-{(3RS)-3-hydroxy-3-[(5RS)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(967) Starting from the compound of Preparation C and intermediate 113.i and using procedure E followed by TBDMS cleavage using procedure J, the title compound was obtained as a yellowish solid (21 mg; 9% yield).

(968) MS (ESI, m/z): 510.6 [M+H.sup.+].

Example 114: (S)-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2,5,6-tetrahydro-pyrrolo[1,2,3-de]quinoxalin-3-one

(969) A solution of the compound of Example 48 (33 mg) in MeOH/DCE (5 mL; 4:1) was treated with NaBH.sub.4 (3 mg) for 30 min then quenched with 1M HCl (1 mL) and partitioned between DCM and an aq. NH.sub.4OH solution. The org. layer was washed with water and brine, dried over MgSO.sub.4 and purified by CC (EA/MeOH 19:1 to 9:1 containing 1% NH.sub.4OH) affording a colourless solid (26 mg; 78% yield).

(970) MS (ESI, m/z): 480.4 [M+H.sup.+].

Example 115: (RS)-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

(971) Starting from the compounds of Preparations G and BK and using procedure E, the title compound was obtained as an orange solid (95 mg, 40% yield).

(972) .sup.1H NMR (DMSO-d.sub.6) δ: 10.82 (s, 1H), 8.17 (s, 1H), 7.77 (m, 1H), 7.68 (m, 2H), 7.60 (d, J=7.3 Hz, 1H), 7.31 (dd, J=7.9, 7.3 Hz, 1H), 4.71 (m, 2H), 4.44 (m, 1H), 4.19 (m, 1H), 4.05 (dd, J=12.9, 3.8 Hz, 1H), 3.69 (dd, J=10.3, 7.0 Hz, 1H), 3.51 (s, 2H), 2.64 (m, 2H), 1.76 (m, 2H), 1.50 (m, 2H).

(973) MS (ESI, m/z): 479.4 [M+H.sup.+].

Example 116: (RS)-9-bromo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(974) Starting from the compounds of Preparations BE and U and using procedure E, the title compound was obtained as a colourless solid (10 mg, 9% yield).

(975) MS (ESI, m/z): 555.2 [M+H.sup.+].

Example 117: (RS)-4-oxo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-9-carbonitrile

(976) Starting from the compounds of Preparations BV and U and using procedure E, the title compound was obtained as a colourless solid (14 mg, 21% yield).

(977) MS (ESI, m/z): 502.5 [M+H.sup.+]

Example 118: (RS)-4-oxo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-9-carbonitrile

(978) Starting from the compounds of Preparations BV and BK and using procedure E, the title compound was obtained as a colourless solid (15 mg, 22% yield).

(979) .sup.1H NMR (CDCl.sub.3) δ: 7.83 (dd, J=8.5, 1.2 Hz, 1H), 7.75 (d, J=9.4 Hz, 1H), 7.58 (m, 2H), 7.41 (d, J=7.9 Hz, 1H), 6.81 (d, J=9.4 Hz, 1H), 5.02 (m, 1H), 4.69 (m, 1H), 4.53 (m, 1H), 4.28 (m, 2H), 3.76 (dd, J=10.5, 7.3 Hz, 1H), 3.43 (s, 2H), 2.75 (m, 2H), 1.92 (m, 5H).

(980) MS (ESI, m/z): 503.6 [M+H.sup.+].

Example 119: (R)-4-oxo-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-7-carboxylic acid ethyl ester

(981) Starting from the compounds of Preparations BF and AU and using procedure E, the title compound was obtained as a colourless solid (910 mg, 66% yield).

(982) MS (ESI, m/z): 549.2 [M+H.sup.+]

Example 120: (R)-7-hydroxymethyl-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(983) Starting from the compounds of Preparations BG and AU and using procedure E, the title compound was obtained as a beige solid (40 mg, 16% yield).

(984) MS (ESI, m/z): 507.2 [M+H.sup.+].

Example 121: (R)-4-oxo-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-7-carboxylic acid hydrochloride

(985) A suspension of the compound of Example 119 (100 mg) in 6M HCl (0.6 mL) was stirred at 90° C. for 6 h. The reaction mixture was evaporated under reduced pressure and the residue was taken up in MeOH and collected by filtration, affording a beige solid (37 mg; 36% yield).

(986) MS (ESI, m/z): 521.5 [M+H*].

Example 122: (R)-7-dimethylaminomethyl-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(987) Starting from the compounds of Preparations BH and AU and using procedure E, the title compound was obtained as a beige solid (39 mg; 30% yield).

(988) MS (ESI, m/z): 534.5 [M+H.sup.+].

Example 123: (R)-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-7-pyrrolidin-1-ylmethyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(989) Starting from the compounds of Preparations BI and AU and using procedure E, the title compound was obtained as a beige foam (50 mg, 27% yield).

(990) MS (ESI, m/z): 560.6 [M+H.sup.+].

Example 124: (RS)-9-fluoro-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(991) Starting from the compounds of Preparations C and BJ and using procedure E, the title compound was obtained as a colourless foam (87 mg, 60% yield).

(992) MS (ESI, m/z): 480.5 [M+H.sup.+].

Example 125: (RS)-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(993) Starting from the compounds of Preparations C and BK and using procedure E, the title compound was obtained as a colourless solid (84 mg, 49% yield).

(994) .sup.1H NMR (CDCl.sub.3) δ: 8.04 (m, 1H), 7.88 (dd, J=8.5, 2.9 Hz, 1H), 7.68 (dd, J=9.4, 1.2 Hz, 1H), 7.60 (dd, J=8.5, 1.5 Hz, 1H), 7.47 (dd, J=8.8, 4.7 Hz, 1H), 6.91 (t, J=9.1 Hz, 1H), 6.63 (d, J=9.4 Hz, 1H), 5.00 (m, 1H), 4.66 (m, 1H), 4.51 (m, 1H), 4.27 (m, 2H), 3.77 (dt, J=10.3, 6.7 Hz, 1H), 3.47 (s, 2H), 2.77 (m, 2H), 1.80 (m, 4H).

(995) MS (ESI, m/z): 496.6 [M+H.sup.+].

Example 126: (RS)-9-fluoro-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(996) Starting from the compounds of Preparations C and BL and using procedure E, the title compound was obtained as a colourless solid (54 mg, 32% yield).

(997) .sup.1H NMR (CDCl.sub.3) δ: 8.03 (m, 1H), 7.88 (dd, J=8.8, 2.9 Hz, 1H), 7.68 (dd, J=9.4, 0.9 Hz, 1H), 7.60 (dd, J=8.5, 1.5 Hz, 1H), 7.47 (dd, J=8.8, 4.7 Hz, 1H), 6.91 (t, J=9.1 Hz, 1H), 6.63 (d, J=9.4 Hz, 1H), 5.00 (m, 1H), 4.66 (m, 1H), 4.51 (m, 1H), 4.28 (m, 2H), 3.77 (dt, J=10.5, 7.0 Hz, 1H), 3.47 (s, 2H), 2.77 (m, 2H), 1.80 (m, 4H).

(998) MS (ESI, m/z): 496.6 [M+H.sup.+].

Examples 127 and 128

(R)-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one and (S)-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(999) The product of Example 13 was separated by preparative chiral HPLC using a 5 μm (R,R)-Whelk-01 column (21.1×250 mm) eluting with 1:1 MeCN-EtOH containing 0.1% of diethylamine with t.sub.R=7.25 min (compound of Example 127, 100% ee) and t.sub.R=10.26 min (compound of Example 128, 100% ee).

