[O:1]=[S:2]1(=[O:12])[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.[Cl:31][C:32]1[CH:51]=[CH:50][C:35]([O:36][C:37]2[C:46]3[C:41](=[CH:42][C:43](O)=[C:44]([O:47][CH3:48])[CH:45]=3)[N:40]=[CH:39][N:38]=2)=[C:34]([F:52])[CH:33]=1.C(P(CCCC)CCCC)CCC>C(OCC)C.C(Cl)Cl>[Cl:31][C:32]1[CH:51]=[CH:50][C:35]([O:36][C:37]2[C:46]3[C:41](=[CH:42][C:43]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][S:2](=[O:1])(=[O:12])[CH2:3][CH2:4]4)=[C:44]([O:47][CH3:48])[CH:45]=3)[N:40]=[CH:39][N:38]=2)=[C:34]([F:52])[CH:33]=13-(1,1-dioxotetrahydro-4H-1,4-thiazin-4-yl)propan-1-ol (4.2 g) and 1,1′-(azodicarbonyl)dipiperidine (11.7 g) were added in turn to a mixture of 4(4-chloro-2-fluorophenoxy)-7-hydroxy-6-methoxyquinazoline (5.0 g), tributylphosphine (11.1 ml) and methylene chloride (150 ml). The resultant mixture was stirred at ambient temperature overnight. The mixture was diluted with diethyl ether (300 ml) and the precipitate was removed by filtration. The filtrate was evaporated and the residue was purified by column chromatography on silica using a 19:1 mixture of methylene chloride and methanol as eluent. The material so obtained was triturated under ethyl acetate and dried to give 4-(4-chloro-2fluorophenoxy)-7-[3-(1,1-dioxotetrahydro-4H-1,4-thiazin-4-yl)propoxy]-6-methoxyquinazoline (5.4 g); NMR Spectrum: (DMSOd6) 1.86 (m, 2H), 2.65 (t, 2H), 2.92 (m, 4H), 3.08 (m, 4H), 3.97 (s, 3H), 4.26 (t, 2H), 7.4 (m, 1H), 7.42 (s, 1H), 7.56 (m, 2H), 7.68 (m, 1H), 8.54 (s, 1H).
読み込み中…