PROCESS FOR PREPARING 4-AMINO-PYRIDAZINES

Abstract

Provided herein is a process for preparing a pyridazine amine compound of formula V, and a process for preparing dichloropyridazine amine compounds of formula IVa, IVb, and mixtures thereof. Further, provided herein are dichloropyridazine amine compounds of formula IVa, IVb, and mixtures thereof, wherein the amino group is an ethylamino group.

Claims

1. A process for preparing a pyridazine amine compound of formula V or a salt, tautomer, or N-oxide thereof ##STR00054## comprising the step of reacting (a) a dichloropyridazine amine compound of formula IVa or a salt, tautomer, or N-oxide thereof, or (b) a dichloropyridazine amine compound of formula IVb or a salt, tautomer or N-oxide thereof, or (c) a mixture of (a) and (b) ##STR00055## with hydrogen in the presence of a hydrogenation catalyst, wherein R.sup.1 is CH.sub.2CH.sub.3.

2. The process according to claim 1, wherein the reaction is performed in the absence of a HCl scavenger.

3. The process according to claim 1, wherein an HCl scavenger is added after removal of the hydrogenation catalyst, and wherein the HCl scavenger is provided without water.

4. The process according to claim 3, wherein the HCl scavenger is selected from the group consisting of bases including alkali metal and alkaline earth metal hydroxides, alkali metal and alkaline earth metal oxides, alkali metal and alkaline earth metal hydrides, alkali metal amides, alkali metal and alkaline earth metal carbonates, alkali metal bicarbonates, alkali metal alkyls, alkylmagnesium halides, alkali metal and alkaline earth metal alcoholates, nitrogen containing bases including tertiary amines, pyridines, bicyclic amines, ammonia, and primary amines, and combinations thereof; buffers including sodium acetate and/or ammonium formate; precursors of ionic liquids including imidazoles; and combinations thereof.

5. The process according to claim 1, wherein the hydrogenation catalyst is selected from the group consisting of platinum or palladium on a carrier, Raney nickel, and Raney cobalt, and is preferably platinum or palladium on carbon.

6. (canceled)

7. The process according to claim 1, wherein the process further comprises the step of preparing (a) the dichloropyridazine amine compound of formula IVa or a salt, tautomer, or N-oxide thereof, or (b) the dichloropyridazine amine compound of formula IVb or a salt, tautomer, or N-oxide thereof, or (c) the mixture of (a) and (b) ##STR00056## in a one-pot reaction comprising the steps of reacting a compound of formula II ##STR00057## with POCl.sub.3, and reacting a resulting crude reaction product with an amine compound R.sup.1—NH.sub.2 or a salt thereof, wherein R.sup.1 is as defined in claim 1.

8. The process according to claim 1, wherein the process further comprises the step of preparing (a) the dichloropyridazine amine compound of formula IVa or a salt, tautomer, or N-oxide thereof, or (b) the dichloropyridazine amine compound of formula IVb or a salt, tautomer, or N-oxide thereof, or (c) the mixture of (a) and (b) ##STR00058## by reacting a trichloropyridazine compound of formula III ##STR00059## with an amine compound R.sup.1—NH.sub.2 or a salt thereof, wherein R.sup.1 is as defined in claim 1, and wherein the process optionally further comprises the step of preparing the trichloropyridazine compound of formula III ##STR00060## by reacting a compound of formula II ##STR00061## with POCl.sub.3.

9. The process according to claim 7, wherein the process further comprises the step of preparing the compound of formula II ##STR00062## by reacting mucochloric acid (I) ##STR00063## with hydrazine or a salt thereof.

