Dimethylformamide → HCID 22219705, compound

To a mixture of 5-chloro-4-iodo-2-methoxy benzoic acid of Step C (0.900 g, 2.88 mmol) and N,N-dimethylformamide (6.7 mL, 86.4 mmol) in anhydrous dichloromethane (14.4 mL) was added dropwise oxalyl chloride (0.263 mL, 3.02 mmol). The mixture was heated to reflux for 1 hour, then cooled to room temperature and evaporated to dryness. Fresh anhydrous dichloromethane (25 mL) was added, the resulting solution was concentrated and the residue dried in vacuo. The crude acid chloride thus obtained and 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (0.584 g, 3.17 mmol) were combined in anhydrous dichloromethane (14.4 mL), followed by addition of N,N-diisopropylethyl amine (0.447 mL, 3.46 mmol). After stirring at room temperature for 18 hours, the reaction mixture was diluted with dichloromethane (15 mL) and washed sequentially 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 title amide which was recrystallized from diethyl ether to provide 1.23 g of slightly orange crystals, m.p. 191-192° C.

1. temperatureThe mixture was heated
2. temperatureto reflux for 1 hour
3. customevaporated to dryness
4. additionFresh anhydrous dichloromethane (25 mL) was added
5. concentrationthe resulting solution was concentrated
6. customthe residue dried in vacuo
7. customThe crude acid chloride thus obtained
8. washwashed sequentially 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

ORD record

ord-6881e385ab264b0b96660a117c07d310

Source dataset

uspto-grants-2008_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07326700B2