反应详情

The title compound was synthesized following the approach outlined in Procedure 2J (Example 145), substituting 4-(4-isopropylpiperazin-1-yl)-2-nitroaniline (procedure shown below) in step (b) and omitting steps (d) and (e) to afford the free base of the title compound (0.1 g, overall yield: 9.7%) as an off-white solid. MS (ESI): 643.1 [M+H]+. 85% H3PO4 was slowly added to a solution of N-(2-((6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylureido)pyrimidin-4-yl)amino)-5-(4-isopropylpiperazin-1-yl)phenyl)acrylamide (0.1 g) in 95% THF-MeOH (5 mL). The resulting reaction mixture was then allowed to stir at room temperature for 30 min., evaporated the solvent and triturated with diethyl ether, dried under vacuum to afford the title compound (0.16 g) as a off white solid. 1HNMR (DMSO-d6, 400 MHz): δ 12.08 (s, 1H), 9.62 (s, 1H), 8.76 (s, 1H), 8.32 (s, 1H), 7.30 (d, 2H), 6.89 (d, 1H), 6.81 (d, 1H), 6.46-6.49 (m, 1H), 6.21-6.25 (m, 2H), 5.72 (d, 1H), 3.93 (s, 6H), 3.35-3.41 (m, 1H), 3.23 (s, 3H), 3.12-3.17 (m, 4H), 2.67-2.70 (m, 41H), 1.05-1.11 (m, 6H); MS (ESI): 643.3 (M+1); HPLC: 95.41%, rt: 6.48 min.

1. customThe resulting reaction mixture
2. customevaporated the solvent
3. customtriturated with diethyl ether
4. customdried under vacuum