Oxalyl chloride → HCID 11715978, compound

To a suspension of 4-{[(tert-butoxycarbonyl)amino]methyl}benzoic acid of Step A (3.55 g, 0.0141 mmol) in dry dichloromethane (40 mL) at room temperature under nitrogen was added dry N,N-dimethylformamide (2 drops, cat.) followed by a 2.0 M solution of oxalyl chloride in dichloromethane (14.1 mL, 0.0283 mol) and the reaction mixture stirred at room temperature for 4.5 hours. The reaction mixture was then concentrated in vacuo to afford (4-chlorocarbonyl-benzyl)carbamic acid tert-butyl ester as a white solid. The crude acid chloride was dissolved in dry tetrahydrofuran (20 mL), added to a suspension of N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide of Example 76, Step C (3 g, 9.42 mmol), and N,N-diisopropylethylamine (4.92 mL, 28.27 mmol) in dry tetrahydrofuran (20 mL), and the reaction mixture stirred at room temperature for 19 hours. The reaction was quenched by the addition of 2 M sodium hydroxide (20 mL) and then partitioned between ethyl acetate (200 mL) and 2 M sodium hydroxide (200 mL). The separated organic phase was washed with 2 M sodium hydroxide (200 mL), water (200 mL) and brine (200 mL), dried over magnesium sulfate, and concentrated in vacuo to afford an orange solid (3.95 g). Purification by flash chromatography using a solvent gradient of 1 to 5% methanol in dichloromethane gave a colorless glass that was recrystallized from ethyl acetate/hexane to afford the title compound (1.29 g, 25%) as a cream crystalline solid, m.p. 171° C.

1. concentrationThe reaction mixture was then concentrated in vacuo

ORD record

ord-fc751aca849944a489a4d5ecb8479328

Source dataset

uspto-grants-2010_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07678787B2