(1000) Data obtained for the compound of Example 127:

(1001) .sup.1H NMR (CDCl.sub.3) δ: 7.69 (d, J=9.7 Hz, 1H), 7.47 (dd, J=8.8, 4.7 Hz, 1H), 7.31 (d, J=2.3 Hz, 1H), 7.22 (d, J=8.5 Hz, 1H), 6.91 (m, 2H), 6.60 (d, J=9.4 Hz, 1H), 4.95 (dd, J=8.2, 3.5 Hz, 1H), 4.64 (m, 1H), 4.48 (m, 1H), 4.26 (dd, J=13.5, 3.5 Hz, 1H), 4.04 (t, J=8.8 Hz, 1H), 3.59 (dd, J=8.8, 7.0 Hz, 1H), 3.34 (s, 2H), 2.73 (m, 2H), 1.76 (m, 4H).

(1002) MS (ESI, m/z): 495.3 [M+H.sup.+].

(1003) Data obtained for the compound of Example 128:

(1004) .sup.1H NMR (CDCl.sub.3) δ: 7.68 (d, J=9.4 Hz, 1H), 7.46 (dd, J=8.5, 4.7 Hz, 1H), 7.31 (d, J=2.3 Hz, 1H), 7.21 (d, J=8.5 Hz, 1H), 6.90 (m, 2H), 6.59 (d, J=9.4 Hz, 1H), 4.94 (dd, J=8.2, 2.9 Hz, 1H), 4.62 (m, 1H), 4.47 (dd, J=13.2, 8.2 Hz, 1H), 4.24 (dd, J=13.5, 3.5 Hz, 1H), 4.02 (t, J=8.5 Hz, 1H), 3.60 (m, 1H), 3.33 (s, 2H), 2.72 (m, 2H), 1.74 (m, 4H).

(1005) MS (ESI, m/z): 495.3 [M+H.sup.+].

Examples 129 and 130

(R)-9-fluoro-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one and (S)-9-fluoro-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1006) First Step:

(1007) Starting from the compound of Example 4 and 3-(tert-butyldimethylsilyloxy)-propionaldehyde and using procedure E, the title compound was obtained as a yellow foam (82 mg; 87% yield).

(1008) MS (ESI, m/z): 667.4 [M+H.sup.+].

(1009) Second Step:

(1010) The product from the first step was separated by preparative chiral HPLC using a 5 μm (R,R)-Whelk-01 column (21.1×250 mm) eluting with 1:1 MeCN-EtOH containing 0.1% of diethylamine with t.sub.R=7.41 min (compound of Example 129, 100% ee) and t.sub.R=10.35 min (compound of Example 130, 100% ee).

(1011) Data obtained for the compound of Example 129:

(1012) .sup.1H NMR (CDCl.sub.3) δ: 7.68 (d, J=9.4 Hz, 1H), 7.46 (dd, J=8.8, 4.7 Hz, 1H), 7.30 (d, J=2.1 Hz, 1H), 7.20 (d, J=8.5 Hz, 1H), 6.90 (m, 2H), 6.58 (d, J=9.4 Hz, 1H), 4.94 (dd, J=8.2, 3.2 Hz, 1H), 4.63 (m, 1H), 4.46 (dd, J=13.5, 8.5 Hz, 1H), 4.23 (dd, J=13.5, 3.5 Hz, 1H), 4.02 (t, J=8.5 Hz, 1H), 3.58 (dd, J=7.9, 7.0 Hz, 1H), 3.33 (s, 2H), 2.72 (m, 2H), 1.74 (m, 4H).

(1013) MS (ESI, m/z): 495.4 [M+H.sup.+].

(1014) Data obtained for the compound of Example 130:

(1015) .sup.1H NMR (CDCl.sub.3) δ: 7.68 (d, J=9.4 Hz, 1H), 7.46 (dd, J=8.8, 4.7 Hz, 1H), 7.30 (d, J=2.3 Hz, 1H), 7.21 (d, J=8.5 Hz, 1H), 6.90 (m, 2H), 6.59 (d, J=9.4 Hz, 1H), 4.94 (dd, J=8.5, 3.5 Hz, 1H), 4.64 (m, 1H), 4.47 (m, 1H), 4.24 (dd, J=13.2, 3.5 Hz, 1H), 4.03 (t, J=8.5 Hz, 1H), 3.59 (dd, J=8.8, 7.0 Hz, 1H), 3.33 (s, 2H), 2.71 (m, 2H), 1.75 (m, 4H).

(1016) MS (ESI, m/z): 495.4 [M+H.sup.+].

Example 131: (R)-7-fluoro-6-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

(1017) Starting from the compounds of Preparations AA and BJ and using procedure E, the title compound was obtained as a yellowish solid (61 mg, 42% yield).

(1018) .sup.1H NMR (DMSO-d6) δ: 11.14 (s, 1H), 8.13 (s, 1H), 7.76 (dd, J=8.8, 4.4 Hz, 1H), 7.56 (m, 1H), 7.39 (d, J=8.8 Hz, 1H), 7.13 (t, J=9.1 Hz, 1H), 4.66 (s, 1H), 4.58 (s, 3H), 4.44 (m, 1H), 4.18 (m, 1H), 4.08 (dd, J=13.2, 3.2 Hz, 1H), 3.67 (dd, J=10.0, 7.0 Hz, 1H), 2.60 (m, 2H), 1.74 (m, 2H), 1.49 (m, 2H).

(1019) MS (ESI, m/z): 481.4 [M+H.sup.+].

Example 132: (R)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

(1020) Starting from the compounds of Preparations AA and BK and using procedure E, the title compound was obtained as a colourless solid (50 mg, 50% yield).

(1021) .sup.1H NMR (DMSO-d6) δ: 10.81 (s, 1H), 8.13 (s, 1H), 7.77 (m, 2H), 7.66 (m, 1H), 7.13 (t, J=9.1 Hz, 1H), 4.90 (m, 1H), 4.69 (m, 1H), 4.44 (dd, J=12.9, 8.2 Hz, 1H), 4.19 (m, 1H), 4.08 (m, 1H), 3.68 (dd, J=10.0, 7.0 Hz, 1H), 3.51 (s, 2H), 2.60 (dd, J=1.2, 0.6 Hz, 2H), 1.75 (m, 2H), 1.50 (m, 2H).

Example 133: (R)-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1022) Starting from the compounds of Preparations BC and AU and using procedure E, the title compound was obtained as a yellow solid (54 mg, 45% yield).

(1023) MS (ESI, m/z): 477.2 [M+H.sup.+].

Example 134: (R)-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1024) Starting from the compounds of Preparations BC and AV and using procedure E, the title compound was obtained as a colourless solid (80 mg, 69% yield).

(1025) MS (ESI, m/z): 461.2 [M+H.sup.+].

Example 135: (R)-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1026) Starting from the compounds of Preparations BC and BJ and using procedure E, the title compound was obtained as an off-white solid (75 mg, 65% yield).

(1027) MS (ESI, m/z): 462.1 [M+H.sup.+].

Example 136: (S)-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1028) Starting from the compounds of Preparations AS and BL and using procedure E, the title compound was obtained as a beige solid (31 mg, 33% yield).

(1029) .sup.1H NMR (DMSO-d6) δ: 10.82 (s, 1H), 7.89 (d, J=9.7 Hz, 1H), 7.77 (m, 1H), 7.66 (m, 1H), 7.55 (m, 2H), 7.18 (t, J=7.6 Hz, 1H), 6.54 (d, J=9.4 Hz, 1H), 4.70 (m, 2H), 4.37 (m, 1H), 4.19 (m, 1H), 4.00 (m, 1H), 3.69 (m, 1H), 3.51 (s, 2H), 2.64 (m, 2H), 1.76 (m, 2H), 1.52 (m, 2H).