10. The process according to claim 1, wherein the process further comprises the step of converting the pyridazine amine compound of formula V or a salt, tautomer, or N-oxide thereof into a compound of formula VII or a stereoisomer, salt, tautomer, or N-oxide thereof ##STR00064## by reacting the pyridazine amine compound of formula V or a salt, tautomer, or N-oxide thereof ##STR00065## with a compound of formula VI or a stereoisomer, salt, tautomer, or N-oxide thereof ##STR00066## wherein R.sup.1 is as defined in claim 1; and wherein R.sup.2 is H, halogen, CN, NO.sub.2, C.sub.1-C.sub.10-alkyl, C.sub.2-C.sub.10-alkenyl, or C.sub.2-C.sub.10-alkynyl, wherein the 3 last mentioned radicals may be unsubstituted, may be partially or fully halogenated or may carry 1, 2 or 3 identical or different substituents R.sup.x, or OR.sup.a, SR.sup.a, C(Y)R.sup.b, C(Y)OR.sup.c, S(O)R.sup.d, S(O).sub.2R.sup.d, NR.sup.eR.sup.f, C(Y)NR.sup.gR.sup.h, heterocyclyl, hetaryl, C.sub.3-C.sub.10-cycloalkyl, C.sub.3-C.sub.10-cycloalkenyl or phenyl, wherein the five last mentioned radicals may be unsubstituted or may carry 1, 2, 3, 4 or 5 identical or different substituents selected from the radicals R.sup.y and R.sup.x; R.sup.3 is H, halogen, CN, NO.sub.2, C.sub.1-C.sub.10-alkyl, C.sub.2-C.sub.10-alkenyl, or C.sub.2-C.sub.10-alkynyl, wherein the 3 last mentioned radicals may be unsubstituted, may be partially or fully halogenated or may carry 1, 2 or 3 identical or different substituents R.sup.x, or OR.sup.a, SR.sup.a, C(Y)R.sup.b, C(Y)OR.sup.c, S(O)R.sup.d, S(O).sub.2R.sup.d, NR.sup.eR.sup.f, C(Y)NR.sup.gR.sup.h, heterocyclyl, hetaryl, C.sub.3-C.sub.10-cycloalkyl, C.sub.3-C.sub.10-cycloalkenyl or phenyl, wherein the five last mentioned radicals may be unsubstituted or may carry 1, 2, 3, 4 or 5 identical or different substituents selected from the radicals R.sup.y and R.sup.x; R.sup.N is H, CN, NO.sub.2, C.sub.1-C.sub.10-alkyl, C.sub.2-C.sub.10-alkenyl, or C.sub.2-C.sub.10-alkynyl, wherein the three last mentioned radicals may be unsubstituted, may be partially or fully halogenated or may carry 1, 2 or 3 identical or different substituents R.sup.x, or OR.sup.a, SR.sup.a, C(Y)R.sup.b, C(Y)OR.sup.c, S(O)R.sup.d, S(O).sub.2R.sup.d, NR.sup.eR.sup.f, C(Y)NR.sup.gR.sup.h, S(O).sub.mNR.sup.eR.sup.f, C(Y)NR′NR.sup.eR.sup.f, C.sub.1-C.sub.5-alkylen-OR.sup.3, C.sub.1-C.sub.5-alkylen-CN, C.sub.1-C.sub.5-alkylen-C(Y)R.sup.b, C.sub.1-C.sub.5-alkylen-C(Y)OR.sup.c, C.sub.1-C.sub.5-alkylen-NR.sup.eR.sup.f, C.sub.1-C.sub.5-alkylen-C(Y)NR.sup.gR.sup.h, C.sub.1-C.sub.5-alkylen-S(O).sub.mR.sup.d, C.sub.1-C.sub.5-alkylen-S(O).sub.mNR.sup.eR.sup.f, C.sub.1-C.sub.5-alkylen-NR′NR.sup.eR.sup.f, heterocyclyl, hetaryl, C.sub.3-C.sub.10-cycloalkyl, C.sub.3-C.sub.10-cycloalkenyl, heterocyclyl-C.sub.1-C.sub.5-alkyl, hetaryl-C.sub.1-C.sub.5-alkyl, C.sub.3-C.sub.10-cycloalkyl-C.sub.1-C.sub.5-alkyl, C.sub.3-C.sub.10-cycloalkenyl-C.sub.1-C.sub.5-alkyl, phenyl-C.sub.1-C.sub.5-alkyl, or phenyl, wherein the rings of the ten last mentioned radicals may be unsubstituted or may carry 1, 2, 3, 4 or 5 identical or different substituents R.sup.y; and wherein R.sup.a, R.sup.b, R.sup.c are independently of each other selected from H, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-cycloalkylmethyl, C.sub.3-C.sub.6-halocycloalkyl, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-haloalkenyl, C.sub.2-C.sub.4-alkynyl, C.sub.1-C.sub.4-alkoxy-C.sub.1-C.sub.4-alkyl, heterocyclyl, heterocyclyl-C.sub.1-C.sub.4-alkyl, phenyl, hetaryl, phenyl-C.sub.1-C.sub.4-alkyl, and hetaryl-C.sub.1-C.sub.4-alkyl, wherein the ring in the six last mentioned radicals may be unsubstituted or may carry 1, 2, 3, 4, or 5 substituents which, independently of each other, are selected from halogen, CN, NO.sub.2, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy, and C.sub.1-C.sub.4-haloalkoxy; R.sup.d is selected from C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-cycloalkylmethyl, C.sub.3-C.sub.6-halocycloalkyl, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-haloalkenyl, C.sub.2-C.sub.4-alkynyl, C.sub.1-C.sub.4-alkoxy-C.sub.1-C.sub.4-alkyl, heterocyclyl, heterocyclyl-C.sub.1-C.sub.4-alkyl, phenyl, hetaryl, phenyl-C.sub.1-C.sub.4-alkyl, and