반응 #156714

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2-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(4-fluoro-2-methylphenyl)-3-pyridinyl]-N,2-dimethylpropanamide

intermediate 4D

2-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(4-fluoro-2-methylphenyl)-3-pyridinyl]-N,2-dimethylpropanamide

methyl (2S)-2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-4-pentynoate

Intermediate 1

methyl (2S)-2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-4-pentynoate

triphenylphosphine

diisopropylamine

→

title compound

수율 55.2%

methyl (2S)-5-[5-[{2-[3,5-bis(trifluoromethyl)phenyl]-2-methylpropanoyl}(methyl)amino]-4-(4-fluoro-2-methylphenyl)-2-pyridinyl]-2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-4-pentynoate

수율 55.2%

용매

triethylamine

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후처리

1. 1
   기타The solvents were evaporated
2. 2
   기타the residue was purified by flash chromatography (Biotagesystem) on silica gel using a column 40+M and cyclohexane to cyclohexane/ethyl acetate 7:3 as eluent

실험 절차

A solution of 2-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(4-fluoro-2-methylphenyl)-3-pyridinyl]-N,2-dimethylpropanamide (WO2005/002577 intermediate 4D, 1 g, 1.877 mmol), methyl (2S)-2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-4-pentynoate (Intermediate 1, 1.279 g, 5.63 mmol), Pd(PPh3)2Cl2 (0.066 g, 0.094 mmol), copper(I) iodide (0.018 g, 0.094 mmol), triphenylphosphine (0.049 g, 0.188 mmol) in triethylamine (2 ml)/diisopropylamine (8 ml) was heated at 100° C. under microwave irradiation for 30 mins. The solvents were evaporated and the residue was purified by flash chromatography (Biotagesystem) on silica gel using a column 40+M and cyclohexane to cyclohexane/ethyl acetate 7:3 as eluent to afford the title compound (750 mg, 1.036 mmol, 55.2% yield) as a white solid. UPLC: Rt 1.02 min, m/z 724 [M+H]+.

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