(1030) MS (ESI, m/z): 478.2 [M+H.sup.+].

Example 137: (S)-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1031) Starting from the compounds of Preparations AS and BK and using procedure E, the title compound was obtained as an off-white foam (143 mg, 60% yield).

(1032) MS (ESI, m/z): 478.2 [M+H.sup.+].

Example 138: (R)-3-fluoro-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(1033) Starting from the compounds of Preparations BM and U and using procedure E, the title compound was obtained as an off-white foam (17 mg, 14% yield).

(1034) .sup.1H NMR (CDCl.sub.3) δ: 9.04 (s, 1H), 8.36 (s, 1H), 7.87 (m, 1H), 7.41 (d, J=2.1 Hz, 1H), 7.23 (m, 1H), 6.84 (m, 2H), 5.04 (dd, J=8.5, 3.8 Hz, 1H), 4.59 (m, 2H), 4.28 (dd, J=13.5, 3.8 Hz, 1H), 4.04 (t, J=8.8 Hz, 1H), 3.59 (m, 1H), 3.36 (s, 2H), 2.80 (m, 2H), 1.83 (m, 5H).

(1035) MS (ESI, m/z): 496.3 [M+H.sup.+].

Example 139: (R)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(1036) Starting from the compounds of Preparations BM and AU and using procedure E, the title compound was obtained as a yellowish foam (10 mg, 8% yield).

(1037) .sup.1H NMR (CDCl.sub.3) δ: 8.37 (s, 1H), 7.90 (m, 1H), 7.32 (d, J=2.6 Hz, 1H), 7.24 (m, 2H), 6.90 (m, 1H), 6.82 (d, J=9.7 Hz, 1H), 5.06 (m, 1H), 4.60 (m, 2H), 4.30 (m, 1H), 4.05 (t, J=8.8 Hz, 1H), 3.61 (m, 1H), 3.35 (s, 2H), 2.81 (m, 2H), 1.79 (m, 4H).

(1038) MS (ESI, m/z): 496.6 [M+H.sup.+].

Example 140: (R)-3-fluoro-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(1039) Starting from the compounds of Preparations BM and T and using procedure E, the title compound was obtained as yellowish foam (6 mg, 5%).

(1040) .sup.1H NMR (CDCl.sub.3) δ: 8.36 (d, J=1.2 Hz, 1H), 7.89 (d, J=9.7 Hz, 1H), 7.30 (d, J=2.6 Hz, 1H), 6.81 (m, 3H), 5.03 (m, 1H), 4.59 (m, 4H), 4.26 (dd, J=13.2, 3.8 Hz, 1H), 4.03 (t, J=8.5 Hz, 1H), 3.58 (m, 1H), 2.77 (m, 2H), 1.77 (m, 5H).

(1041) MS (ESI, m/z): 480.6 [M+H.sup.+].

Example 141: (R)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(1042) Starting from the compounds of Preparations BM and AV and using procedure E, the title compound was obtained as a yellowish foam (8 mg, 7% yield).

(1043) .sup.1H NMR (CDCl.sub.3) δ: 8.37 (d, J=1.5 Hz, 1H), 7.90 (d, J=9.7 Hz, 1H), 7.36 (d, J=2.3 Hz, 1H), 6.90 (m, 1H), 6.83 (d, J=9.4 Hz, 1H), 6.73 (dd, J=8.8, 2.6 Hz, 1H), 5.03 (m, 1H), 4.59 (m, 4H), 4.25 (dd, J=13.2, 3.8 Hz, 1H), 4.04 (t, J=8.5 Hz, 1H), 3.59 (m, 1H), 2.76 (m, 2H), 1.78 (m, 5H).

(1044) MS (ESI, m/z): 480.6 [M+H.sup.+].

Example 142: (R)-3-fluoro-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(1045) Starting from the compounds of Preparations BM and BK and using procedure E, the title compound was obtained as a yellowish solid (24 mg, 20% yield).

(1046) .sup.1H NMR (DMSO-d.sub.6) δ: 10.81 (s, 1H), 8.45 (d, J=0.9 Hz, 1H), 7.96 (d, J=9.7 Hz, 1H), 7.77 (m, 1H), 7.66 (m, 1H), 6.75 (d, J=9.7 Hz, 1H), 4.95 (m, 1H), 4.70 (m, 1H), 4.44 (dd, J=12.9, 8.5 Hz, 1H), 4.19 (m, 1H), 4.04 (dd, J=12.9, 3.5 Hz, 1H), 3.69 (dd, J=10.3, 7.0 Hz, 1H), 3.51 (s, 2H), 2.67 (m, 3H), 1.75 (m, 2H), 1.51 (m, 2H).

(1047) MS (ESI, m/z): 497.4 [M+H.sup.+].

Example 143: (R)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(1048) Starting from the compounds of Preparations BM and BL and using procedure E, the title compound was obtained as an off-white solid (26 mg, 21% yield).

(1049) .sup.1H NMR (DMSO-d.sub.6) δ: 10.81 (s, 1H), 8.45 (d, J=0.6 Hz, 1H), 7.96 (dd, J=9.7, 0.6 Hz, 1H), 7.77 (m, 1H), 7.66 (m, 1H), 6.75 (d, J=9.7 Hz, 1H), 4.95 (m, 1H), 4.70 (m, 1H), 4.44 (m, 1H), 4.19 (m, 1H), 4.04 (dd, J=12.6, 3.5 Hz, 1H), 3.69 (m, 1H), 3.51 (s, 3H), 2.67 (m, 3H), 1.76 (m, 2H), 1.52 (m, 2H).

(1050) MS (ESI, m/z): 497.3 [M+H.sup.+].

Example 144: (R)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(1051) Starting from the compounds of Preparations BM and BJ and using procedure E, the title compound was obtained as a colourless solid (20 mg, 17% yield).

(1052) .sup.1H NMR (DMSO-d.sub.6) δ: 11.15 (s, 1H), 8.45 (d, J=1.5 Hz, 1H), 7.96 (d, J=9.7 Hz, 1H), 7.57 (m, 1H), 7.40 (m, 1H), 6.75 (d, J=9.7 Hz, 1H), 4.95 (m, 1H), 4.67 (m, 1H), 4.58 (s, 2H), 4.44 (dd, J=12.9, 8.5 Hz, 1H), 4.18 (m, 1H), 4.04 (dd, J=12.6, 3.5 Hz, 1H), 3.69 (m, 1H), 2.68 (m, 3H), 1.75 (m, 2H), 1.52 (m, 2H).

(1053) MS (ESI, m/z): 481.5 [M+H.sup.+].

Example 145: (S)-3-fluoro-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(1054) Starting from the compounds of Preparations BN and U and using procedure E, the title compound was obtained as a yellowish foam (16 mg, 13% yield).

(1055) .sup.1H NMR (CDCl.sub.3) δ: 8.37 (d, J=1.2 Hz, 1H), 7.89 (d, J=9.7 Hz, 1H), 7.31 (d, J=2.3 Hz, 1H), 7.22 (d, J=8.5 Hz, 1H), 6.91 (dd, J=8.5, 2.3 Hz, 1H), 6.81 (d, J=9.7 Hz, 1H), 5.08 (m, 1H), 4.60 (m, 2H), 4.32 (m, 1H), 4.05 (m, 1H), 3.60 (m, 1H), 3.34 (s, 2H), 2.83 (m, 2H), 1.85 (m, 4H).

