Method for synthesis of deuterated amide and deuterated sulfonamide

Abstract

A novel method for synthesizing deuterated amides and deuterated sulfonamides includes the following steps: (1) adding a compound M, DMAP, R.sup.3—X to a solvent to obtain a compound N after a reaction is complete; and (2) adding the compound N, R.sup.4—NH—R.sup.5, or a salt and base thereof to a solvent, and purifying after a reaction is complete to obtain a compound I. ##STR00001##

Claims

1. A method for synthesizing deuterated amine, comprising the steps of a first step of adding compound M, DMAP, and R.sup.3—X to a first solvent for reaction to obtain compound N; and a second step of adding compound N, R.sup.4—NH—R.sup.5 or a salt thereof, and a base to a second solvent for reaction to obtain a deuterated amine compound I, ##STR00015## wherein: L is carbonyl or sulfonyl; R.sup.1 is ##STR00016## R.sup.2 is selected from the group consisting of substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclic group, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl; R.sup.3 is —CO—R.sup.6 or —SO2R.sup.7 and X is a leaving group, wherein, R.sup.6 and R.sup.7 are independently selected from alkoxy, alkyl, substituted alkyl, and aryl; R.sup.4 and R.sup.5 are independently selected from H, substituted or unsubstituted deuterated alkyl, deuterated cycloalkyl, deuterated heterocyclic group, deuterated aryl, and deuterated heteroaryl, with the proviso that R.sup.4 and R.sup.5 are not hydrogen at the same time; wherein, in the first step, a yield for the compound N thus synthesized is 92.3%, and wherein, in the second step, a yield for the deuterated amine compound I thus synthesized is 92.8%.

2. The synthetic method according to claim 1, wherein R.sup.3 is selected from —CO—R.sup.6 or —SO2R.sup.7, X is selected from —OR.sup.3, Cl, and Br, wherein R.sup.6 and R.sup.7 are independently selected from t-butoxy, isopropoxy, benzyloxy, methyl, trifluoromethyl, phenyl, and tolyl.

3. The synthetic method according to claim 2, wherein R.sup.6 is selected from t-butoxy, isopropoxy, and benzyloxy, and R.sup.7 is selected from methyl, trifluoromethyl, phenyl, and tolyl.

4. The synthetic method according to claim 3, wherein R.sup.3 is —CO—R.sup.6, X is —OR.sup.3, and R.sup.6 is t-butoxy.

5. The synthetic method according to claim 1, wherein R.sup.4 and R.sup.5 are independently selected from H and deuterated alkyl, with the proviso that R.sup.4 and R.sup.5 are not hydrogen at the same time.

6. The synthetic method according to claim 5, wherein R.sup.4 and R.sup.5 are independently selected from H and deuterated methyl, with the proviso that R.sup.4 and R.sup.5 are not hydrogen at the same time.

7. The synthetic method according to claim 1, wherein R.sup.2 is a substituted or unsubstituted C1-C6 alkyl.

8. The synthetic method according to claim 7, wherein R.sup.2 is a substituted or unsubstituted C1-C4 alkyl.

9. The synthetic method according to claim 8, wherein R.sup.2 is methyl.

10. The synthetic method according to claim 1, wherein compound I is ##STR00017##

11. The synthetic method according to claim 1, wherein in the first step , the first solvent is a polar solvent selected from the group consisting of dichloromethane, dichloroethane, formamide, trifluoroacetic acid, DMSO, acetonitrile, DMF, hexamethylphosphoramide, methanol, ethanol, acetic acid, isopropanol, pyridine, tetramethylethylenediamine, acetone, triethylamine, n-butanol, dioxane, tetrahydrofuran, methyl formate, tributylamine, methyl ethyl ketone, ethyl acetate, chloroform, trioctylamine, dimethyl carbonate, ethyl ether, isopropyl ether, n-butyl ether, trichloroethylene, and diphenyl ether.

12. The synthetic method according to claim 1, wherein in the first step, the first solvent is a non polar solvent selected from the group consisting of benzene, toluene, carbon tetrachloride, carbon disulfide, cyclohexane, and hexane.

13. The synthetic method according to claim 1, wherein, in the first step, a molar ratio of compound M, DMAP, and R.sup.3—X is 1:1-3:1-10.

14. The synthetic method according to claim 1, wherein, in the first step, a ratio of compound M and the first solvent is 1:2-20 mmol/mL.

