(1R,4R)-4-(4,7-difluoro-3H-imidazo[4,5-c]pyridin-3-yl)cyclopent-2-enyl acetate → (1R,4R)-4-(4-amino-7-fluoro-3H-imidazo[4,5-c]pyridin-3-yl)cyclopent-2-enol

Participants

Reaction Conditions

Reaction Steps

Liquid ammonia (150 mL) was added to a mixture of (1R,4R)-4-(4,7-difluoro-1H-imidazo[4,5-c]pyridin-1-yl)cyclopent-2-enyl acetate (4-1) (312 mg, 1.1 mmol, 1 equiv) and (1R,4R)-4-(4,7-difluoro-3H-imidazo[4,5-c]pyridin-3-yl)cyclopent-2-enyl acetate (4-2) (408 mg, 1.5 mmol, 1 equiv). The resulting solution was heated in a high pressure vessel to 100° C. for 2 days. The mixture was then concentrated and purified via reverse phase chromatography (5-95% CH3CN/water with 0.1% TFA modifier) to yield (1R,4R)-4-(4-amino-7-fluoro-1H-imidazo[4,5-c]pyridin-1-yl)cyclopent-2-enol (4-3) as a white solid and (1R,4R)-4-(4-amino-7-fluoro-3H-imidazo[4,5-c]pyridin-3-yl)cyclopent-2-enol (4-4) as a white solid. 1H NMR (4-3) (500 MHz, CD3 OD): δ 8.03 (s, 1H); 7.61 (d, J=3.5 Hz, 1H); 6.31 (m, 1H); 6.20 (m, 1H); 5.93 (m, 1H); 5.09 (m, 1H); 2.40-2.50 (m, 1H); 2.27-2.37 (m, 1H). LRMS m/z (M+H) 235.0 found, 235.1 required. 1H NMR (4-4) (500 MHz, CD3 OD): δ 8.12 (s, 1H); 7.64 (d, J=2.5 Hz, 1H); 6.37 (m, 1H); 6.27 (m, 1H); 6.11 (m, 1H); 4.92 (m, 1H); 2.40-2.50 (m, 1H); 2.27-2.37 (m, 1H). LRMS m/z (M+H) 235.0 found, 235.1 required.

Provenance & Evidence