(1056) MS (ESI, m/z): 496.5 [M+H.sup.+].

Example 146: (S)-3-fluoro-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(1057) Starting from the compounds of Preparations BN and T and using procedure E, the title compound was obtained as a yellow foam (7 mg, 6% yield).

(1058) MS (ESI, m/z): 480.6 [M+H.sup.+].

Example 147: (S)-3-fluoro-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(1059) Starting from the compounds of Preparations BN and BK and using procedure E, the title compound was obtained as a colourless solid (13 mg, 11% yield).

(1060) .sup.1H NMR (DMSO-d.sub.6) δ: 10.82 (s, 1H), 8.45 (s, 1H), 7.96 (d, J=10.0 Hz, 1H), 7.77 (m, 1H), 7.66 (m, 1H), 6.75 (d, J=10.0 Hz, 1H), 4.96 (m, 1H), 4.69 (m, 1H), 4.44 (m, 1H), 4.19 (m, 1H), 4.04 (m, 1H), 3.69 (m, 1H), 3.50 (s, 2H), 2.66 (m, 2H), 1.75 (m, 2H), 1.51 (m, 2H).

(1061) MS (ESI, m/z): 497.6 [M+H.sup.+].

Example 148: (S)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(1062) Starting from the compounds of Preparations BN and AU and using procedure E, the title compound was obtained as a yellowish foam (30 mg, 25% yield).

(1063) .sup.1H NMR (CDCl.sub.3) δ: 8.36 (d, J=1.5 Hz, 1H), 7.89 (d, J=10.0 Hz, 1H), 7.32 (d, J=2.3 Hz, 1H), 7.22 (d, J=8.5 Hz, 1H), 6.90 (dd, J=8.5, 2.3 Hz, 1H), 6.81 (d, J=9.7 Hz, 1H), 5.04 (ddd, J=8.5, 4.1, 0.6 Hz, 1H), 4.59 (m, 2H), 4.27 (dd, J=13.2, 3.8 Hz, 1H), 4.05 (m, 1H), 3.60 (dd, J=9.1, 7.3 Hz, 1H), 3.35 (s, 2H), 2.79 (m, 2H), 1.78 (m, 5H).

(1064) MS (ESI, m/z): 496.6 [M+H.sup.+].

Example 149: (S)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(1065) Starting from the compounds of Preparations BN and AV and using procedure E, the title compound was obtained as a yellow foam (8 mg, 7% yield).

(1066) MS (ESI, m/z): 480.5 [M+H.sup.+].

Example 150: (S)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(1067) Starting from the compounds of Preparations BN and BL and using procedure E, the title compound was obtained as an orange foam (6 mg, 5% yield).

(1068) MS (ESI, m/z): 497.4 [M+H.sup.+]

Example 151: (S)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(1069) Starting from the compounds of Preparations BN and BJ and using procedure E, the title compound was obtained as a yellowish solid (11 mg, 9% yield).

(1070) .sup.1H NMR (DMSO-d.sub.6) δ: 11.15 (s, 1H), 8.45 (s, 1H), 7.96 (d, J=9.7 Hz, 1H), 7.57 (m, 1H), 7.40 (m, 1H), 6.75 (d, J=10.0 Hz, 1H), 4.96 (m, 1H), 4.67 (m, 1H), 4.58 (s, 2H), 4.44 (m, 1H), 4.19 (m, 1H), 4.05 (m, 1H), 3.68 (m, 1H), 2.66 (m, 2H), 1.76 (m, 2H), 1.51 (m, 3H).

(1071) MS (ESI, m/z): 481.5 [M+H.sup.+].

Example 152: (RS)-9-methyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1072) Starting from the compounds of Preparations BO and U and using procedure E, the title compound was obtained as a colourless solid (32 mg, 38% yield).

(1073) MS (ESI, m/z): 491.2 [M+H.sup.+].

Example 153: (RS)-9-fluoro-1-(methyl-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-amino)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1074) A suspension of the compound of Example 152 (20 mg) in MeOH (2 mL) was treated with an aq. formaldehyde solution (37%; 16 μL) for 10 min, then treated with NaBH.sub.3CN (2.5 mg). After 3 h stirring at rt, the reaction mixture was taken up in water and extracted with EA. The org. layer was washed with water, brine and dried over MgSO.sub.4. The org. layer was filtrated and evaporated under reduced pressure and the residue was purified by CC (DCM/MeOH/NH.sub.4OH 100:50:4), affording a colourless foam (9 mg; 44% yield).

(1075) .sup.1H NMR (CDCl.sub.3) δ: 8.50 (s, 1H), 7.70 (d, J=9.7 Hz, 1H), 7.48 (dd, J=8.5, 4.4 Hz, 1H), 7.40 (d, J=2.1 Hz, 1H), 7.27 (m, 1H), 6.94 (m, 2H), 6.64 (d, J=9.4 Hz, 1H), 5.03 (t, J=6.4 Hz, 1H), 4.67 (m, 1H), 4.38 (d, J=6.4 Hz, 2H), 4.08 (m, 1H), 3.62 (m, 1H), 3.40 (s, 2H), 2.50 (m, 2H), 2.22 (d, J=4.1 Hz, 3H), 1.77 (m, 4H).

(1076) MS (ESI, m/z): 509.3 [M+H.sup.+].

Example 154: (RS)-6-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

(1077) Starting from the compounds of Preparations AC and H and using procedure C, the title compound was obtained as a yellowish foam (82 mg, 35% yield).

(1078) MS (ESI, m/z): 462.1 [M+H.sup.+]

Example 155: (RS)-6-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

(1079) Starting from the compounds of Preparations AC and I and using procedure C, the title compound was obtained as yellow foam (90 mg, 39% yield).

(1080) MS (ESI, m/z): 462.1 [M+H.sup.+].

Example 156: (RS)-6-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

(1081) Starting from the compounds of Preparations AC and J and using procedure C, the title compound was obtained as a brown foam (270 mg, 37% yield).

(1082) MS (ESI, m/z): 478.2 [M+H.sup.+].

Example 157: (R)-1-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1083) Starting from the compounds of Preparations BC and H and using procedure C, the title compound was obtained as a yellowish foam (59 mg, 26% yield).

(1084) MS (ESI, m/z): 447.2 [M+H.sup.+].

Example 158: (R)-1-{2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1085) Starting from the compounds of Preparations BC and J and using procedure C, the title compound was obtained as a brown foam (81 mg, 35% yield).

(1086) MS (ESI, m/z): 463.2 [M+H.sup.+].

Example 159: (RS)-9-fluoro-1-{4-[(RS)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-butylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1087) Starting from the compounds of Preparations C and BP and using procedure E, the title compound was obtained as a colourless foam (84 mg, 55% yield).

(1088) MS (ESI, m/z): 509.1 [M+H.sup.+].

Example 160: (S)-7-fluoro-6-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2,5,6-tetrahydro-pyrrolo[1,2,3-de]quinoxalin-3-one

(1089) A solution of the compound of Example 79 (42 mg) in DCM/MeOH (2:1; 6 mL) was treated with NaBH.sub.4 (3.2 mg). After 30 min stirring at rt, the reaction mixture was quenched with 1M HCl (1 mL) and partitioned between DCM and aq. NH.sub.4OH. The org. layer was washed with water, dried over MgSO.sub.4, concentrated under reduced pressure and purified by CC (EA/MeOH 19:1 to 9:1), affording a beige solid (29 mg; 69% yield).

(1090) MS (ESI, m/z): 498.2 [M+H.sup.+].

