[Cl:1][C:2]1[C:10]([F:11])=[CH:9][CH:8]=[C:7]([F:12])[C:3]=1[C:4](Cl)=[O:5].[NH2:13][CH2:14][C:15]1([CH:26]2[CH2:31][CH2:30][CH2:29][CH2:28][N:27]2[CH3:32])[CH2:18][N:17]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:16]1.C(N(CC)CC)C>ClCCl>[Cl:1][C:2]1[C:10]([F:11])=[CH:9][CH:8]=[C:7]([F:12])[C:3]=1[C:4]([NH:13][CH2:14][C:15]1([CH:26]2[CH2:31][CH2:30][CH2:29][CH2:28][N:27]2[CH3:32])[CH2:16][N:17]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:18]1)=[O:5]2-chloro-3,6-difluorobenzoyl chloride (0.38 ml, 2.7 mmol) was added to tert-butyl 3-(aminomethyl)-3-(1-methylpiperidin-2-yl)azetidine-1-carboxylate (0.55 g, 1.9 mmol) in dichloromethane (6 ml) and triethylamine (0.54 ml, 3.9 mmol) at 0° C. The reaction was stirred at 0° C. for 15 mins, before warming to room temperature. After 30 mins, lc-ms showed complete consumption of starting material. The reaction was quenched and the resulting mixture was partitioned between dichloromethane and water. The organic phase was washed with brine, dried over anhydrous magnesium sulfate and evaporated to dryness. Purification by flash column chromatography on silica gel eluting with dichloromethane (containing 1% ammonia) on a gradient of methanol (0-8%) led to tert-butyl 3-{[(2-chloro-3,6-difluorobenzoyl)amino]methyl}-3-(1-methylpiperidin-2-yl)azetidine-1-carboxylate as a white solid. m/z (M++H) 458.
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