hetaryl-C.sub.1-C.sub.4-alkyl, wherein the ring in the six last mentioned radicals may be unsubstituted or may carry 1, 2, 3, 4, or 5 substituents which are independently of each other selected from halogen, CN, NO.sub.2, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy, and C.sub.1-C.sub.4-haloalkoxy; R.sup.e, R.sup.f are independently of each other selected from H, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-cycloalkylmethyl, C.sub.3-C.sub.6-halocycloalkyl, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-haloalkenyl, C.sub.2-C.sub.4-alkynyl, C.sub.1-C.sub.4-alkoxy-C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-alkylcarbonyl, C.sub.1-C.sub.4-haloalkylcarbonyl, C.sub.1-C.sub.4-alkylsulfonyl, C.sub.1-C.sub.4-haloalkylsulfonyl, heterocyclyl, heterocyclyl-C.sub.1-C.sub.4-alkyl, heterocyclylcarbonyl, heterocyclylsulfonyl, phenyl, phenylcarbonyl, phenylsulfonyl, hetaryl, hetarylcarbonyl, hetarylsulfonyl, phenyl-C.sub.1-C.sub.4-alkyl, and hetaryl-C.sub.1-C.sub.4-alkyl, wherein the ring in the twelve last mentioned radicals may be unsubstituted or may carry 1, 2, 3, 4, or 5 substituents which, independently of each other, are selected from halogen, CN, NO.sub.2, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy, and C.sub.1-C.sub.4-haloalkoxy; or R.sup.e and R.sup.f together with the nitrogen atom to which they are bound form a 5- or 6-membered, saturated or unsaturated heterocycle, which may carry a further heteroatom being selected from O, S and N as a ring member atom and wherein the heterocycle may be unsubstituted or may carry 1, 2, 3, 4, or 5 substituents which are independently of each other selected from halogen, CN, NO.sub.2, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy, and C.sub.1-C.sub.4-haloalkoxy; R.sup.g, R.sup.h are independently of each other selected from H, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-halocycloalkyl, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-haloalkenyl, C.sub.2-C.sub.4-alkynyl, C.sub.1-C.sub.4-alkoxy-C.sub.1-C.sub.4-alkyl, heterocyclyl, heterocyclyl-C.sub.1-C.sub.4-alkyl, phenyl, hetaryl, phenyl-C.sub.1-C.sub.4-alkyl, and hetaryl-C.sub.1-C.sub.4-alkyl, wherein the ring in the six last mentioned radicals may be unsubstituted or may carry 1, 2, 3, 4, or 5 substituents which are independently of each other selected from halogen, CN, NO.sub.2, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy, and C.sub.1-C.sub.4-haloalkoxy; R.sup.i is selected from H, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-cycloalkylmethyl, C.sub.3-C.sub.6-halocycloalkyl, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-haloalkenyl, C.sub.2-C.sub.4-alkynyl, C.sub.1-C.sub.4-alkoxy-C.sub.1-C.sub.4-alkyl, phenyl, and phenyl-C.sub.1-C.sub.4-alkyl, wherein the phenyl ring in the two last mentioned radicals may be unsubstituted or may carry 1, 2, 3, 4, or 5 substituents which are independently of each other selected from halogen, CN, NO.sub.2, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy, and C.sub.1-C.sub.4-haloalkoxy; R.sup.x is selected from CN, NO.sub.2, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy, S(O).sub.mR.sup.d, S(O).sub.mNR.sup.eR.sup.f, C.sub.1-C.sub.10-alkylcarbonyl, C.sub.1-C.sub.4-haloalkylcarbonyl, C.sub.1-C.sub.4-alkoxycarbonyl, C.sub.1-C.sub.4-haloalkoxycarbonyl, C.sub.3-C.sub.6-cycloalkyl, 5- to 7-membered heterocyclyl, 5- or 6-membered hetaryl, phenyl, C.sub.3-C.sub.6-cycloalkoxy, 3- to 6-membered heterocyclyloxy, and phenoxy, wherein the last 7 mentioned radicals may be unsubstituted or may carry 1, 2, 3, 4, or 5 radicals R.sup.y; R.sup.y is selected from halogen, CN, NO.sub.2, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy, S(O).sub.mR.sup.d, S(O).sub.mNR.sup.eR.sup.f, C.sub.1-C.sub.4-alkylcarbonyl, C.sub.1-C.sub.4-haloalkylcarbonyl, C.sub.1-C.sub.4-alkoxycarbonyl, C.sub.1-C.sub.4-haloalkoxycarbonyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-halocycloalkyl, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-haloalkenyl, C.sub.2-C.sub.4-alkynyl, and C.sub.1-C.sub.4-alkoxy-C.sub.1-C.sub.4-alkyl; and wherein Y is O or S; and m is 0, 1 or 2; and wherein X.sup.1 is a leaving group.

