[N:1]1[CH:6]=[CH:5][CH:4]=[N:3][C:2]=1[C:7]1[CH:15]=[CH:14][C:10]([C:11](O)=[O:12])=[CH:9][CH:8]=1.C(Cl)(=O)C([Cl:19])=O.ClCCl>O1CCCC1.CN(C)C=O>[N:1]1[CH:6]=[CH:5][CH:4]=[N:3][C:2]=1[C:7]1[CH:15]=[CH:14][C:10]([C:11]([Cl:19])=[O:12])=[CH:9][CH:8]=1To a solution of 4-pyrimidin-2-ylbenzoic acid of Step A (0.283 g, 1.41 mmol) in dry tetrahydrofuran (20 mL) at room temperature under nitrogen was added N,N-dimethylformamide (1 drop, cat) followed by a 2.0 M solution of oxalyl chloride in dichloromethane (1.41 mmol, 2.82 mmol) and the reaction mixture was stirred at room temperature for 3 hours. The mixture was then concentrated in vacuo to afford 4-pyrimidin-2-yl-benzoyl chloride as a yellow syrup. The crude acid chloride was dissolved in dry tetrahydrof-uran (5 mL), added to a suspension of N-(pyridin-3-ylmethyl)-10,11-dihydro-5Hpyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide of Example 76, Step C (0.300 g, 0.942 mmol), and N,N-diisopropylethylamine (0.49 mL, 2.83 mmol) in dry tetrahydrofuran (5 mL), and the reaction mixture stirred at room temperature under nitrogen for 20 hours. The reaction was then quenched by the addition of 2 M sodium hydroxide (10 mL) and the mixture partitioned between ethyl acetate (50 mL) and 2 M sodium hydroxide (50 mL). The organic phase was separated, washed with 2 M sodium hydroxide (2×50 mL), water (50 mL) and brine (50 mL), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to afford a yellow foam. Purification by flash chromatography using a solvent gradient of 1 to 5% methanol in dichloromethane gave an cream foam that was crystallized from diethyl ether/hexane to afford the title compound (0.395 g, 84%) as white solid, m.p. 234-236° C.
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