Example 161: (1R,2R)-4-oxo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylic acid methyl ester and (1S,2S)-4-oxo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylic acid methyl ester

(1091) Starting from the compounds of Preparations BQ and U and using procedure E, a mixture of the title compounds was obtained as a yellowish solid (46 mg, 23% yield).

(1092) MS (ESI, m/z): 535.6 [M+H.sup.+].

Example 162: (1R,2R)-4-oxo-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylic acid methyl ester and (1S,2S)-4-oxo-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylic acid methyl ester

(1093) Starting from the compounds of Preparations BQ and AU and using procedure E, a mixture of the title compounds was obtained as a colourless solid (67 mg, 32% yield).

(1094) MS (ESI, m/z): 535.7 [M+H.sup.+].

Example 163: (1R,2R)-2-hydroxymethyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one and (1S,2S)-2-hydroxymethyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1095) Starting from the compounds of Preparations BR and U and using procedure E, a mixture of the title compounds was obtained as a colourless solid (99 mg, 54% yield).

(1096) MS (ESI, m/z): 507.2 [M+H.sup.+].

Example 164: (1R,2R)-2-hydroxymethyl-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one and (1S,2S)-2-hydroxymethyl-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1097) Starting from the compounds of Preparations BR and AU and using procedure E, a mixture of the title compounds was obtained as a colourless solid (110 mg, 60% yield).

(1098) MS (ESI, m/z): 507.2 [M+H.sup.+].

Example 165: (1R,2R)-2-methoxymethyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one and (1S,2S)-2-methoxymethyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1099) Starting from the compounds of Preparations BS and U and using procedure E, a mixture of the title compounds was obtained as a colourless solid (20 mg, 32% yield).

(1100) MS (ESI, m/z): 521.6 [M+H.sup.+].

Example 166: (1R,2S)-2-methyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one and (1S,2R)-2-methyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1101) Starting from the compounds of Preparations BT and U and using procedure E, a mixture of the title compounds was obtained as a colourless solid (56 mg, 38% yield).

(1102) .sup.1H NMR (CDCl.sub.3) δ: 8.57 (s, 1H), 7.71 (dd, J=9.4, 0.6 Hz, 1H), 7.52 (m, 2H), 7.33 (m, 1H), 7.23 (m, 2H), 6.99 (m, 1H), 6.69 (dd, J=9.4, 1.5 Hz, 1H), 4.82 (d, J=6.4 Hz, 1H), 4.65 (m, 1H), 4.26 (s, 1H), 4.05 (td, J=8.5, 6.2 Hz, 1H), 3.63 (m, 1H), 3.39 (s, 2H), 2.80 (m, 2H), 1.87 (m, 5H), 1.56 (d, J=6.7 Hz, 3H).

(1103) MS (ESI, m/z): 491.3 [M+H.sup.+].

Example 167: (1R,2S)-2-methyl-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one and (1S,2R)-2-methyl-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1104) Starting from the compounds of Preparations BT and AU and using procedure E, a mixture of the title compounds was obtained as a colourless solid (59 mg, 40% yield).

(1105) .sup.1H NMR (CDCl.sub.3) δ: 8.60 (dd, J=2.3, 0.6 Hz, 1H), 7.71 (dd, J=9.4, 0.9 Hz, 1H), 7.51 (m, 2H), 7.33 (dd, J=14.4, 2.3 Hz, 1H), 7.24 (m, 2H), 6.98 (td, J=8.2, 2.3 Hz, 1H), 6.69 (dd, J=9.4, 1.8 Hz, 1H), 4.80 (dt, J=6.4, 1.8 Hz, 1H), 4.64 (m, 1H), 4.24 (s, 1H), 4.05 (td, J=8.5, 5.9 Hz, 1H), 3.61 (dd, J=8.8, 7.0 Hz, 1H), 3.39 (s, 2H), 2.80 (m, 2H), 1.79 (m, 5H), 1.55 (d, J=6.4 Hz, 3H).

(1106) MS (ESI, m/z): 491.3 [M+H.sup.+].

Example 168: (1R,2S)-2-methyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one and (1S,2R)-2-methyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1107) Starting from the compounds of Preparations BT and BK and using procedure E, a mixture of the title compounds was obtained as a colourless solid (42 mg, 24% yield).

(1108) .sup.1H NMR (CDCl.sub.3) δ: 8.50 (s, 1H), 7.81 (m, 1H), 7.68 (dd, J=9.4, 5.6 Hz, 1H), 7.51 (m, 3H), 7.19 (m, 1H), 6.63 (dd, J=9.4, 5.0 Hz, 1H), 4.76 (m, 1H), 4.62 (d, J=7.9 Hz, 1H), 4.18 (m, 2H), 3.72 (m, 1H), 3.43 (s, 2H), 2.76 (m, 2H), 1.77 (m, 5H), 1.53 (d, J=6.4 Hz, 3H).

(1109) MS (ESI, m/z): 492.3 [M+H.sup.+].

Example 169: (1R,2S)-2-methyl-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one and (1S,2R)-2-methyl-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1110) Starting from the compounds of Preparations BT and BL and using procedure E, a mixture of the title compounds was obtained as a colourless solid (43 mg, 24% yield).

(1111) .sup.1H NMR (CDCl.sub.3) δ: 8.10 (m, 1H), 7.86 (dd, J=8.8, 3.8 Hz, 1H), 7.71 (dd, J=9.4, 1.5 Hz, 1H), 7.55 (m, 3H), 7.22 (m, 1H), 6.67 (d, J=9.4 Hz, 1H), 4.83 (m, 1H), 4.64 (m, 1H), 4.22 (m, 2H), 3.75 (dt, J=10.5, 7.3 Hz, 1H), 3.46 (s, 2H), 2.79 (m, 2H), 1.87 (m, 5H), 1.57 (dd, J=6.4, 1.2 Hz, 3H).

(1112) MS (ESI, m/z): 492.4 [M+H.sup.+].

Example 170: (1R,2R)-2-(1-hydroxy-1-methyl-ethyl)-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one and (1S,2S)-2-(1-hydroxy-1-methyl-ethyl)-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1113) Starting from the compounds of Preparations BU and U and using procedure E, a mixture of the title compounds was obtained as a colourless foam (22 mg, 46% yield).

(1114) MS (ESI, m/z): 535.6 [M+H.sup.+].

Example 171: (R)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2,5,6-tetrahydro-pyrrolo[1,2,3-de]quinoxalin-3-one

(1115) Starting from the compound of Example 132 and proceeding in analogy to Example 160, the title compound was obtained as a colourless foam (36% yield).

(1116) MS (ESI, m/z): 499.4 [M+H.sup.+].

Example 172: N—((RS)-9-fluoro-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-N-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-acetamide and (RS)-1-{3-[(R)-3-(4-acetyl-3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-2-oxo-oxazolidin-5-yl]-propylamino}-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1117) A solution of the compound of Example 13 (20 mg) and DIPEA (14 μL) was reacted at 0° C. with Ac.sub.2O (6 μL). The reaction mixture was further stirred at rt for 5 h. The solvent was removed under reduced pressure and the residue was dissolved in DCM and sequentially washed with water and brine. The org. layer was dried over MgSO.sub.4. The solvent was removed under reduced pressure and the residue was purified by CC (DCM/MeOH/NH.sub.4OH; 1000:50:4), affording a 1:1-mixture of the two possible N-acetates as an off-white foam (18 mg; 83% yield).

(1118) MS (ESI, m/z): 537.5 [M+H.sup.+].

