tert-butyl N-(1-amino-2-methyl-1-sulfanylidenepropan-2-yl)carbamate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-Bromosuccinimide (0.763 g, 4.29 mmol) was added to a solution of 2-propen-1-yl {3-[(2-chloro-4-pyrimidinyl)acetyl]-2-fluorophenyl}carbamate (1.5 g, 4.29 mmol) in dichloromethane (DCM) (50 mL). After 1 h of stirring, 1,1-dimethylethyl (2-amino-1,1-dimethyl-2-thioxoethyl)carbamate (0.936 g, 4.29 mmol) was added to the reaction mixture and heated to 80° C. for 2 h. The reaction mixture was diluted with 150 cc of EtOAc and washed with water (5×100 cc). The EtOAc layer was dried over MgSO4 and filtered and concentrated in vacuo. The residue was purified via chromatography on silica gel using Hex to 25% EtOAc in Hex to obtain the title compound (1.28 g, 54% yield). MS (ESI): 548.3 [M+H]+ washed with water (5×100 cc) The EtOAc layer was dried over MgSO4 filtered concentrated in vacuo The residue was purified via chromatography on silica gel using Hex to 25% EtOAc in Hex

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N2-{[(1,1-dimethylethyl)oxy]carbonyl}-2-methylalaninamide (3.87 g, 19.13 mmol), Lawesson's reagent (7.74 g, 19.13 mmol) and tetrahydrofuran (THF) (100 mL) was heated to 50° C. for 3 hours. The reaction was concentrated, added 150 cc of EtOAc and washed with sat'd NaHCO3 (3×100 cc), water and brine. The EtOAc layer was concentrated and the residue was purified via chromatography on silica gel eluted Hex to 1:1 Hex/EtOAc to obtain the title compound (2.04 g, 48% yield). The reaction was concentrated added 150 cc of EtOAc washed with sat'd NaHCO3 (3×100 cc), water and brine The EtOAc layer was concentrated the residue was purified via chromatography on silica gel eluted Hex to 1:1 Hex/EtOAc

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of tert-butyl 1-amino-2-methyl-1-thioxopropan-2-ylcarbamate (Example 12 b, 0.218 g, 1 mmol) and 1,1-dimethoxy-N,N-dimethylethanamine (CAN 18871-66-4, 0.16 g, 1.2 mmol) in methylene chloride (10 mL) was stirred at room temperature for 24 h. Then it was concentrated to give crude product, which was used directly in the next step without further purification (0.28 g, 98%) as yellow oil; MS (EI): m/e 288.2 [M+H]+. Then it was concentrated to give crude product, which was used directly in the next step without further purification (0.28 g, 98%) as yellow oil

反応条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of tert-butyl 1-amino-2-methyl-1-thioxopropan-2-ylcarbamate (5.31 g, 24 mmol), 2-bromo-1,1-dimethoxyethane (CAN:7252-83-7, 5.11 g, 30 mmol) and TsOH (0.49 g, 3 mmol) in acetic acid (50 mL) was stirred at 120° C. for 4 h. After evaporation of solvents, the residue was diluted with ethyl acetate (50 mL) and water (50 mL). The water phase was washed with ethyl acetate (3×50 mL). Then water phase was lyophilized to give the title compound as brown solid (2.1 g, 65%); MS (LC/MS): 143.1 [M+H]+. After evaporation of solvents the residue was diluted with ethyl acetate (50 mL) and water (50 mL) The water phase was washed with ethyl acetate (3×50 mL)

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of tert-butyl 1-amino-2-methyl-1-oxopropan-2-ylcarbamate (10 g, 49 mmol) in toluene (200 mL) was added Lawesson's reagent (CAN 19172-47-5, 10 g, 25 mmol). The suspension was heated to 90° C. and stirred for 6 h. After evaporation of solvents, the residue was purified by column chromatography (silica gel, 120 g) eluting with 30% ethyl acetate in petroleum ether to yield the title compound (6 g, 56%); MS: m/e 241.2 [M+Na]+. After evaporation of solvents the residue was purified by column chromatography (silica gel, 120 g) eluting with 30% ethyl acetate in petroleum ether

