Example 62
Step 1: tert-butyl 2-(4-(7-chloro-4-(1H-imidazol-1-yl)quinolin-2-yl)-2-oxo-1,4-diazepan-1-yl)acetate. To a solution of 4-(7-chloro-4-(1H-imidazol-1-yl)quinolin-2-yl)-1,4-diazepan-2-one (20 mg) and tert-butyl 2-bromoacetate (30 mg) in anhydrous DMF was added NaH (10 mg, 65% in mineral oil). After stirring 3 hours, the reaction mixture was diluted with EtOAc (10 mL) and carefully quenched with water (5 mL). Isolation of the organic layer and a column chromatography eluting with a gradient of hexanes and EtOAc afforded the desired intermediate tert-butyl 2-(4-(7-chloro-4-(1H-imidazol-1-yl)quinolin-2-yl)-2-oxo-1,4-diazepan-1-yl)acetate (20 mg) (MS: [M+1]+ 456).
Step 2: 2-(4-(7-chloro-4-(1H-imidazol-1-yl)quinolin-2-yl)-2-oxo-1,4-diazepan-1-yl)acetic acid. tert-butyl 2-(4-(7-chloro-4-(1H-imidazol-1-yl)quinolin-2-yl)-2-oxo-1,4-diazepan-1-yl)acetate was further treated with TFA (0.4 mL) in DCM (0.8 mL). Removal of DCM and TFA under reduced pressure and lyophilization afforded the desired product (10 mg)-2-(4-(7-chloro-4-(1H-imidazol-1-yl)quinolin-2-yl)-2-oxo-1,4-diazepan-1-yl)acetic acid (MS: [M+1]+ 400).
