反应详情

To a cooled solution of 2-(3,5-dichlorophenylamino)acetic acid (102 mg, 0.45 mmol) at 0° C. in anhydrous DMF (5 mL), HOBt (135 mg, 0.68 mmol) was added and the reaction mixture was stirred for 10 min before EDCI (132 mg 0.68 mmol), (S)—N-(piperidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (100 mg, 0.45 mmol) and DIEA (117 mg, 0.90 mmol) were added in succession. The reaction mixture was allowed to warm to rt and stirred overnight. After completion of the reaction as indicated by TLC, the reaction mixture was diluted with EtOAc (50 mL) and was washed with water (3×20 mL). The EtOAc layer was then dried over Na2SO4 and evaporated in vacuo to give a residue that was purified by column chromatography (silica gel, gradient MeOH in CH2Cl2) to afford the titled intermediate (62 mg, 32%). 1H NMR (400 MHz, CDCl3): δ 11.42 (bs, 1H), 8.58 and 8.49 (2s, 1H), 7.98 (s, 1H), 6.71 and 6.68 (2s, 2H), 6.41 and 6.39 (2s, 2H), 5.29-5.18 (m, 1H), 4.40-4.09 (m, 2H), 3.94-3.42 (m, 3H), 3.18-3.03 (m, 1H), 2.27-2.20 (m, 1H), 1.97-1.56 (m, 4H). LC-MS: m/z [M+1]=420.

1. additionwere added in succession
2. customAfter completion of the reaction
3. washwas washed with water (3×20 mL)
4. dry with materialThe EtOAc layer was then dried over Na2SO4
5. customevaporated in vacuo
6. customto give a residue that
7. customwas purified by column chromatography (silica gel, gradient MeOH in CH2Cl2)