15. The synthetic method according to claim 1, wherein a reaction temperature of the first step is 10-60° C.

16. The synthetic method according to claim 1, wherein a reaction time of the first step is 10-120 h.

17. The synthetic method according to claim 1, wherein, in the second step, the second solvent is a polar solvent or a non-polar solvent.

18. The synthetic method according to claim 17, wherein said polar solvent is selected from the group consisting of dichloromethane, dichloroethane, formamide, trifluoroacetic acid, DMSO, acetonitrile, DMF, hexamethylphosphoramide, methanol, ethanol, acetic acid, isopropanol, pyridine, tetramethylethylenediamine, acetone, triethylamine, n-butanol, dioxane, tetrahydrofuran, methyl formate, tributylamine, methyl ethyl ketone, ethyl acetate, chloroform, trioctylamine, dimethyl carbonate, ethyl ether, isopropyl ether, n-butyl ether, trichloroethylene, and diphenyl ether.

19. The synthetic method according to claim 17, wherein said non polar solvent is selected from the group consisting of benzene, toluene, carbon tetrachloride, carbon disulfide, cyclohexane, and hexane.

20. The synthetic method according to claim 1, wherein, in the second step, a ratio of compound N and the second solvent is 1:1-25 mmol/mL.

21. The synthetic method according to claim 1, wherein, in the second step, said base is an organic base selected from the group consisting of DBU, sodium methoxide, potassium ethoxide, potassium t-butoxide, sodium t-butoxide, triethylamine, triethylenediamine, DBN, DMAP, pyridine, N-methylmorpholine, tetramethylethylenediamine, TMG, n-butyl lithium, and LDA.

22. The synthetic method according to claim 1, wherein, in the second step, said base is an inorganic base selected from the group consisting of potassium hydroxide, barium hydroxide, calcium hydroxide, aluminum hydroxide, lithium hydroxide, magnesium hydroxide, zinc hydroxide, copper hydroxide, iron hydroxide, lead hydroxide, cobalt hydroxide, chromium hydroxide, zirconium hydroxide, nickel hydroxide, ammonium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, and potassium bicarbonate.

23. The synthetic method according to claim 1, wherein, in the second step, a molar ratio of compound N, R.sup.4—NH—R.sup.5 or its salt, and base is 1:1-4:1-5.

24. The synthetic method according to claim 23, wherein the molar ratio of compound N, R.sup.4—NH—R.sup.5 or its salt, and base is 1:3:4.

25. The synthetic method according to claim 1, wherein a reaction temperature of the second step is 10-100° C.

26. The synthetic method according to claim 1, wherein a reaction time of the second step is 10-120 h.

Description

EXAMPLES

(1) The starting materials and equipment used in the specific examples of the present invention are all known products and can be obtained by purchasing commercially available products.

Example 1 Synthesis of Compound 1

(2) ##STR00007##

(1) t-Butyl (4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioimidazolidin-1-yl)-2-fluorophenyl)(methyl)formamide (1-2)

(3) (4-(3-(4-Cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioimidazolidin-1-yl)-2-fluoro-N-methylbenzamide (1-1, 400 mg, 0.85 mmol) and DMAP (210 mg, 1.7 mmol) were added to 5 mL CH.sub.2Cl.sub.2, to which was added Boc anhydride (280 mg, 1.3 mmol). The reactions were stirred at room temperature overnight. After addition of DCM and 0.1 mol/L dilute HCl (50 mL:50 mL), the mixtures were extracted, and the organic layer was washed with saturated brine twice, dried, rotatory evaporated, and purified by silica gel column to obtain white solid t-butyl (4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioimidazolidin-1-yl)-2-fluorophenyl)(methyl)formamide (1-2, 450 mg, 0.80 mmol), with a yield of 92.3%.

(4) MS (ESI) m/z 465.1 (M-100+1).sup.+.

(2) (4-(3-(4-Cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioimidazolidin-1-yl)-2-fluoro-N-(deuterated methyl)benzamide (1)

(5) t-Butyl (4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioimidazolidin-1-yl)-2-fluorophenyl)(methyl)formamide (1-2, 50 mg, 0.09 mmol) and deuterated methylamine hydrochloride (19 mg, 0.27 mmol) were added to 0.25 mL acetonitrile. White insoluble materials appeared, and DBU (54 mg, 0.36 mmol) was also added, then the solid was dissolved. The resultant mixture was stirred overnight at room temperature, and the sample spot was absorbed on the plate. After developed, the result indicated that the raw material dots disappeared. After addition of DCM and 0.1 mol/L dilute HCl (30 mL:30 mL), the mixtures were extracted, and the organic layer was washed with saturated brine twice, dried, rotatory evaporated, and purified by Pre-TLC to obtain white solid (4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioimidazolidin-1-yl)-2-fluoro-N-(deuterated methyl)benzamide (1, 38 mg, 0.09 mmol), with a yield of 92.8%.

