反应详情

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0 °C

To a stirred solution of 2-(7-amino-6,7-dihydro-5H-[2]pyrindin-4-yl)-5-chloro-2,3-dihydro-isoindol-1-one (126 mg, 0.42 mmol) and Et3N (1.0 mL) in DCM (10 mL) was added acetyl chloride (0.032 mL, 0.44 mmol) at 0° C. and stirred at 0° C. for 1 hour. The resulting mixture was extracted with EtOAc (2×100 mL) and the combined organic layers were washed with brine, dried over anhy. Na2SO4, filtered and concentrated in vacuo. The residue was purified by silica gel flash chromatography eluting with a 0 to 50% EtOAc-heptane gradient to give a racemic mixture of title compound (121 mg, 85%) as light yellow solid. MS: 342.1 (M+H+). This racemic mixture was then separated by chiral HPLC to afford (−)-N-[(S or R)-4-(5-chloro-1-oxo-1,3-dihydro-isoindol-2-yl)-6,7-dihydro-5H-[2]pyrindin-7-yl]-acetamide (33 mg, example 318), MS: 342.1 (M+H+) and (+)-N—[(R or S)-4-(5-chloro-1-oxo-1,3-dihydro-isoindol-2-yl)-6,7-dihydro-5H-[2]pyrindin-7-yl]-acetamide (27 mg, example 319). MS: 342.1 (M+H)+.

1. extractionThe resulting mixture was extracted with EtOAc (2×100 mL)
2. washthe combined organic layers were washed with brine
3. customdried over anhy
4. filtrationNa2SO4, filtered
5. concentrationconcentrated in vacuo
6. customThe residue was purified by silica gel flash chromatography
7. washeluting with a 0 to 50% EtOAc-heptane gradient
8. customto give