[NH2:1][C:2]1[C:3]([F:16])=[CH:4][C:5]([OH:15])=[C:6]([N:8]2[C:12](=[O:13])[N:11]([CH3:14])[N:10]=[N:9]2)[CH:7]=1.Cl[C:18]1[N:23]=[C:22]([NH:24][C@@H:25]2[CH2:33][C@H:32]3[N:28]([CH2:29][CH2:30][CH2:31]3)[C:27]([CH3:35])([CH3:34])[CH2:26]2)[C:21]([C:36]#[N:37])=[CH:20][N:19]=1.[C:38]1([S:44]([OH:47])(=[O:46])=[O:45])[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>CC(O)C>[CH3:34][C:27]1([CH3:35])[CH2:26][C@H:25]([NH:24][C:22]2[C:21]([C:36]#[N:37])=[CH:20][N:19]=[C:18]([NH:1][C:2]3[C:3]([F:16])=[CH:4][C:5]([OH:15])=[C:6]([N:8]4[C:12](=[O:13])[N:11]([CH3:14])[N:10]=[N:9]4)[CH:7]=3)[N:23]=2)[CH2:33][C@H:32]2[N:28]1[CH2:29][CH2:30][CH2:31]2.[C:38]1([S:44]([OH:47])(=[O:46])=[O:45])[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1A mixture of 1-(5-amino-4-fluoro-2-hydroxyphenyl)-4-methyl-1H-tetrazol-5(4H)-one (210 mg), (7R,8aS)-N-(2-chloro-5-cyanopyrimidin-4-yl)-octahydro-5,5-dimethylindolizin-7-amine (220 mg), and benzenesulfonic acid (200 mg) in IPA (2 mL) were heated to 80° C. for overnight. After cooling to ambient temperature, the crude mixture was concentrated to dryness. The crude product was absorbed onto silica gel and purified by CombiFlash chromatography (2N NH3 in MeOH/CH2Cl2=0-30%) to give compound 1-(5-(4-((7R,8aS)-octahydro-5,5-dimethylindolizin-7-ylamino)-5-cyanopyrimidin-2-ylamino)-4-fluoro-2-hydroxyphenyl)-4-methyl-1H-tetrazol-5(4H)-one (540 mg with some benzenesulfonic acid).
読み込み中…