11. The process according to claim 10, wherein R.sup.2 is C.sub.1-C.sub.4-alkyl, which may be unsubstituted, or may be partially or fully halogenated; R.sup.3 is H; and wherein R.sup.N is a group —CR.sup.4R.sup.5R.sup.6 wherein R.sup.4 is selected from C.sub.1-C.sub.4-alkyl, which may be unsubstituted, may be partially or fully halogenated, or may carry 1 or 2 identical or different substituents R.sup.x, wherein R.sup.x is selected from CN and C(O)NH.sub.2, and C.sub.3-C.sub.6-cycloalkyl, which may be unsubstituted or may carry 1, 2, or 3 identical or different substituents R.sup.y, wherein R.sup.y is selected from halogen, CN and C(O)NH.sub.2; and R.sup.5 is selected from C.sub.1-C.sub.4-alkyl, which may be unsubstituted, may be partially or fully halogenated, or may carry 1 or 2 identical or different substituents R.sup.x, wherein R.sup.x is selected from CN and C(O)NH.sub.2, and C.sub.3-C.sub.6-cycloalkyl, which may be unsubstituted or may carry 1, 2 or 3 identical or different substituents R.sup.y, wherein R.sup.y is selected from halogen, CN and C(O)NH.sub.2; or R.sup.4 and R.sup.5 together with the carbon atom to which they are attached form a 3- to 12-membered non-aromatic, saturated carbocycle, which may be partially or fully substituted by R.sup.j, wherein R.sup.j is selected from halogen, CN, and C(O)NH.sub.2, and R.sup.6 is H; and wherein X.sup.1 preferably selected from halogen, N.sub.3, p-nitrophenoxy, and pentafluorophenoxy.

