反应详情

To a solution of 2-(3,5-dichlorophenylamino)acetic acid (170 mg, 0.77 mmol) in DMF (5 mL) was added HOBt (156 mg, 1.16 mmol) at 0° C. and the reaction mixture was stirred for 10 min, followed by the addition of EDCI (222 mg, 1.16 mmol), (R)—N-methyl-N-(piperidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (180 mg, 0.77 mmol) and DIEA (150 mg, 1.16 mmol). The reaction mixture was allowed to warm to rt and was stirred overnight, diluted with EtOAc (50 mL) and washed with water (3×20 mL). The EtOAc layer was dried over Na2SO4 and evaporated in vacuo to give a residue that purified by column chromatography (silica gel, gradient MeOH in DCM) to afford the titled intermediate (50 mg, 14.8%). 1H NMR (400 MHz, DMSO-d6): δ 13.50 (d, J=10.8 Hz, 1H), 8.22 (s, 1H), 8.17 (m, 1H), 6.77 (s, 1H), 6.70 (s, 1H), 6.62 (s, 1H), 6.32 (m, 1H), 4.40 (d, J=12.4 Hz, 1H), 4.00 (m, 3H), 3.28 (s, 3H), 3.02 (t, J=7.8 Hz, 1H), 2.80 (m, 1H), 2.62 (t, J=7.8 Hz, 1H), 2.00 (m, 2H), 1.82 (m, 2H). LC-MS: m/z [M+1]=434.

1. stirringwas stirred overnight
2. washwashed with water (3×20 mL)
3. dry with materialThe EtOAc layer was dried over Na2SO4
4. customevaporated in vacuo
5. customto give a residue
6. customthat purified by column chromatography (silica gel, gradient MeOH in DCM)