Ethylenediamine → (3R,3aR,6R,6aR)-6-[[6-chloro-5-[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl]-1H-imidazo[4,5-b]pyridin-2-yl]oxy]-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol

Participants

Reaction Conditions

Reaction Steps

A vial was charged with 4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydro-furo[3,2-b]furan-6-yl]oxy]-6-chloro-1H-imidazo[4,5-b]pyridin-5-yl]benzonitrile (24.8 mg, 0.062 mmol), ethylenediamine (0.5 ml, 7.46 mmol), and carbon disulfide (5 μl, 0.083 mmol). The reaction mixture was heated to 50° C. for 19 h. The reaction mixture was cooled to room temperature before being concentrated under reduced pressure to 0.1 mL. The concentrated reaction mixture was purified by preparative HPLC reverse phase (C-18), using a 30×150 mm Sunfire™ column and eluting with a 0%-30% acetonitrile/water+0.05% TFA gradient, followed by a 30% acetonitrile/water+0.05% TFA flush. The product fractions were combined, evaporated under reduced pressure, and lyophilized from ethanol and benzene to give the title compound as a white solid. LC-MS: calculated for C21H20ClN5O4 441.12 observed m/e: 442.19 (M+H)+ (Rt 0.25/2 min); 1H NMR δ (ppm) (CD3OD): 7.95 (s, 4H), 7.85 (s, 1H), 5.54 (qt, J=5.3 Hz, 1H), 4.96 (t, J=5.2 Hz, 1H), 4.46 (t, J=5.0 Hz, 1H), 4.26-4.30 (m, 1H), 4.16 (dd, J=5.7 Hz, J=10.3 Hz, 1H), 4.14 (s, 4H), 4.11 (dd, J=4.7 Hz, J=10.2 Hz, 1H), 3.89 (dd, J=6.8 Hz, J=8.1 Hz, 1H), 3.59 (t, J=8.6 Hz, 1H).

Provenance & Evidence