反应详情

温度

40 °C

To 4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorobenzenesulfonic acid (1.2 g, 2.1 mmol, 1.1 eq) in DCM (6 mL) was added thionyl chloride (3 mL) followed by catalytic DMF (30 drops). After heating at 40° C. for 1 h, the reaction mixture was concentrated under reduced pressure and the resulting sulfonyl chloride was further dried on a high-vacuum pump for several hours. A solution of this sulfonyl chloride in MeCN (12 mL) was added to another flask containing (S)-4-amino-5-methoxy-N,N,N-trimethyl-5-oxopentan-1-aminium chloride hydrochloride (2.0 g, 7.5 mmol, 4.0 eq) and aq. Na2CO3 (2.0 g, 18.7 mmol, 10 eq, in 12 mL of water). The reaction mixture was stirred vigorously for 10 min. The organic layer was removed by pipette and concentrated to yield (S)-4-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenylsulfonamido)-5-methoxy-N,N,N-trimethyl-5-oxopentan-1-aminium chloride (1.56 g, over theoretical), which was used in the next step without purification. MS (EI) m/z 601 (M+).

1. concentrationthe reaction mixture was concentrated under reduced pressure
2. dry with materialthe resulting sulfonyl chloride was further dried on a high-vacuum pump for several hours
3. additionA solution of this sulfonyl chloride in MeCN (12 mL) was added to another flask
4. customThe organic layer was removed by pipette
5. concentrationconcentrated