(6) MS (ESI) m/z 468.1 (M+H).sup.+.

(7) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 8.52-8.38 (m, 2H), 8.31 (d, J=1.5 Hz, 1H), 8.10 (dd, J=8.3, 1.7 Hz, 1H), 7.80 (t, J=8.1 Hz, 1H), 7.45 (dd, J=10.7, 1.7 Hz, 1H), 7.35 (dd, J=8.2, 1.8 Hz, 1H), 1.55 (s, 6H).

Example 2 Synthesis of Compound 2

(8) ##STR00008##

(1) 4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thiol-5,7-diazaspiro[3.4]octan-5-yl)-2-fluoro-N-Boc-methylbenzamide (2-2)

(9) 4-(7-(6-Cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thiol-5,7-diazaspiro[3.4]octan-5-yl)-2-fluor o-N-methylbenzamide (2-1, 500.0 mg, 1.05 mmol) and DMAP (384.0 mg, 3.15 mmol) were added to 10 mL CH.sub.2Cl.sub.2, to which was drop added Boc anhydride (458.0 mg, 1.05 mmol). The reactions were stirred overnight at room temperature. After addition of DCM and 0.1 N dilute HCl (50 mL: 50 mL), the mixtures were extracted, and the organic layer was washed with saturated brine twice, dried, rotatory evaporated, and purified by silica gel column to obtain white solid 4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thiol-5,7-diazaspiro[3.4]octan-5-yl)-2-fluoro-N-Boc-methylbenzamide (2-2, 450.0 mg, 0.80 mmol), with a yield of 82.6%.

(10) MS (ESI) m/z 478.0 (M-100+1).sup.+.

(11) (2) 4-(7-(6-Cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thiol-5,7-diazaspiro[3.4]octan-5-yl)-2-fluoro-N-(deuterated methyl)benzamide (2)

(12) 4-(7-(6-Cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thiol-5,7-diazaspiro[3.4]octan-5-yl)-2-fluor o-N-Boc-methylbenzamide (2-2, 200.0 mg, 0.35 mmol) was dissolved in 5 mL acetonitrile, to which was added deuterated methylamine hydrochloride (75.0 mg, 1.06 mmol). Insoluble solid appeared, and DBU (215.6 mg, 1.42 mmol) was added, then the solution became clear. The resultant mixture reacted overnight at room temperature. After addition of CH.sub.2Cl.sub.2 and 0.1 N dilute HCl (30 mL:30 mL), the mixture was extracted, and the organic layer was washed with saturated brine twice, dried, rotatory evaporated, and purified by Pre-TLC to obtain white solid 4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thiol-5,7-diazaspiro[3.4]octan-5-yl)-2-fluor o-N-(deuterated methyl)benzamide (2, 130.0 mg, 0.27 mmol), with a yield of 76.2%.

(13) MS (ESI) m/z 481.0 (M+H).sup.+.

(14) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 9.09 (d, J=2.1 Hz, 1H), 8.43-8.27 (m, 2H), 7.28 (d, J=1.9 Hz, 1H), 7.17 (dd, J=11.5, 1.8 Hz, 1H), 6.71 (d, J=11.6 Hz, 1H), 2.77-2.69 (m, 3H), 2.57 (dt, J=12.7, 10.2 Hz, 2H), 2.32-2.22 (m, 1H).

Example 3 Synthesis of Compound 3

(15) ##STR00009##

(16) (1) Axitinib (3-1, 193 mg, 0.5 mmol, 1.0 eq) was dissolved in CH.sub.2Cl.sub.2 (10 mL), to which was added DMAP (183 mg, 1.5 mmol) under stirring, followed by addition of Boc anhydride (327 mg, 1.5 mmol). The resultant mixture was allowed to react 16 h at room temperature, till the reaction was completed by TLC detection. The reaction system was washed with 0.1 N HCl aqueous solution until DMAP was cleaned off. The organic layer was washed with saturated NaHCO.sub.3 aqueous solution and NaCl aqueous solution, respectively, then dried with anhydrous Na.sub.2SO.sub.4, rotatory evaporated, and purified by thin-layer column chromatography (PE/EA=2:1), to obtain white solid product 6-((2-((t-butoxycarbonyl)(methyl)carbamoyl)phenyl)thio)-3-(2-(pyridin-2-yl)ethylenyl-1H-indazol-1-carboxylic acid (E)-t-butyl ester (3-2), with a yield of 81.9%.