12. A process for preparing (a) a dichloropyridazine amine compound of formula IVa or a salt, tautomer, or N-oxide thereof, or (b) a dichloropyridazine amine compound of formula IVb or a salt, tautomer, or N-oxide thereof, or (c) a mixture of (a) and (b) ##STR00067## in a one-pot reaction comprising steps of reacting a compound of formula II ##STR00068## with POCl.sub.3, and reacting the resulting crude reaction product with an amine compound R.sup.1—NH.sub.2 or a salt thereof, wherein R.sup.1 is CH.sub.2CH.sub.3.

13. (canceled)

14. The process according to claim 12, wherein the process further comprises the step of preparing a compound of formula II ##STR00069## by reacting mucochloric acid (I) ##STR00070## with hydrazine and a salt thereof.

15. The process according to claim 12 wherein the process further comprises the step of converting (a) the dichloropyridazine amine compound of formula IVa or a salt, tautomer, or N-oxide thereof, or (b) the dichloropyridazine amine compound of formula IVb or a salt, tautomer, or N-oxide thereof, or (c) the mixture of (a) and (b) into a pyridazine amine compound of formula V or a salt, tautomer, or N-oxide thereof ##STR00071## by reacting (a) the dichloropyridazine amine compound of formula IVa or a salt, tautomer, or N-oxide thereof, or (b) the dichloropyridazine amine compound of formula IVb or a salt, tautomer, or N-oxide thereof, or (c) the mixture of (a) and (b) ##STR00072## with hydrogen in the presence of a hydrogenation catalyst, wherein R.sup.1 is as defined in claim 12; wherein the process optionally further comprises the step of converting the pyridazine amine compound of formula V or a salt, tautomer, or N-oxide thereof into a compound of formula VII or a stereoisomer, salt, tautomer, or N-oxide thereof ##STR00073## by reacting the pyridazine amine compound of formula V or a salt, tautomer, or N-oxide thereof ##STR00074## with a compound of formula VI or a stereoisomer, salt, tautomer, or N-oxide thereof ##STR00075## wherein R.sup.1 is as defined in claim 12; wherein R.sup.2 is H, halogen, CN, NO.sub.2, C.sub.1-C.sub.10-alkyl, C.sub.2-C.sub.10-alkenyl, or C.sub.2-C.sub.10-alkynyl, wherein the 3 last mentioned radicals may be unsubstituted, may be partially or fully halogenated or may carry 1, 2 or 3 identical or different substituents R.sup.x, or OR.sup.a, SR.sup.a, C(Y)R.sup.b, C(Y)OR.sup.c, S(O)R.sup.d, S(O).sub.2R.sup.d, NR.sup.eR.sup.f, C(Y)NR.sup.gR.sup.h, heterocyclyl, hetaryl, C.sub.3-C.sub.10-cycloalkyl, C.sub.3-C.sub.10-cycloalkenyl or phenyl, wherein the five last mentioned radicals may be unsubstituted or may carry 1, 2, 3, 4 or 5 identical or different substituents selected from the radicals R.sup.y and R.sup.x; R.sup.3 is H, halogen, CN, NO.sub.2, C.sub.1-C.sub.10-alkyl, C.sub.2-C.sub.10-alkenyl, or C.sub.2-C.sub.10-alkynyl, wherein the 3 last mentioned radicals may be unsubstituted, may be partially or fully halogenated or may carry 1, 2 or 3 identical or different substituents R.sup.x, or OR.sup.a, SR.sup.a, C(Y)R.sup.b, C(Y)OR.sup.c, S(O)R.sup.d, S(O).sub.2R.sup.d, NR.sup.eR.sup.f, C(Y)NR.sup.gR.sup.h, heterocyclyl, hetaryl, C.sub.3-C.sub.10-cycloalkyl, C.sub.3-C.sub.10-cycloalkenyl or phenyl, wherein the five last mentioned radicals may be unsubstituted or may carry 1, 2, 3, 4 or 5 