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), and N,N-diisopropylethylamine (0.447 mL, 3.46 mmol) was added. 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 pale 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
12. customto afford the crude title amide which
13. customwas recrystallized from diethyl ether

ORD record

ord-6208c47d1c53448eab1c8ce1d4b6f1bb

Source dataset

uspto-grants-2005_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06977254B2