Example 173: (S)-4-hydroxy-4-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

(1119) To a solution of the compound of Preparation BD (75 mg) in EtOH (3 mL) were added the compound of Preparation AP (89 mg, 1.5 eq.) and K.sub.2CO.sub.3 (65 mg, 3 eq.). The mixture was stirred at rt for 3 days. The solvent was removed under reduced pressure and the residue was partitioned between water and DCM-MeOH (9:1). The phases were separated and the aq. layer was extracted two more times with DCM-MeOH (9:1). The combined org. layers were dried over MgSO.sub.4 and concentrated. The residue was purified by CC (DCM/MeOH/NH.sub.4OH 1000:100:8) to afford the title compound as a yellow solid (26 mg, 26% yield).

(1120) MS (ESI, m/z): 494.2 [M+H.sup.+].

Example 174: (RS)-9-fluoro-1-hydroxy-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1121) Starting from 9-fluoro-1-hydroxy-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl]methyl 4-methylbenzenesulfonate (prepared according to EP 1980251) and the compound of Preparation AP and using procedure C, the title compound was obtained as a yellow solid (85 mg, 65% yield).

(1122) MS (ESI, m/z): 511.2 [M+H.sup.+].

Example 175: (RS)-1-({[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1123) Starting from the compounds of Preparations AE and BW and using procedure C, the title compound was obtained as a beige solid (70 mg; 20% yield).

(1124) MS (ESI, m/z): 464.4 [M+H.sup.+].

Example 176: (RS)-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1125) Starting from the compounds of Preparations AE and BX and using procedure C, the title compound was obtained as a colourless solid (130 mg; 36% yield).

(1126) MS (ESI, m/z): 478.2 [M+H.sup.+].

Example 177: (RS)-9-chloro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1127) Starting from the compounds of Preparations BY and BK and using procedure E, the title compound was obtained as a pale yellow solid (31 mg; 58% yield).

(1128) .sup.1H NMR (CDCl.sub.3) δ: 8.33 (m, 1H), 7.84 (dd, J=8.8, 4.4 Hz, 1H), 7.66 (dd, J=9.4, 3.5 Hz, 1H), 7.57 (dd, J=8.5, 2.3 Hz, 1H), 7.41 (dd, J=8.2, 1.8 Hz, 1H), 7.11 (dd, J=8.5, 1.5 Hz, 1H), 6.66 (dd, J=9.4, 3.8 Hz, 1H), 4.91 (m, 1H), 4.62 (m, 1H), 4.45 (m, 1H), 4.25 (m, 2H), 3.75 (m, 1H), 3.45 (s, 2H), 2.61 (m, 2H), 1.78 (m, 5H).

(1129) MS (ESI, m/z): 512.3 [M+H.sup.+].

Example 178: (RS)-9-chloro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1130) Starting from the compounds of Preparations BY and U and using procedure E, the title compound was obtained as a colourless solid (14 mg; 26% yield).

(1131) .sup.1H NMR (CDCl3) δ: 8.73 (s, 1H), 7.68 (d, J=9.7 Hz, 1H), 7.39 (m, 2H), 7.25 (m, 1H), 7.12 (d, J=8.2 Hz, 1H), 6.98 (m, 1H), 6.68 (d, J=9.4 Hz, 1H), 4.91 (dd, J=8.2, 3.5 Hz, 1H), 4.65 (m, 1H), 4.46 (m, 1H), 4.30 (dd, J=13.2, 3.2 Hz, 1H), 4.06 (m, 1H), 3.61 (m, 1H), 3.39 (s, 2H), 2.64 (m, 2H), 1.86 (m, 5H).

(1132) MS (ESI, m/z): 511.3 [M+H.sup.+].

Example 179: (RS)-9-ethyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1133) Starting from the compounds of Preparations BZ and U and using procedure E, the title compound was obtained as a colourless solid (11 mg; 36% yield).

(1134) .sup.1H NMR (CDCl3) δ: 8.56 (m, 1H), 7.68 (d, J=9.4 Hz, 1H), 7.39 (m, 2H), 7.26 (m, 1H), 7.01 (m, 2H), 6.64 (d, J=9.4 Hz, 1H), 4.82 (t, J=5.3 Hz, 1H), 4.65 (m, 1H), 4.37 (d, J=5.3 Hz, 2H), 4.06 (m, 1H), 3.61 (dd, J=8.5, 7.0 Hz, 1H), 3.39 (s, 2H), 2.80 (m, 4H), 1.71 (m, 5H), 1.29 (m, 3H).

(1135) MS (ESI, m/z): 505.5 [M+H.sup.+].

Example 180: (RS)-9-ethynyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1136) Starting from the compounds of Preparations CA and U and using procedure E, the title compound was obtained as a colourless solid (10 mg; 21% yield).

(1137) MS (ESI, m/z): 501.2 [M+H.sup.+].

Example 181: (1R*,2R*)-9-fluoro-4-oxo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylic acid methyl ester

(1138) Starting from the compounds of Preparations CB and U and using procedure E, the title compound was obtained as an off-white foam (23 mg; 20% yield).

(1139) MS (ESI, m/z): 553.6 [M+H.sup.+].

Example 182: (1R*,2R*)-9-fluoro-2-hydroxymethyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1140) Starting from the compounds of Preparations CC and U and using procedure E, the title compound was obtained as a white foam (44 mg; 38% yield).

(1141) MS (ESI, m/z): 525.3 [M+H.sup.+].

Example 183: (1R*,2S*)-9-fluoro-2-methyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1142) Starting from the compounds of Preparations CD and U and using procedure E, the title compound was obtained as an off-white foam (12 mg; 10% yield).

(1143) MS (ESI, m/z): 509.3 [M+H.sup.+].

Example 184: (1R*,2S*)-9-fluoro-2-methyl-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1144) Starting from the compounds of Preparations CD and AU and using procedure E, the title compound was obtained as an off-white foam (21 mg; 18% yield).

(1145) MS (ESI, m/z): 509.3 [M+H.sup.+].

Example 185: (1R*,2S*)-9-fluoro-2-methyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1146) Starting from the compounds of Preparations CD and BK and using procedure E, the title compound was obtained as an off-white foam (64 mg; 55% yield).

(1147) MS (ESI, m/z): 510.3 [M+H.sup.+].

Example 186: (1R*,2R*)-9-fluoro-4-oxo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylic acid hydrochloride

(1148) A solution of the compound of Example 181 (20 mg) in dioxane (1 mL) was treated with aq. HCl (37%; 0.142 mL) and stirred at 50° C. for 3 h. The solution was concentrated under reduced pressure and the residue was suspended in EA/MeOH (4:1), filtered, washed with TBME and dried in HV, affording a gray solid (6 mg; 29% yield).

(1149) MS (ESI, m/z): 539.2 [M+H.sup.+].

Example 187: (RS)-9-fluoro-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1150) A solution of the compound of Example 2 (60 mg) in MeOH/AcOH (1:1, 2 mL) was hydrogenated over Pd/C (133 mg) overnight. The catalyst was filtered off and thoroughly washed with MeOH and MeOH/DCM. The filtrate was concentrated under reduced pressure. The residue was taken up in water and 28% aq. NH.sub.4OH, filtered, washed with water and TBME and dried under reduced pressure, affording an off-white foam (45 mg; 75% yield).

(1151) MS (ESI, m/z): 481.5 [M+H.sup.+].

Example 188: (1R*,2S*)-2-aminomethyl-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

188. i. (1R*,2S*)-methanesulfonic acid 9-fluoro-4-oxo-1-{3-[2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-2-ylmethyl ester

(1152) Starting from the compounds of Preparations CE and U and using procedure E, the title compound was obtained as an off-white foam (79 mg; 30% yield).

