p-Toluenesulfonic acid → (R)-2-(1-amino-2-methylpropyl)-3-benzyl-7-chloroquinazolin-4(3H)-one
反応式
C(OC(=O)[NH:7][C@@H:8]([C:12]1[N:21]([CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:20](=[O:29])[C:19]2[C:14](=[CH:15][C:16]([Cl:30])=[CH:17][CH:18]=2)[N:13]=1)[CH:9]([CH3:11])[CH3:10])(C)(C)C.CC1C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[NH2:7][C@@H:8]([C:12]1[N:21]([CH2:22][C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:20](=[O:29])[C:19]2[C:14](=[CH:15][C:16]([Cl:30])=[CH:17][CH:18]=2)[N:13]=1)[CH:9]([CH3:11])[CH3:10]参加物
4
実験手順
A dry 3-necked, round bottomed flask, equipped with a magnetic stirrer, nitrogen inlet, heating mantle and water condenser, is charged with 60 mL of toluene, 4.42 g (10 mmol) of (R)-[1-(3-benzyl-7-chloro-4-oxo-3,4-dihydro-quinazolin-2-yl)-2-methylpropyl]-carbamic acid tert-butyl ester (the compound of Formula 107 or 203 prepared, e.g., as described in Example 6.4 or 6.3), and 4.20 g of PTSA. The mixture is heated to reflux for 1 h, during which the evolution of gas is observed. Upon cessation of gas evolution, TLC analysis (hexanes/ethyl acetate 7:3) indicates complete reaction. The mixture is cooled to room temperature, initially forms an oil that separates at the bottom of the flask and quickly solidifies into a brown solid. Toluene is decanted and 50 mL of saturated potassium bicarbonate (room temperature) is added to the solid with stirring followed by the addition of 25 mL of water. The resulting white solid is collected by filtration to afford the title compound of Formula 301, (R)-2-(1-amino-2-methyl-propyl)-3-benzyl-7-chloro-3H-quinazolin-4-one.