Sodium borohydride → HCID 90067516, compound

Participants

Reaction Conditions

Reaction Steps

Sodium borohydride (1.3 mg, 0.034 mmol) was added to a stirred solution of (3R,3aR,6R,6aS)-3-[[6-chloro-5-(4-phenylphenyl)-1H-imidazo[4,5-b]pyridin-2-yl]oxy]-6-hydroxy-3,3a,5,6a-tetrahydro-2H-furo[3,2-b]furan-6-carbaldehyde (5.4 mg, 0.011 mmol) in methanol (0.5 ml) that had been cooled to 0° C. in an ice bath. After 1.5 hours, additional sodium borohydride (3.0 mg, 0.079 mmol) was added to the reaction mixture. After an additional 1.5 hours, additional sodium borohydride (2.8 mg, 0.074 mmol) was added to the reaction mixture. After another hour, the reaction mixture was placed in the refrigerator overnight. In the morning, the reaction mixture was removed from the refrigerator and placed in an ice bath. Additional sodium borohydride (3.2 mg, 0.085 mmol) was added to the reaction mixture. After 1.5 hours, the reaction mixture was removed from the ice bath and allowed to warm to room temperature. The reaction mixture was directly purified by preparative HPLC reverse phase (C-18), using a 30×150 mm Sunfire™ column and eluting with a 20%-80% acetonitrile/water+0.05% TFA gradient followed by a 80% 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 C25H22ClN3O5 479.12 observed m/e: 480.18 (M+H)+ (Rt 1.16/2 min); 1H NMR δ (ppm) (CD3OD): 7.86 (s, 1H), 7.73-7.77 (m, 4H), 7.71 (d, J=7.8 Hz, 2H), 7.48 (t, J=7.6 Hz, 2H), 7.38 (t, J=6.8 Hz, 1H), 5.56 (qt, J=5.4 Hz, 1H), 4.98 (t, J=5.3 Hz, 1H), 4.30 (d, J=5.0 Hz, 1H), 4.20 (dd, J=5.6 Hz, J=10.3 Hz, 1H), 4.15 (dd, J=5.1 Hz, J=10.0 Hz, 1H), 3.80 (d, J=8.7 Hz, 1H), 3.67 (d, J=8.8 Hz, 1H), 3.52-3.58 (m, 2H).

Provenance & Evidence