反应详情

To a solution of 5-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)nicotinic acid 19 (0.028 mmol) in DMF (1 mL) is added HATU (0.033 mmol) and DIEA (0.084 mmol) at rt. The resulting mixture is stirred for 2 min then N-boc-piperazine (0.03 mmol) is added. The reaction mixture is stirred at it for 12 h and directly purified by preparative LCMS to give tert-butyl 4-(5-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)nicotinoyl)piperazine-1-carboxylate. The residue is treated with TFA (1 mL) at rt for 1 h, concentrated under vacuum, and directly purified by preparative LCMS to afford (5-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)pyridin-3-yl)(piperazin-1-yl)methanone B3. NMR (400 MHz, d3-CH3CN) δ 9.32 (bs, 1H), 8.86 (s, 2H), 8.67 (bs, 1H), 8.41 (bs, 1H), 7.75 (d, J=12.0 Hz, 2H), 7.33 (d, J=12.0 Hz, 2H), 6.87 (t, J=73 Hz, 1H), 4.20 (bs, 4H), 3.30 (bs, 4H). MS (m/z) (M+1)+: 427.1.

1. stirringThe reaction mixture is stirred at it for 12 h
2. customdirectly purified by preparative LCMS