identical or different substituents selected from the radicals R.sup.y and R.sup.x; R.sup.N is H, CN, NO.sub.2, C.sub.1-C.sub.10-alkyl, C.sub.2-C.sub.10-alkenyl, or C.sub.2-C.sub.10-alkynyl, wherein the three last mentioned radicals may be unsubstituted, may be partially or fully halogenated or may carry 1, 2 or 3 identical or different substituents R.sup.x, or OR.sup.a, SR.sup.a, C(Y)R.sup.b, C(Y)OR.sup.c, S(O)R.sup.d, S(O).sub.2R.sup.d, NR.sup.eR.sup.f, C(Y)NR.sup.gR.sup.h, S(O).sub.mNR.sup.eR.sup.f, C(Y)NR.sup.iNR.sup.eR.sup.f, C.sub.1-C.sub.5-alkylen-OR.sup.a, C.sub.1-C.sub.5-alkylen-CN, C.sub.1-C.sub.5-alkylen-C(Y)R.sup.b, C.sub.1-C.sub.5-alkylen-C(Y)OR.sup.c, C.sub.1-C.sub.5-alkylen-NR.sup.eR.sup.f, C.sub.1-C.sub.5-alkylen-C(Y)NR.sup.gR.sup.h, C.sub.1-C.sub.5-alkylen-S(O).sub.mR.sup.d, C.sub.1-C.sub.5-alkylen-S(O).sub.mNR.sup.eR.sup.f, C.sub.1-C.sub.5-alkylen-NR.sup.iNR.sup.eR.sup.f, heterocyclyl, hetaryl, C.sub.3-C.sub.10-cycloalkyl, C.sub.3-C.sub.10-cycloalkenyl, heterocyclyl-C.sub.1-C.sub.5-alkyl, hetaryl-C.sub.1-C.sub.5-alkyl, C.sub.3-C.sub.10-cycloalkyl-C.sub.1-C.sub.5-alkyl, C.sub.3-C.sub.10-cycloalkenyl-C.sub.1-C.sub.5-alkyl, phenyl-C.sub.1-C.sub.5-alkyl, or phenyl, wherein the rings of the ten last mentioned radicals may be unsubstituted or may carry 1, 2, 3, 4 or 5 identical or different substituents R.sup.y; and wherein R.sup.a, R.sup.b, R.sup.c are independently of each other selected from H, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-cycloalkylmethyl, C.sub.3-C.sub.6-halocycloalkyl, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-haloalkenyl, C.sub.2-C.sub.4-alkynyl, C.sub.1-C.sub.4-alkoxy-C.sub.1-C.sub.4-alkyl, heterocyclyl, heterocyclyl-C.sub.1-C.sub.4-alkyl, phenyl, hetaryl, phenyl-C.sub.1-C.sub.4-alkyl, and hetaryl-C.sub.1-C.sub.4-alkyl, wherein the ring in the six last mentioned radicals may be unsubstituted or may carry 1, 2, 3, 4, or 5 substituents which, independently of each other, are selected from halogen, CN, NO.sub.2, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy, and C.sub.1-C.sub.4-haloalkoxy; R.sup.d is selected from C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-cycloalkylmethyl, C.sub.3-C.sub.6-halocycloalkyl, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-haloalkenyl, C.sub.2-C.sub.4-alkynyl, C.sub.1-C.sub.4-alkoxy-C.sub.1-C.sub.4-alkyl, heterocyclyl, heterocyclyl-C.sub.1-C.sub.4-alkyl, phenyl, hetaryl, phenyl-C.sub.1-C.sub.4-alkyl, and hetaryl-C.sub.1-C.sub.4-alkyl, wherein the ring in the six last mentioned radicals may be unsubstituted or may carry 1, 2, 3, 4, or 5 substituents which are independently of each other selected from halogen, CN, NO.sub.2, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy, and C.sub.1-C.sub.4-haloalkoxy; R.sup.e, R.sup.f are independently of each other selected from H, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-cycloalkylmethyl, C.sub.3-C.sub.6-halocycloalkyl, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-haloalkenyl, C.sub.2-C.sub.4-alkynyl, C.sub.1-C.sub.4-alkoxy-C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-alkylcarbonyl, C.sub.1-C.sub.4-haloalkylcarbonyl, C.sub.1-C.sub.4-alkylsulfonyl, C.sub.1-C.sub.4-haloalkylsulfonyl, heterocyclyl, heterocyclyl-C.sub.1-C.sub.4-alkyl, heterocyclylcarbonyl, heterocyclylsulfonyl, phenyl, Phenylcarbonyl, Phenylsulfonyl, hetaryl, hetarylcarbonyl, hetarylsulfonyl, phenyl-C.sub.1-C.sub.4-alkyl, and