(17) .sup.1H NMR (400 MHz, CDCl3) δ 8.65 (d, J=4.0 Hz, 1H), 8.02 (s, 1H), 7.93 (t, J=10.6 Hz, 2H), 7.77 (d, J=15.6 Hz, 2H), 7.51 (d, J=6.5 Hz, 1H), 7.46-7.41 (m, 1H), 7.39-7.32 (m, 3H), 7.28 (dd, J=8.5, 1.5 Hz, 2H), 3.26 (s, 3H), 1.62 (s, 9H), 1.22 (s, 9H).

(18) (2) Previous product 6-((2-((t-butoxycarbonyl)(methyl)carbamoyl)phenyl)thio)-3-(2-(pyridin-2-yl) ethylenyl-1H-indazol-1-carboxylic acid (E)-t-butyl ester (3-2, 117.2 mg, 0.2 mmol) was dissolved in 5 mL acetonitrile, to which was added deuterated methylamine hydrochloride (56 mg, 0.8 mmol), followed by addition of DBU (136 mg, 0.92 mmol). The resultant mixture reacted overnight at room temperature. The reaction was completed by TLC detection. The resultant mixture was washed with water and extracted with ethyl acetate. The organic layer was successively washed with 0.1 N HCl aqueous solution, saturated NaHCO.sub.3 aqueous solution and NaCl aqueous solution, respectively, and then dried with anhydrous Na.sub.2SO.sub.4, rotatory evaporated, to obtain yellowish solid product (E)-N-(deuterated methyl)-2-(3-(2-(2-pyridinyl)ethylenyl)-1H-indazol-6-yl)thioamide) (3, 75 mg), with a yield of 96.4%.

(19) MS (ESI) m/z 390 (M+H).sup.+.

(20) .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 13.36 (s, 1H), 8.61 (d, J=3.8 Hz, 1H), 8.42-8.35 (m, 1H), 8.22 (d, J=8.5 Hz, 1H), 7.95 (d, J=16.4 Hz, 1H), 7.81 (td, J=7.7, 1.8 Hz, 1H), 7.67 (d, J=7.8 Hz, 1H), 7.63-7.54 (m, 2H), 7.49 (dd, J=7.3, 1.7 Hz, 1H), 7.33-7.25 (m, 3H), 7.19 (dd, J=8.5, 1.1 Hz, 1H), 7.03 (dd, J=7.7, 1.1 Hz, 1H).

Example 4 Synthesis of Compound 4

(21) ##STR00010##

(22) (1) N-methylbenzamide (4-1, 135 mg, 1 mmol) was dissolved in CH.sub.2Cl.sub.2 (5 mL), to which was added DMAP (244 mg, 2 mmol) under stirring, followed by addition of Boc anhydride (436 mg, 2 mmol). The resultant mixture was allowed to react 16 h at room temperature, till the reaction was completed by TLC detection. The reaction system was washed with 0.1 N HCl aqueous solution until DMAP was cleaned off. The organic layer was washed with saturated NaHCO.sub.3 aqueous solution and NaCl aqueous solution, respectively, then dried with anhydrous Na.sub.2SO.sub.4, rotatory evaporated, and purified by thin-layer column chromatography (PE/EA=2:1), to obtain white solid product (4-2, 220 mg), with a yield of 93.6%.

(23) MS (ESI) m/z 180.1 [M−56+H].sup.+.

(24) (2) Previous product (4-2, 118 mg, 0.5 mmol) was dissolved in 2 mL acetonitrile, to which was added deuterated methylamine hydrochloride (105 mg, 1.5 mmol), followed by addition of DBU (304 mg, 2 mmol). The resultant mixture reacted overnight at 25° C. under stirring and then cooled to room temperature. The reaction was completed by TLC detection. The resultant mixture was washed with water and extracted with ethyl acetate. The organic layer was successively washed with 0.1 N HCl aqueous solution, saturated NaHCO.sub.3 aqueous solution and NaCl aqueous solution, respectively, and then dried with anhydrous Na.sub.2SO.sub.4, rotatory evaporated, to obtain white solid product (4, 57 mg), with a yield of 82.6%.

