反応式
ClC1C=CC([O:6][C:7]2[C:16]3[C:11](=C[C:13](O)=[C:14](OC)[CH:15]=3)[N:10]=[CH:9]N=2)=C(F)C=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClCCl>[CH3:9][N:10]1[CH2:13][CH2:14][CH2:15][CH:16]([CH2:7][OH:6])[CH2:11]1.[CH3:9][N:10]1[CH2:13][CH2:14][CH2:15][C@@H:16]([CH2:7][OH:6])[CH2:11]1参加物
実験手順
4-(4-Chloro-2-fluorophenoxy)-7-hydroxy-6-methoxyquinazoline (12.1 g, 38 mmol), (prepared as described for the starting material in Example 5), was suspended in dichloromethane (375 ml) and treated with triphenylphosphine (29.6 g, 113 mmol) then stirred at ambient temperature for 30 minutes. (1-Methylpiperidin-3-yl)methanol (8.25 g, 63.8 mmol) and (R)-(1-methylpiperidin-3-yl)methanol (1.46 g, 11.3 mmol), (CAS 205194-11-2), giving R:S (57.5:42.5 by chiral HPLC) (9.7 g, 75 mmol) were dissolved in dichloromethane (75 ml) and added to the suspension. Diethyl azodicarboxylate (17.7 ml, 75 mmol) was added in portions using a syringe pump and the mixture was then allowed to warm to ambient temperature and stirred overnight. The residue was concentrated under vacuum then chromatographed on silica eluting with dichloromethane followed by dichloromethane/methanol/ammonia (93/6/1). The relevant fractions were combined and evaporated to give an oil. The residue was triturated with ether, filtered and dried to give (R,S)-4-(4-chloro-2-fluorophenoxy)-6-methoxy-74(1-methylpiperidin-3-yl)methoxy)quinazoline (8.7 g, 53%).
出典と根拠
- ORDレコード
- ord-927b0147c84e4c43900680fe5de1c052
- 出典データセット
- uspto-grants-2013_07
- 特許番号
- US08492560B2
関連ノート
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