Oxalyl chloride → HCID 21947764, compound

To a stirred mixture of 4-bromo-3-methyl benzoic acid (21.5 g, 100 mmol) and N,N-dimethylformamide (0.251 mL, 3.00 mmol) in anhydrous dichloromethane (200 mL) was added dropwise oxalyl chloride (9.16 mL, 105 mmol). The mixture was heated to reflux for 1.5 hours, then cooled to room temperature and the solvent evaporated. Fresh anhydrous dichloromethane (200 mL) was added and the resulting solution concentrated and the residue was dried in vacuo. The crude acid chloride thus obtained and 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (17.5 g, 95.0 mmol) were combined in anhydrous dichloromethane (200 mL), followed by addition of N,N-diisopropylethyl amine (19.2 mL, 110 mmol). After stirring at room temperature for 18 hours, the reaction mixture was washed with 1 N hydrochloric acid, 1 N sodium hydroxide and brine. The organic phase was dried over anhydrous magnesium sulfate, filtered and concentrated to afford the crude amide which was recrystallized from ethyl acetate to provide slightly orange crystals (34.8 g) of the title compound, m.p. 175–176° C.

1. temperatureThe mixture was heated
2. temperatureto reflux for 1.5 hours
3. customthe solvent evaporated
4. additionFresh anhydrous dichloromethane (200 mL) was added
5. concentrationthe resulting solution concentrated
6. customthe residue was dried in vacuo
7. customThe crude acid chloride thus obtained
8. washthe reaction mixture was washed with 1 N hydrochloric acid, 1 N sodium hydroxide and brine
9. dry with materialThe organic phase was dried over anhydrous magnesium sulfate
10. filtrationfiltered
11. concentrationconcentrated
12. customto afford the crude amide which
13. customwas recrystallized from ethyl acetate

ORD record

ord-7e8943c13e64430fa199037d9168c72d

Source dataset

uspto-grants-2006_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07022699B2