ethyl 4-(4-chlorophenyl)sulfanyl-3-oxobutanoate

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Chlorothiophenol (1.1 g, 7.61 mmol) was mixed with ethyl 4-chloro-acetoacetate (0.95 mL, 7.00 mmol) in CH2Cl2 (100 mL) at 0° C. Triethyl amine (1.5 mL, 10.8 mmol) was then added drop wise. After the resulting suspension was stirred at 0° C. for another 30 min, the reaction mixture was poured into water, and the aqueous layer was extracted with EtOAc. The combined organic layer was washed by saturated NaHCO3, HCl (0.25 N), brine, concentrated in vacuo, and purified by flash column chromatography (ethyl acetate/hexanes=1/9) to afford TC-I-164 (1.82 g, 96%) as light yellow oil. Exposure to hydrazine in refluxing ethanol, generated TC-II-165. the aqueous layer was extracted with EtOAc The combined organic layer was washed by saturated NaHCO3, HCl (0.25 N), brine concentrated in vacuo purified by flash column chromatography (ethyl acetate/hexanes=1/9) to afford TC-I-164 (1.82 g, 96%) as light yellow oil

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Chlorothiophenol (1.1 g, 7.61 mmol) was mixed with ethyl 4-chloro-acetoacetate (0.95 mL, 7.00 mmol) in CH2Cl2 (100 mL) at 0° C. Triethyl amine (1.5 mL, 10.8 mmol) was then added drop wise. After the resulting suspension was stirred at 0° C. for another 30 min, the reaction mixture was poured into water, and the aqueous layer was extracted with EtOAc. The combined organic layer was washed by saturated NaHCO3, HCl (0.25 N), brine, concentrated in vacuo, and purified by flash column chromatography (ethyl acetate/hexanes=1/9) to afford TC-I-164 (1.82 g, 96%) as light yellow oil. Exposure to hydrazine in refluxing ethanol, generated TC-II-165. the aqueous layer was extracted with EtOAc The combined organic layer was washed by saturated NaHCO3, HCl (0.25 N), brine concentrated in vacuo purified by flash column chromatography (ethyl acetate/hexanes=1/9) to afford TC-I-164 (1.82 g, 96%) as light yellow oil

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Chlorothiophenol (1.1 g, 7.61 mmol) was mixed with ethyl 4-chloro-acetoacetate (0.95 mL, 7.00 mmol) in CH2Cl2 (100 mL) at 0° C. Triethyl amine (1.5 mL, 10.8 mmol) was then added drop wise. After the resulting suspension was stirred at 0° C. for another 30 min, the reaction mixture was poured into water, and the aqueous layer was extracted with EtOAc. The combined organic layer was washed by saturated NaHCO3, HCl (0.25 N), brine, concentrated in vacuo, and purified by flash column chromatography (ethyl acetate/hexanes=1/9) to afford TC-I-164 (1.82 g, 96%) as light yellow oil. Exposure to hydrazine in refluxing ethanol, generated TC-II-165. the aqueous layer was extracted with EtOAc The combined organic layer was washed by saturated NaHCO3, HCl (0.25 N), brine concentrated in vacuo purified by flash column chromatography (ethyl acetate/hexanes=1/9) to afford TC-I-164 (1.82 g, 96%) as light yellow oil

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of formamidine acetate (1508 mg, 14.48 mmol), ethyl 4-(4-chlorophenylthio)-3-oxobutanoate Part A (790 mg, 2.90 mmol) and phenol (8178 mg, 87 mmol) was stirred at 140° C. for 18 hours. After the reaction cooled to RT, the mixture was diluted with saturated NaHCO3 (65 mL) and extracted with EtOAc (80 mL). The EtOAc layer was dried over Na2SO4 and concentrated. The crude product was purified by flash chromatography (silica gel/hexane-EtOAc 100:0 to 0:100 gradient, using LC-MS to identify fractions containing the desired product) to afford 6-((4-chlorophenylthio)-methyl)pyrimidin-4(3H)-one 10B (169 mg, 22% yield). 1H NMR (400 MHz, CD3OD) δ ppm 7.97 (1H, s), 7.07-7.25 (4H, m), 6.06 (1H, s), 3.80 (2H, s). After the reaction cooled to RT extracted with EtOAc (80 mL) The EtOAc layer was dried over Na2SO4 concentrated The crude product was purified by flash chromatography (silica gel/hexane-EtOAc 100:0 to 0:100 gradient containing the desired product)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 4-chlorobenzenethiol (1.75 g, 12.15 mmol) and K2CO3 (3.36 g, 24.30 mmol) in DMF (40 mL) was added ethyl 4-chloro-3-oxobutanoate (2.0 g, 12.15 mmol). The mixture was stirred at RT for 18 hours, diluted with saturated NaHCO3 (40 mL) and extracted with EtOAc (50 mL). The EtOAc layer was dried over Na2SO4 and concentrated. The crude product was purified by flash chromatography (silica gel/hexane-EtOAc 100:0 to 0:100 gradient, using LC-MS to identify fractions containing the desired product) to afford ethyl 4-(4-chlorophenylthio)-3-oxobutanoate 10A (2.07 g, 59% yield). 1H NMR (500 MHz, Chloroform-D) δ ppm 7.22-7.32 (4H, m), 4.18 (2H, q, J=7.15 Hz), 3.79 (2H, s), 3.62 (2H, s), 1.27 (3H, t, J=7.01 Hz). extracted with EtOAc (50 mL) The EtOAc layer was dried over Na2SO4 concentrated The crude product was purified by flash chromatography (silica gel/hexane-EtOAc 100:0 to 0:100 gradient containing the desired product)