(1153) MS (ESI, m/z): 603.3 [M+H.sup.+].

188. ii. (1R*,2S*)-2-azidomethyl-9-fluoro-1-{3-[2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1154) NaN.sub.3 (25 mg) was added to a solution of intermediate 188.i (77 mg) in DMF (1.5 mL) and the resulting mixture was stirred at 80° C. for 1 h. Water and EA were added and the phases separated. The aq. layer was extracted once more with EA and the combined org. layers were washed with water and brine, dried over MgSO.sub.4 and concentrated. The residue was purified by CC (DCM/MeOH/NH.sub.4OH 1000:50:4), affording a light yellow foam (57 mg; 81% yield).

(1155) MS (ESI, m/z): 550.5 [M+H.sup.+].

188. iii. (1R*,2S*)-2-aminomethyl-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1156) A solution of intermediate 188.ii (57 mg) in THF (1.5 mL) was treated with PPh.sub.3 (30 mg) and water (19 μL). The mixture was heated at 70° C. overnight, concentrated under reduced pressure and the residue was taken in DCM. The DCM layer was extracted with 1M HCl and the aq. layer was basified with NH.sub.4OH. The aq. layer was extracted with DCM/MeOH (9:1) and the combined org. layers were dried over MgSO.sub.4, concentrated and purified by CC (DCM/MeOH/NH.sub.4OH 1000:100:8), affording a light yellow foam (26 mg; 48% yield).

(1157) MS (ESI, m/z): 524.3 [M+H.sup.+].

Example 189: (S)-9-fluoro-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1158) Starting from the compounds of Preparations CF and BJ and using procedure E, the title compound was obtained as an off-white foam (52 mg; 32% yield).

(1159) MS (ESI, m/z): 480.5 [M+H.sup.+].

Example 190: (S)-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1160) Starting from the compounds of Preparations CF and AR and using procedure E, the title compound was obtained as an off-white foam (64 mg; 34% yield).

(1161) MS (ESI, m/z): 480.5 [M+H.sup.+].

Example 191: (S)-9-fluoro-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-U]quinolin-4-one

(1162) Starting from the compounds of Preparations CF and BL and using procedure E, the title compound was obtained as an off-white foam (53 mg; 27% yield).

Example 192: (S)-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1163) Starting from the compounds of Preparations CF and BK and using procedure E, the title compound was obtained as an off-white solid (73 mg; 38% yield).

(1164) MS (ESI, m/z): 496.6 [M+H.sup.+].

Example 193: (R)-9-fluoro-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1165) Starting from the compounds of Preparations CG and BJ and using procedure E, the title compound was obtained as an off-white foam (56 mg; 34% yield).

(1166) MS (ESI, m/z): 480.6 [M+H.sup.+].

Example 194: (R)-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1167) Starting from the compounds of Preparations CG and AR and using procedure E, the title compound was obtained as an off-white foam (71 mg; 38% yield).

(1168) MS (ESI, m/z): 480.6 [M+H.sup.+].

Example 195: (R)-9-fluoro-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1169) Starting from the compounds of Preparations CG and BL and using procedure E, the title compound was obtained as a light yellow solid (52 mg; 27% yield).

(1170) MS (ESI, m/z): 496.5 [M+H.sup.+].

Example 196: (R)-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1171) Starting from the compounds of Preparations CG and BK and using procedure E, the title compound was obtained as a light yellow solid (55 mg; 28% yield).

(1172) MS (ESI, m/z): 496.6 [M+H.sup.+].

Example 197: (RS)-9-fluoro-1-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1173) Starting from the compounds of Preparations A and CH and using procedure C, the title compound was obtained as a pale yellow solid (40 mg; 22% yield).

(1174) MS (ESI, m/z): 496.6 [M+H.sup.+].

Example 198: (RS)-9-fluoro-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

(1175) Starting from the compounds of Preparations A and BX and using procedure C, the title compound was obtained as a pale yellow solid (10 mg; 11% yield).

(1176) MS (ESI, m/z): 496.4 [M+H.sup.+].

Example 199: (RS)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

(1177) Starting from the compounds of Preparations CI and BK and using procedure E, the title compound was obtained as a light yellow solid (650 mg; 26% yield).

(1178) MS (ESI, m/z): 497.5 [M+H.sup.+].

Example 200: (RS)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2,5,6-tetrahydro-pyrrolo[1,2,3-de]quinoxalin-3-one

(1179) A solution of the compound of Preparation CI (0.2 g, 0.975 mmol) and the compound of Preparation BK (0.3 g, 0.975 mmol) in DCE/MeOH (1:1, 8 mL) was stirred at rt overnight.

(1180) NaBH.sub.4 (110 mg) was added and the mixture stirred at rt for 1 h. The mixture was quenched with HCl 1M and partitioned between DCM and diluted NH.sub.4OH. The org. phase was dried over MgSO.sub.4 and concentrated. The residue was purified by CC (DCM/MeOH 19:1 containing 1% NH.sub.4OH). The title compound was obtained as a light rose foam (78 mg; 16% yield).

(1181) MS (ESI, m/z): 499.5 [M+H.sup.+].

Example 201: (RS)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1-methyl-1,2,5,6-tetrahydro-pyrrolo[1,2,3-de]quinoxalin-3-one dihydrochloride

201.i. ((RS)-7-fluoro-3-oxo-5,6-dihydro-3H-pyrrolo[1,2,3-de]quinoxalin-6-yl)-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-carbamic acid tert-butyl ester

(1182) A suspension of the compound of Example 199 (0.6 g, 1.2 mmol) in DCM (10 mL), MeOH (2 mL) and THF (5 mL) was treated with Boc.sub.2O (526 mg, 2 eq.) was heated at reflux overnight. The volatiles were removed under reduced pressure and the residue purified by CC (EA) to give the desired intermediate as a beige foam (0.61 g, 85% yield).

(1183) MS (ESI, m/z): 597.7 [M+H.sup.+].

201. ii. ((RS)-7-fluoro-3-oxo-2,3,5,6-tetrahydro-1H-pyrrolo[1,2,3-de]quinoxalin-6-yl)-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-carbamic acid tert-butyl ester

(1184) A solution of intermediate 201.i (610 mg) in MeOH/DCM (4:1; 20 mL) was treated with NaBH.sub.4 (77 mg, 2 eq.) and stirred at rt for 2 h. The mixture was quenched with HCl 1M and partitioned between DCM and diluted NH.sub.4OH. The org. phase was dried over MgSO.sub.4 and concentrated. The residue was purified by CC (EA). The title compound was obtained as a beige foam (410 mg; 67% yield).

(1185) MS (ESI, m/z): 599.6 [M+H.sup.+].

201. iii. ((R)-7-fluoro-1-methyl-3-oxo-2,3,5,6-tetrahydro-1H-pyrrolo[1,2,3-de]quinoxalin-6-yl)-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-carbamic acid tert-butyl ester

(1186) A solution of intermediate 201.ii (100 mg) in MeOH (3 mL) was treated with AcOH (0.019 mL), aq. formaldehyde (37%, 0.026 mL) and NaCNBH.sub.3 (30 mg). The mixture was stirred at rt for 3 h. The mixture was diluted with EA and water and the org. phase was washed with NaHCO.sub.3 and brine, dried over MgSO.sub.4 and concentrated. The residue was crystallized from ether to give the desired intermediate as a colourless solid (0.075 g, 73% yield).

(1187) MS (ESI, m/z): 613.7 [M+H.sup.+].

