乙基 2-氯-3-(2-氯苯基)-3-氧代丙酸乙酯

反应条件: temp:94.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of crude ethyl 2-chloro-3-(2-chlorophenyl)-3-oxopropanoate (1.390 g, 5.320 mmol) in absolute isopropyl alcohol (50.00 mL) was added N-[4-(aminocarbonothioyl)pyridin-2-yl]acetamide (1.140 g, 5.860 mmol) and the resulting solution was fitted with a condenser and stirred for 23 h at 94° C. The mixture was cooled to ambient temperature and half the solvent was removed in vacuo. Diethyl ether (30.0 mL) was added to allow the formation of the thioamide by-product. The by-product was separated by filtration and the solvent was removed in vacuo. The residue was purified by column chromatography (SiO2, elution with 0-100% EtOAc in hexanes) to provide 0.457 g of product as a yellow oil (21% 2 steps). LC/MS (AA) ES+ 402. NMR (400 MHz, d1 CDCl3) δ: 8.77 (br s, 1H), 8.37-8.35 (m, 1H), 7.71-7.70 (m, 1H), 7.50-7.46 (m, 2H), 7.41-7.46 (m, 3H), 4.24 (q, J=7.2 Hz, 2H), 2.24 (s, 3H), 1.26 (t, J=7.2 Hz, 3H). the resulting solution was fitted with a condenser The mixture was cooled to ambient temperature half the solvent was removed in vacuo Diethyl ether (30.0 mL) was added The by-product was separated by filtration the solvent was removed in vacuo The residue was purified by column chromatography (SiO2, elution with 0-100% EtOAc in hexanes)

反应条件: temp:94.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of crude ethyl 2-chloro-3-(2-chlorophenyl)-3-oxopropanoate (1.390 g, 5.320 mmol) in absolute isopropyl alcohol (50.00 mL) was added N-[4-(aminocarbonothioyl)pyridin-2-yl]acetamide (1.140 g, 5.860 mmol) and the resulting solution was fitted with a condenser and stirred for 23 h at 94° C. The mixture was cooled to ambient temperature and half the solvent was removed in vacuo. Diethyl ether (30.0 mL) was added to allow the formation of the thioamide by-product. The by-product was separated by filtration and the solvent was removed in vacuo. The residue was purified by column chromatography (SiO2, elution with 0-100% EtOAc in hexanes) to provide 0.457 g of product as a yellow oil (21% 2 steps). LC/MS (AA) ES+ 402. NMR (400 MHz, d1 CDCl3) δ: 8.77 (br s, 1H), 8.37-8.35 (m, 1H), 7.71-7.70 (m, 1H), 7.50-7.46 (m, 2H), 7.41-7.46 (m, 3H), 4.24 (q, J=7.2 Hz, 2H), 2.24 (s, 3H), 1.26 (t, J=7.2 Hz, 3H). the resulting solution was fitted with a condenser The mixture was cooled to ambient temperature half the solvent was removed in vacuo Diethyl ether (30.0 mL) was added The by-product was separated by filtration the solvent was removed in vacuo The residue was purified by column chromatography (SiO2, elution with 0-100% EtOAc in hexanes)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of 3-(2-chloro-phenyl)-3-oxo-propionicacidethylester (5.000 mL, 26.600 mmol) in ether (75.00 mL) was added dropwise sulfuryl chloride (2.800 mL, 34.600 mmol) and the resulting solution was stirred for 4 h. The reaction mixture was diluted with ether (50.0 mL) and quenched by the slow addition of a saturated aqueous solution of sodium bicarbonate (50.0 mL) and the mixture was vigorously stirred for 30 min. The organic phase was separated and dried over anhydrous MgSO4, filtered, and concentrated in vacuo to provide 6.500 g of crude product as a clear colorless oil (100%). The crude residue was used without further purification. LC/MS (AA) ES+ 261, 263. 1H NMR (400 MHz, d, CDCl3) δ: 12.47 (s, 1H), 7.49-7.32 (m, 4H), 4.39 (q, J=7.2 Hz, 2H), 1.41 (t, J=7.2 Hz, 3H). quenched by the slow addition of a saturated aqueous solution of sodium bicarbonate (50.0 mL) the mixture was vigorously stirred for 30 min The organic phase was separated dried over anhydrous MgSO4 filtered concentrated in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Using 2-methylpyrazolo[1,5-a]pyridine-3-carbothioamide hydrochloride (300 mg, 1.3 mmol) produced in Example 11(v), ethyl 2-chloro-3-(2-chlorophenyl)-3-oxopropanoate (1.0 g, 3.9 mmol) produced above and 2-propanol (20 mL) as starting materials and in the same manner as in Example 11-B(vi), the title compound (475 mg, 91%) was obtained as a yellow solid.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Using ethyl 3-(2-chlorophenyl)-3-oxopropanoate (1.0 g, 5.0 mmol), sulfuryl chloride (810 mg, 6.0 mmol) and diethyl ether (50 mL) as starting materials and in the same manner as in Example 20(i), the title compound (1.0 g, 85%) was obtained as a colorless oil.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Using 2-methylpyrazolo[1,5-a]pyridine-3-carbothioamide hydrochloride (300 mg, 1.3 mmol) produced in Example 11(v), ethyl 2-chloro-3-(2-chlorophenyl)-3-oxopropanoate (1.0 g, 3.9 mmol) produced in the above and 2-propanol (20 mL) as starting materials and in the same manner as in Example 11-B(vi), the title compound (475 mg, 91%) was obtained as a yellow solid.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Using ethyl 3-(2-chlorophenyl)-3-oxopropanoate (1.0 g, 5.0 mmol), sulfuryl chloride (810 mg, 6.0 mmol) and diethyl ether (50 mL) as starting materials and in the same manner as in Example 20(i), the title compound (1.0 g, 85%) was obtained as a colorless oil.