hetaryl-C.sub.1-C.sub.4-alkyl, wherein the ring in the twelve last mentioned radicals may be unsubstituted or may carry 1, 2, 3, 4, or 5 substituents which, independently of each other, are selected from halogen, CN, NO.sub.2, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy, and C.sub.1-C.sub.4-haloalkoxy; or R.sup.e and R.sup.f together with the nitrogen atom to which they are bound form a 5- or 6-membered, saturated or unsaturated heterocycle, which may carry a further heteroatom being selected from O, S and N as a ring member atom and wherein the heterocycle may be unsubstituted or may carry 1, 2, 3, 4, or 5 substituents which are independently of each other selected from halogen, CN, NO.sub.2, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy, and C.sub.1-C.sub.4-haloalkoxy; R.sup.g, R.sup.h are independently of each other selected from H, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-halocycloalkyl, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-haloalkenyl, C.sub.2-C.sub.4-alkynyl, C.sub.1-C.sub.4-alkoxy-C.sub.1-C.sub.4-alkyl, heterocyclyl, heterocyclyl-C.sub.1-C.sub.4-alkyl, phenyl, hetaryl, phenyl-C.sub.1-C.sub.4-alkyl, and hetaryl-C.sub.1-C.sub.4-alkyl, wherein the ring in the six last mentioned radicals may be unsubstituted or may carry 1, 2, 3, 4, or 5 substituents which are independently of each other selected from halogen, CN, NO.sub.2, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy, and C.sub.1-C.sub.4-haloalkoxy; R.sup.i is selected from H, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-cycloalkylmethyl, C.sub.3-C.sub.6-halocycloalkyl, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-haloalkenyl, C.sub.2-C.sub.4-alkynyl, C.sub.1-C.sub.4-alkoxy-C.sub.1-C.sub.4-alkyl, phenyl, and phenyl-C.sub.1-C.sub.4-alkyl, wherein the phenyl ring in the two last mentioned radicals may be unsubstituted or may carry 1, 2, 3, 4, or 5 substituents which are independently of each other selected from halogen, CN, NO.sub.2, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy, and C.sub.1-C.sub.4-haloalkoxy; R.sup.x is selected from CN, NO.sub.2, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy, S(O).sub.mR.sup.d, S(O).sub.mNR.sup.eR.sup.f, C.sub.1-C.sub.10-alkylcarbonyl, C.sub.1-C.sub.4-haloalkylcarbonyl, C.sub.1-C.sub.4-alkoxycarbonyl, C.sub.1-C.sub.4-haloalkoxycarbonyl, C.sub.3-C.sub.6-cycloalkyl, 5- to 7-membered heterocyclyl, 5- or 6-membered hetaryl, phenyl, C.sub.3-C.sub.6-cycloalkoxy, 3- to 6-membered heterocyclyloxy, and phenoxy, wherein the last 7 mentioned radicals may be unsubstituted or may carry 1, 2, 3, 4, or 5 radicals R.sup.y; R.sup.y is selected from halogen, CN, NO.sub.2, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy, S(O).sub.mR.sup.d, S(O).sub.mNR.sup.eR.sup.f, C.sub.1-C.sub.4-alkylcarbonyl, C.sub.1-C.sub.4-haloalkylcarbonyl, C.sub.1-C.sub.4-alkoxycarbonyl, C.sub.1-C.sub.4-haloalkoxycarbonyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-halocycloalkyl, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-haloalkenyl, C.sub.2-C.sub.4-alkynyl, and C.sub.1-C.sub.4-alkoxy-C.sub.1-C.sub.4-alkyl; and wherein Y is O or S; and m is 0, 1 or 2; and wherein X.sup.1 is a leaving group.