201. iv. (RS)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1-methyl-1, 2,5,6-tetrahydro-pyrrolo[1, 2,3-de]quinoxalin-3-one dihydrochloride

(1188) A suspension of intermediate 201.iii (0.068 g, 0.1 mmol) in HCl (4M in dioxane, 1 mL) was stirred at rt for 15 min. The volatiles were removed under reduced pressure and the solid was washed with ether and dried at HV. The title salt was isolated as a grey solid (0.068 g; quant.).

(1189) MS (ESI, m/z): 513.6 [M+H.sup.+].

Example 202: (RS)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1-(3-hydroxypropyl)-1,2,5,6-tetrahydro-pyrrolo[1,2,3-de]quinoxalin-3-one dihydrochloride

202.i. ((R)-7-fluoro-1-(3-hydroxypropyl)-methyl-3-oxo-2, 3,5,6-tetrahydro-1H-pyrrolo[1,2,3-de]quinoxalin-6-yl)-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-carbamic acid tert-butyl ester

(1190) A solution of intermediate 201.ii (100 mg) in MeOH (3 mL) was treated with AcOH (0.019 mL), aq. formaldehyde (37%, 0.026 mL) and 3-[(tert-butyldimethylsilyl)oxy]-1-propanal (88 mg, commercial). The mixture was stirred at rt for 5 h. The mixture was diluted with EA and water and the org. phase was washed with NaHCO.sub.3 and brine, dried over MgSO.sub.4 and concentrated. The residue was purified by CC (EA) to give the desired intermediate as a yellowish oil (0.11 g, 62% yield).

(1191) MS (ESI, m/z): 771.6 [M+H.sup.+].

202. ii. (RS)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1-(3-hydroxypropyl)-1, 2,5,6-tetrahydro-pyrrolo[1,2,3-de]quinoxalin-3-one dihydrochloride

(1192) A suspension of intermediate 202.i (0.11 g, 0.14 mmol) in HCl (4M in dioxane, 1.5 mL) was stirred at rt for 15 min. The volatiles were removed under reduced pressure and the solid was washed with ether and dried at HV. The title salt was isolated as a grey solid (0.071 g; 78% yield).

(1193) MS (ESI, m/z): 557.3 [M+H.sup.+].

Pharmacological Properties of the Invention Compounds

In Vitro Assays

Experimental Methods

(1194) Minimal inhibitory concentrations (MICs; mg/1) were determined in cation-adjusted Mueller-Hinton Broth by a microdilution method following the description given in “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically”, Approved standard, 7.sup.th ed., Clinical and Laboratory Standards Institute (CLSI) Document M7-A7, Wayne, Pa., USA, 2006.

(1195) Results:

(1196) All Example compounds were tested against several Gram positive and Gram negative bacteria such as S. aureus, E. faecalis, S. pneumoniae, M catarrhalis, A. baumanii, E. coli or P. aeruginosa.

(1197) Typical antibacterial test results are given in the table hereafter (MIC in mg/l).

(1198) TABLE-US-00001 MIC for MIC for Example No. M. catarrhalis A894 Example No. M. catarrhalis A894 1 ≦0.031 2 ≦0.031 3 ≦0.031 4 ≦0.031 5 ≦0.031 6 0.125 7 ≦0.031 8 ≦0.031 9 ≦0.031 10 ≦0.031 11 0.063 12 ≦0.031 13 ≦0.031 14 ≦0.031 15 ≦0.031 16 ≦0.031 17 ≦0.031 18 ≦0.031 19 ≦0.031 20 ≦0.031 21 ≦0.031 22 ≦0.031 23 ≦0.031 24 ≦0.031 25 ≦0.031 26 0.25 27 0.5 28 ≦0.031 29 ≦0.031 30 0.031 31 16 32 0.031 33 16 34 ≦0.031 35 ≦0.031 36 8 37 1 38 16 39 ≦0.031 40 0.125 41 0.5 42 2 43 1 44 0.125 45 0.063 46 ≦0.031 47 ≦0.031 48 ≦0.031 49 ≦0.031 50 ≦0.031 51 ≦0.031 52 ≦0.031 53 ≦0.031 54 0.25 55 ≦0.031 56 ≦0.031 57 ≦0.031 58 ≦0.031 59 4 60 ≦0.031 61 ≦0.031 62 ≦0.031 63 0.031 64 ≦0.031 65 ≦0.031 66 ≦0.031 67 ≦0.063 68 ≦0.031 69 ≦0.031 70 ≦0.031 71 ≦0.031 72 ≦0.031 73 ≦0.031 74 ≦0.031 75 ≦0.031 76 ≦0.031 77 0.031 78 ≦0.031 79 ≦0.031 80 ≦0.031 81 ≦0.031 82 0.25 83 ≦0.031 84 0.063 85 ≦0.031 86 ≦0.031 87 ≦0.031 88 ≦0.031 89 0.063 90 ≦0.031 91 ≦0.031 92 ≦0.031 93 ≦0.031 94 ≦0.031 95 ≦0.031 96 ≦0.031 97 ≦0.031 98 0.25 99 ≦0.031 100 0.031 101 ≦0.031 102 ≦0.031 103 ≦0.031 104 ≦0.031 105 ≦0.031 106 ≦0.031 107 8 108 ≦0.031 109 ≦0.031 110 ≦0.031 111 0.125 112 ≦0.031 113 ≦0.031 114 ≦0.031 115 ≦0.031 116 ≦0.031 117 ≦0.031 118 ≦0.031 119 ≦0.031 120 0.125 121 0.125 122 0.5 123 0.125 124 ≦0.031 125 ≦0.031 126 ≦0.031 127 ≦0.031 128 ≦0.031 129 ≦0.031 130 ≦0.031 131 ≦0.031 132 ≦0.031 133 ≦0.031 134 ≦0.031 135 ≦0.031 136 ≦0.031 137 ≦0.031 138 ≦0.031 139 ≦0.031 140 ≦0.031 141 ≦0.031 142 ≦0.031 143 ≦0.031 144 ≦0.031 145 ≦0.031 146 ≦0.031 147 ≦0.031 148 ≦0.031 149 ≦0.031 150 ≦0.031 151 ≦0.031 152 ≦0.031 153 ≦0.031 154 ≦0.031 155 ≦0.031 156 ≦0.031 157 2 158 ≦0.031 159 ≦0.031 160 ≦0.031 161 0.125 162 0.25 163 0.031 164 0.031 165 0.125 166 ≦0.031 167 ≦0.031 168 ≦0.031 169 ≦0.031 170 0.25 171 ≦0.031 172 0.25 173 0.125 174 ≦0.031 175 ≦0.031 176 ≦0.031 177 ≦0.031 178 ≦0.031 179 ≦0.031 180 ≦0.031 181 ≦0.031 182 ≦0.031 183 ≦0.031 184 ≦0.031 185 ≦0.031 186 0.5 187 ≦0.031 188 ≦0.031 189 ≦0.031 190 ≦0.031 191 ≦0.031 192 ≦0.031 193 ≦0.031 194 ≦0.031 195 ≦0.031 196 ≦0.031 197 ≦0.031 198 ≦0.031 199 ≦0.031 200 ≦0.031 201 ≦0.031 202 0.063

Tricyclic oxazolidinone antibiotic compounds

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A61P31/04

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C07D471/16

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C07D471/06

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A61P31/00

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C07D487/06

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C07D519/00

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International classification

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A61K31/54

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C07D471/16

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C07D471/06

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C07D519/00

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A61K31/535

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C07D487/06

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Abstract

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