Dichloromethane → HCID 15952181, compound

Participants

Reaction Steps

To a solution of 2′-acetyl-biphenyl-4-carboxylic acid of Step A (0.340 g, 1.41 mmol) in dry tetrahydrofuran (30 mL) at room temperature under nitrogen was added dry N,N-dimethylformamide (1 drop) followed by the dropwise addition of a 2.0 M solution of oxalyl chloride in dichloromethane (1.17 mL, 2.34 mmol). The reaction mixture was stirred at room temperature for 2 hours then concentrated in vacuo and the residue redissolved in dry dichloromethane (30 mL). The solution was concentrated in vacuo to afford the crude acid chloride as a cream solid. The acid chloride was dissolved in tetrahydrofuran (30 mL); N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide of Example 11 (0.300 g, 0.942 mmol) was added, followed by N,N-diisopropylethylamine (0.49 mL, 2.83 mmol) and the reaction mixture stirred at room temperature under nitrogen for 19 hours. The reaction was quenched by the addition of 2 M sodium hydroxide (20 mL), the mixture stirred vigorously for 5 minutes and then partitioned between ethyl acetate (100 mL) and 2 M sodium hydroxide (100 mL). The organic phase was separated, washed with 2 M sodium hydroxide (100 mL), water (100 mL) and brine (100 mL), dried over anhydrous magnesium sulfate, and concentrated in vacuo to give a yellow foam. Purification by flash chromatography using a solvent gradient of 1 to 3.5% methanol in dichloromethane gave a cream foam that was crystallized from ethyl acetate/hexane to afford the title compound (0.45 g, 88%) as a white solid, m.p. 149-150° C.

Provenance & Evidence