16. (canceled)

17. (canceled)

Description

EXAMPLES

I. Characterization

[0336] The characterization can be done by coupled High Performance Liquid Chromatography/mass spectrometry (HPLC/MS), by NMR or by their melting points.

[0337] HPLC: Agilent Extend 1.8 μm C18 4.6×100 mm; mobile phase: A: water+0.1% H.sub.3PO.sub.4; B: acetonitrile (MeCN)+0.1% H.sub.3PO.sub.4; gradient: 5-95% A in 10 minutes; 0-10 minutes is 5:95 A:B then gradient from 10-10.1 minutes to 95:5 A:B flow: 1.2 ml/min in 10 minutes at 60° C.

TABLE-US-00001 min A B Flow Pressure (bar) 8 5 95 1.2 400 10 5 95 1.2 400 10.1 95 5 1.2 400

[0338] .sup.1H-NMR: The signals are characterized by chemical shift (ppm) vs. tetramethylsilane, by their multiplicity and by their integral (relative number of hydrogen atoms given). The following abbreviations are used to characterize the multiplicity of the signals: m=multiplet, q=quartet, t=triplet, d=doublet and s=singlet.

[0339] Abbreviations used are: h for hour(s), min for minute(s) and room temperature for 20-25° C.

II. Preparation Examples

1. Preparation of a Mixture of 3,4-dichloro-5-ethylaminopyridazine and 3,5-dichloro-4-ethylaminopyridazine in a one-pot procedure starting from 4,5-dichloro-3-hydroxypyridazine

[0340] 200 g of 4,5-dichloro-3-hydroxypyridazine was placed in a reactor at 20° C. under N.sub.2, and POCl.sub.3 (930 g, 5 equiv) was added and the reaction mixture was heated to 100° C. The reaction mixture was further stirred for 1 hour until full conversion was achieved. The excess POCl.sub.3 was removed via distillation. The reaction mixture was dosed into 1200 g H.sub.2O controlling the temperature at 30° C. Butyl acetate (1200 g) was added and the biphasic mixture was stirred for 30 minutes at 30° C. and then the phases were separated. Another portion of butyl acetate (400 g) was used to wash the aqueous phase. The combined organic phases were washed with 10% HCl and then H.sub.2O.

[0341] To the mixture of trichloropyridazine in butyl acetate was added a solution of ethylamine in water with a concentration of 70 wt.-% of ethylamine based on the total weight of the solution (234 g, 3 equiv) at 35° C. The reaction was held at 45° C. for 3 hours (or until full conversion is observed). The phases were separated at 40° C. and the organic phase was washed once with H.sub.2O. The combined aqueous phases were once extracted with butyl acetate. Butyl acetate from the combined organic phases was distilled (15 mbar, 35° C.) to concentrate the reaction mixture. During this process, the product precipitated from solution. The reaction mixture was cooled to 10° C. and the product was filtered off. The mother liquor was next concentrated and the crude material was recrystallized from MTBE to isolate the remainder of the product.

2. Preparation of 4-ethylaminopyridazine

[0342] 600 g (3.09 mol) of a mixture of 3,4-dichloro-5-ethylaminopyridazine and 3,5-dichloro-4-ethylaminopyridazine was dissolved in EtOH (3.5 liters). 15 g (0.01 mol) of 10% Pd/C was added and the pressure reactor was purged with nitrogen. The pressure reactor was pressurized to 0.2 bar with H.sub.2 and heated to 35° C. As the reaction is exothermic, the temperature was controlled at 55° C. for 4 hours. Afterwards, the pressure was released and the reactor was purged with N.sub.2. The reaction mixture was filtered at room temperature to remove the catalyst. The catalyst can be reused in the next batch without purification.

[0343] In a second reactor, a mixture of K.sub.2CO.sub.3 (1 kg) and 1 liter of EtOH was prepared. The reaction mixture was dosed into the potassium carbonate solution over 60 minutes and the temperature was controlled at 20-25° C. The reaction mixture was further stirred for 3 hours. The salts produced in the process were filtered off. A portion of solvent from the reaction mixture was distilled off and MTBE was added to precipitate out the pure ethylaminopyridazine (354 g, 91% purity, 85% yield).