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of tert-butyl 1-amino-2-methyl-1-oxopropan-2-ylcarbamate (10 g, 49 mmol) in toluene (200 mL) was added Lawesson's reagent (CAN 19172-47-5, 10 g, 25 mmol). The suspension was heated to 90° C. and stirred for 6 h. After evaporation of solvents, the residue was purified by column chromatography (silica gel, 120 g) eluting with 30% ethyl acetate in petroleum ether to yield the title compound (6 g, 56%); MS: m/e 241.2 [M+Na]+. After evaporation of solvents the residue was purified by column chromatography (silica gel, 120 g) eluting with 30% ethyl acetate in petroleum ether

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of tert-butyl 1-amino-2-methyl-1-thioxopropan-2-ylcarbamate (Example 12 b, 0.218 g, 1 mmol) and 1,1-dimethoxy-N,N-dimethylethanamine (CAN 18871-66-4, 0.16 g, 1.2 mmol) in methylene chloride (10 mL) was stirred at room temperature for 24 h. Then it was concentrated to give crude product, which was used directly in the next step without further purification (0.28 g, 98%) as yellow oil; MS (EI): m/e 288.2 [M+H]+. Then it was concentrated to give crude product, which was used directly in the next step without further purification (0.28 g, 98%) as yellow oil

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of tert-butyl 1-amino-2-methyl-1-thioxopropan-2-ylcarbamate (Example 12 b, 0.218 g, 1 mmol) and 1,1-dimethoxy-N,N-dimethylethanamine (CAN 18871-66-4, 0.16 g, 1.2 mmol) in methylene chloride (10 mL) was stirred at room temperature for 24 h. Then it was concentrated to give crude product, which was used directly in the next step without further purification (0.28 g, 98%) as yellow oil; MS (EI): m/e 288.2 [M+H]+. Then it was concentrated to give crude product, which was used directly in the next step without further purification (0.28 g, 98%) as yellow oil

反応条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of tert-butyl 1-amino-2-methyl-1-thioxopropan-2-ylcarbamate (5.31 g, 24 mmol), 2-bromo-1,1-dimethoxyethane (CAN:7252-83-7, 5.11 g, 30 mmol) and TsOH (0.49 g, 3 mmol) in acetic acid (50 mL) was stirred at 120° C. for 4 h. After evaporation of solvents, the residue was diluted with ethyl acetate (50 mL) and water (50 mL). The water phase was washed with ethyl acetate (3×50 mL). Then water phase was lyophilized to give the title compound as brown solid (2.1 g, 65%); MS (LC/MS): 143.1 [M+H]+. After evaporation of solvents the residue was diluted with ethyl acetate (50 mL) and water (50 mL) The water phase was washed with ethyl acetate (3×50 mL)

反応条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of tert-butyl 1-amino-2-methyl-1-thioxopropan-2-ylcarbamate (5.31 g, 24 mmol), 2-bromo-1,1-dimethoxyethane (CAN:7252-83-7, 5.11 g, 30 mmol) and TsOH (0.49 g, 3 mmol) in acetic acid (50 mL) was stirred at 120° C. for 4 h. After evaporation of solvents, the residue was diluted with ethyl acetate (50 mL) and water (50 mL). The water phase was washed with ethyl acetate (3×50 mL). Then water phase was lyophilized to give the title compound as brown solid (2.1 g, 65%); MS (LC/MS): 143.1 [M+H]+. After evaporation of solvents the residue was diluted with ethyl acetate (50 mL) and water (50 mL) The water phase was washed with ethyl acetate (3×50 mL)

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of tert-butyl 1-amino-2-methyl-1-oxopropan-2-ylcarbamate (10 g, 49 mmol) in toluene (200 mL) was added Lawesson's reagent (CAN 19172-47-5, 10 g, 25 mmol). The suspension was heated to 90° C. and stirred for 6 h. After evaporation of solvents, the residue was purified by column chromatography (silica gel, 120 g) eluting with 30% ethyl acetate in petroleum ether to yield the title compound (6 g, 56%); MS: m/e 241.2 [M+Na]+. After evaporation of solvents the residue was purified by column chromatography (silica gel, 120 g) eluting with 30% ethyl acetate in petroleum ether