Diisopropylethylamine → HCID 178519939, compound

Participants

Reaction Conditions

Reaction Steps

Diisopropylethylamine (0.32 mL, 1.8 mmol) was added dropwise to a mixture of 6,7-difluoro-3-hydroxyquinoxaline-2-carboxylic acid (100 mg, 0.44 mmol), racemic 2-(3-chlorobenzyl)pyrrolidine (72 mg, 0.37 mmol) and O-HATU (210 mg, 0.55 mmol) in anhydrous DMF (2.0 mL) at room temperature under nitrogen, after which the mixture was heated to 85° C. and stirred for 4 h. The cooled mixture was directly purified by flash column chromatography on silica gel, eluting with 10% concentrated ammonium hydroxide in methanol/methylene chloride (gradient from 2:98 to 10:90), to provide a yellow solid. The residue was further purified by preparative reverse phase HPLC to provide (+/−)-[2-(3-chlorobenzyl)pyrrolidin-1-yl](6,7-difluoro-3-hydroxyquinoxalin-2-yl)methanone as a light yellow solid: 1H NMR (400 MHz, CDCl3, ˜2:1 mixture of rotamers) δ 7.72-7.63 (m, 2H, rotamers A and B), 7.38-7.21 (m, 2H, rotamers A and B), 7.10-7.03 (m, 1H, rotamers A and B), 6.90-6.79 (m, 1H, rotamers A and B), 4.63-4.56 (m, 1H, rotamers A and B), 3.89-3.82 (m, 1H, rotamer B), 3.76-3.69 (m, 1H, rotamer A), 3.56-3.47 (m, 1H, rotamers A and B), 3.33 (dd, 1H, rotamer A), 3.17 (q, 1H, rotamer B), 2.94-2.89 (m, 1H, rotamer A), 2.86-2.63 (m, 1H, rotamer B), 2.12-1.92 (m, 2H, rotamers A and B), 1.91-1.73 (m, 2H, rotamers A and B) ppm; ESI MS m/z 404 [M+H]+.

Provenance & Evidence