1-[(3aS,4R,6aR)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-4,7-difluoro-1H-imidazo[4,5-c]pyridine → 1-[(3aS,4R,6aR)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-7-fluoro-1H-imidazo[4,5-c]pyridin-4-amine

Participants

Reaction Conditions

Reaction Steps

Liquid ammonia (200 mL) was added to a mixture of 1-[(3aS,4R,6aR)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-4,7-difluoro-1H-imidazo[4,5-c]pyridine (1-6) (2.4 g, 8.1 mmol, 1 equiv) and 3-[(3aS,4R,6aR)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-4,7-difluoro-3H-imidazo[4,5-c]pyridine (1-5) (2.5 g, 8.5 mmol, 1 equiv). The resulting solution was heated in a high pressure vessel to 85° C. for 5 days. The mixture was then concentrated and purified via flash chromatography on a 120 g silica gel column (gradient elution 0 to 100% ethyl acetate in dichloromethane and then 100% methanol to elute 1-7) to yield 1-[(3aS,4R,6aR)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-7-fluoro-1H-imidazo[4,5-c]pyridin-4-amine (1-7) as a tan solid in addition to 3-[(3aS,4R,6aR)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-7-fluoro-3H-imidazo[4,5-c]pyridin-4-amine (1-8) and recovered starting material 1-5. 1H NMR (1-7) (500 MHz, CD3 OD): δ 8.13 (s, 1H); 7.62 (d, J=3.7 Hz, 1H); 4.95-4.87 (m, 3H); 2.52-2.42 (m, 1H); 2.21-1.99 (m, 3H); 1.50 (s, 3H); 1.33 (s, 3H). LRMS m/z (M+H) 293.0 found, 293.1 required. 1H NMR (1-8) (500 MHz, CDCl3): δ 7.86-7.81 (m, 1H); 7.76-7.73 (m, 1H); 5.07 (s, 1H); 5.01 (s, 2H); 4.87 (t, J=4.6 Hz, 1H); 4.62 (d, J=6.2 Hz, 1H); 2.66-2.57 (m, 1H); 2.46-2.38 (m, 1H); 2.24-2.17 (m, 2H); 1.57 (s, 3H); 1.35-1.30 (m, 3H). LRMS m/z (M+H) 293.0 found, 293.1 required.

Provenance & Evidence