反应详情

To a suspension of methanesulfonylacetic acid (40 mg, 0.29 mmol) in DCM (2.0 mL) under nitrogen was added 1-chloro-N,N,2-trimethylpropenylamine (48 μL, 0.37 mmol), and the mixture was stirred at RT for 2 hr. The resulting mixture was added to a solution of (Intermediate Q) (37 mg, 0.07 mmol) and DIPEA (51 μL, 0.29 mmol) in DCM (2.0 mL) and stirring continued at RT for 3 hr. The reaction mixture was stirred with 1% NH3 in MeOH (3.0 mL) for 45 min and then evaporated in vacuo. The residue was subjected to SCX capture and release and was then purified by flash column chromatography (SiO2, 12 g, 0-70% [5% MeOH in EtOAc] in isohexane, gradient elution) to afford the title compound (Example 51) as a white powder (13 mg, 28%): m/z 627 (M+H)+ (ES+). 1H NMR (400 MHz, DMSO-d6) δ: 1.29 (9H, s), 2.39 (3H, s), 3.10 (3H, s), 4.36 (2H, s), 6.40 (1H, s), 6.71 (1H, dd), 7.33-7.38 (3H, overlapping m), 7.47 (2H, m), 7.56 (1H, m), 7.65 (1H, m), 7.69 (1H, m), 7.85 (1H, d), 7.96 (1H, d), 8.11 (1H, d), 8.22 (1H, d), 8.91 (1H, br s), 9.23 (1H, br s), 10.96 (1H, br s).

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4. customwas then purified by flash column chromatography (SiO2, 12 g, 0-70% [5% MeOH in EtOAc] in isohexane, gradient elution)