(25) MS (ESI) m/z 139.1 [M+H].sup.+.

(26) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.76 (m, 2H), 7.47 (dd, J=8.5, 6.1 Hz, 1H), 7.40 (t, J=7.4 Hz, 2H), 6.37 (s, 1H).

Example 5 Synthesis of Compound 5

(27) ##STR00011##

(28) (1) 5-1 (153 mg, 1 mmol) was dissolved in CH.sub.2Cl.sub.2 (5 mL), to which was added DMAP (244 mg, 2 mmol) under stirring, followed by addition of Boc anhydride (436 mg, 2 mmol). The resultant mixture was allowed to react 16 h at room temperature, till the reaction was completed by TLC detection. The reaction system was washed with 0.1 N HCl aqueous solution until DMAP was cleaned off. The organic layer was washed with saturated NaHCO.sub.3 aqueous solution and NaCl aqueous solution, respectively, then dried with anhydrous Na.sub.2SO.sub.4, rotatory evaporated, and purified by thin-layer column chromatography (PE/EA=2:1), to obtain white solid product (5-2, 200 mg), with a yield of 93.6%.

(29) MS (ESI) m/z 198.2 ([M−56+H].sup.+).

(30) (2) Previous product (5-2, 118 mg, 0.5 mmol) was dissolved in 2 mL acetonitrile, to which was added deuterated methylamine hydrochloride (105 mg, 1.5 mmol), followed by addition of DBU (304 mg, 2 mmol). The resultant mixture reacted overnight at 25° C. under stirring and then cooled to room temperature. The reaction was completed by TLC detection. The resultant mixture was washed with water and extracted with ethyl acetate. The organic layer was successively washed with 0.1 N HCl aqueous solution, saturated NaHCO.sub.3 aqueous solution and NaCl aqueous solution, respectively, and then dried with anhydrous Na.sub.2SO.sub.4, rotatory evaporated, to obtain white solid product (5, 57 mg), with a yield of 82.6%.

(31) MS (ESI) m/z 157.3 ([M+H].sup.+).

(32) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.77 (dd, J=8.7, 5.3 Hz, 2H), 7.11 (t, J=8.6 Hz, 2H), 6.12 (s, 1H).

Example 6 Synthesis of Compound 6

(33) ##STR00012##

(34) (1) N-methylcyclohexanecarboxamide (6-1, 141 mg, 1 mmol) was dissolved in CH.sub.2Cl.sub.2 (5 mL), to which was added DMAP (244 mg, 2 mmol) under stirring, followed by addition of Boc anhydride (436 mg, 2 mmol). The resultant mixture was allowed to react 16 h at room temperature, till the reaction was completed by TLC detection. The reaction system was washed with 0.1 N HCl aqueous solution until DMAP was cleaned off. The organic layer was washed with saturated NaHCO.sub.3 aqueous solution and NaCl aqueous solution, respectively, then dried with anhydrous Na.sub.2SO.sub.4, rotatory evaporated, and purified by thin-layer column chromatography (PE/EA=2:1), to obtain white solid product (6-2, 220 mg), with a yield of 83.8%.

(35) MS (ESI) m/z 186.1 ([M−56+H].sup.+).

(36) (2) Previous product (6-2, 120 mg, 0.5 mmol) was dissolved in 2 mL acetonitrile, to which was added deuterated methylamine hydrochloride (105 mg, 1.5 mmol), followed by addition of DBU (304 mg, 2 mmol). The resultant mixture reacted overnight at room temperature. The reaction was completed by TLC detection. The resultant mixture was washed with water and extracted with ethyl acetate. The organic layer was successively washed with 0.1 N HCl aqueous solution, saturated NaHCO.sub.3 aqueous solution and NaCl aqueous solution, respectively, and then dried with anhydrous Na.sub.2SO.sub.4, rotatory evaporated, to obtain white solid product (6, 62 mg), with a yield of 86.1%.

(37) MS (ESI) m/z 145.1 ([M+H].sup.+).

(38) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 5.6 (s, 1H), 2.05 (tt, J=9.2, 5.9 Hz, 1H), 1.75 (m, 4H), 1.41 (m, 2H), 1.25 (m, 4H).

