反应详情

By proceeding in a similar manner to Example 34(a) above but: (i) substituting (3-{6-[2-(2-chloro-6-fluoro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenoxy)-acetonitrile [164 mg, Example 22(f)] for (3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenoxy)-acetonitrile there is prepared 2-(3-{6-[2-(2-chloro-6-fluoro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenoxy)-N-hydroxy-acetamidine (166 mg, 94%), (ii) substituting 2-(3-{6-[2-(2-chloro-6-fluoro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenoxy)-N-hydroxy-acetamidine for 2-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl-phenoxy)-N-hydroxy-acetamidine, and (iii) subjecting the product to silica gel chromatography eluting with 0 to 7% MeOH in DCM there is prepared 3-(3-{6-[2-(2-chloro-6-fluoro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenoxymethyl)-4H-[1,2,4]oxadiazol-5-one hydrochloride [Example 34(c)] as a solid. LC/MS: RT=2.4 minutes, MS: 472 (M+H). 1H NMR (300 MHz, (CD3)2SO): □12.82 (1H, br s), 7.18-7.55 (7H, m), 6.6 (1H, s), 5.18 (2H, s), 4 (3H, s), 3.68 (2H, m), 3.08 (2H, m). IC50=0.3 nM

1. washeluting with 0 to 7% MeOH in DCM
2. customthere is prepared 3-(3-{6-[2-(2-chloro-6-fluoro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenoxymethyl)-4H-[1,2,4]oxadiazol-5-one hydrochloride [Example 34(c)] as a solid