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

Participants

Reaction Conditions

Reaction Steps

Liquid ammonia (150 mL) was added to a mixture of 4,7-difluoro-1-((3aS,4S,6aR)-5-fluoro-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-1H-imidazo[4,5-c]pyridine (5-7) (140 mg, 0.45 mmol, 1 equiv) and 4,7-difluoro-3-((3aS,4S,6aR)-5-fluoro-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-3H-imidazo[4,5-c]pyridine (5-8) (160 mg, 0.51 mmol, 1 equiv). The resulting solution was heated in a high pressure vessel to 100° C. for 3 days. The mixture was then concentrated and purified via flash chromatography (40 g SiO2; 20-100% EtOAc in hexanes, holding at 100% EtOAc to elute 5-9) to yield 7-fluoro-1-((3aS,4S,6aR)-5-fluoro-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-1H-imidazo[4,5-c]pyridin-4-amine (5-9) as a white solid and 7-fluoro-3-((3aS,4R,6aR)-5-fluoro-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-3H-imidazo[4,5-c]pyridin-4-amine (5-10) as a white solid. 1H NMR (5-9) (500 MHz, CDCl3): δ 7.77 (d, J=3.5 Hz, 1H); 7.71 (s, 1H); 5.74 (s, 1H); 5.58 (s, 1H); 5.36 (m, 1H); 5.12 (s, 2H); 4.75 (t, J=5 Hz, 1H); 1.55 (s, 3H); 1.36 (s, 3H). LRMS m/z (M+H) 308.9 found, 309.1 required. LRMS m/z (5-10) (M+H) 308.9 found, 309.1 required.

Provenance & Evidence