Example 7 Synthesis of Compound 7

(39) ##STR00013##

(40) (1) N-methyl-3-phenylpropionamide (7-1, 163 mg, 1 mmol) was dissolved in CH.sub.2Cl.sub.2 (5 mL), to which was added DMAP (244 mg, 2 mmol) under stirring, followed by addition of Boc anhydride (436 mg, 2 mmol). The resultant mixture was allowed to react 16 h at room temperature, till the reaction was completed by TLC detection. The reaction system was washed with 0.1 N HCl aqueous solution until DMAP was cleaned off. The organic layer was washed with saturated NaHCO.sub.3 aqueous solution and NaCl aqueous solution, respectively, then dried with anhydrous Na.sub.2SO.sub.4, rotatory evaporated, and purified by thin-layer column chromatography (PE/EA=2:1), to obtain white solid product (7-2, 214 mg), with a yield of 81.4%.

(41) MS (ESI) m/z 208.1 ([M−56+H].sup.+).

(42) (2) Previous product (7-2, 131 mg, 0.5 mmol) was dissolved in 2 mL acetonitrile, to which was added deuterated methylamine hydrochloride (105 mg, 1.5 mmol), followed by addition of DBU (304 mg, 2 mmol). The resultant mixture reacted overnight at room temperature. The reaction was completed by TLC detection. The resultant mixture was washed with water and extracted with ethyl acetate. The organic layer was successively washed with 0.1 N HCl aqueous solution, saturated NaHCO.sub.3 aqueous solution and NaCl aqueous solution, respectively, and then dried with anhydrous Na.sub.2SO.sub.4, rotatory evaporated, to obtain white solid product (7, 73 mg), with a yield of 88.1%.

(43) MS (ESI) m/z 167.1 ([M+H].sup.+).

(44) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.3 (m, 2H), 7.19 (t, J=6.2 Hz, 3H), 5.57 (s, 1H), 2.96 (t, J=7.8 Hz, 2H), 2.46 (t, J=7.8 Hz, 2H).

Example 8 Synthesis of Compound 8

(45) ##STR00014##

(46) (1) N-methylhexanamide (8-1, 129 mg, 1 mmol) was dissolved in CH.sub.2Cl.sub.2 (5 mL), to which was added DMAP (244 mg, 2 mmol) under stirring, followed by addition of Boc anhydride (436 mg, 2 mmol). The resultant mixture was allowed to react 16 h at room temperature, till the reaction was completed by TLC detection. The reaction system was washed with 0.1 N HCl aqueous solution until DMAP was cleaned off. The organic layer was washed with saturated NaHCO.sub.3 aqueous solution and NaCl aqueous solution, respectively, then dried with anhydrous Na.sub.2SO.sub.4, rotatory evaporated, and purified by thin-layer column chromatography (PE/EA=2:1), to obtain white solid product (8-2, 199 mg), with a yield of 86.9%.

(47) MS (ESI) m/z 174.1 ([M−56+H].sup.+).

(48) (2) Previous product (8-2, 115 mg, 0.5 mmol) was dissolved in 2 mL acetonitrile, to which was added deuterated methylamine hydrochloride (105 mg, 1.5 mmol), followed by addition of DBU (304 mg, 2 mmol). The resultant mixture reacted overnight at room temperature. The reaction was completed by TLC detection. The resultant mixture was washed with water and extracted with ethyl acetate. The organic layer was successively washed with 0.1 N HCl aqueous solution, saturated NaHCO.sub.3 aqueous solution and NaCl aqueous solution, respectively, and then dried with anhydrous Na.sub.2SO.sub.4, rotatory evaporated, to obtain white solid product (8, 56 mg), with a yield of 84.8%.

(49) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 6.16 (s, 1H), 2.12 (t, J=7.7 Hz, 2H), 1.58 (m, 2H), 1.23 (dd, J=8.6, 4.9 Hz, 4H), 0.82 (t, J=6.8 Hz, 3H).

(50) MS (ESI) m/z 133.1 ([M+H].sup.+).

(51) In summary, the present invention provides a new method for synthesis of deuterated amides and deuterated sulfonamides, in which the reaction conditions are mild, and the route is short, including only two steps. The method can be applied to raw materials unsuitable for using prior art, improve the synthetic efficiency, and used for many amide compounds, with an incredible versatility, thereby providing a new choice for preparation of deuterated amide and sulfonamide compounds.