Acetic Acid → HCID 178484130, compound

Participants

Reaction Conditions

Reaction Steps

To a cooled (0° C.) and stirred solution of cis/trans-3-(1-aminocyclobutan-3-yl)-5-[(1,2,4-triazol-1-yl)methyl]- 1H-indole (270 mg, 1.0 mmol) in anhydrous methanol (20 ml) were added sodium cyanoborohydride (127 mg, 2.0 mmol), glacial acetic acid (289 μl, 5.0 mmol) and a solution of formaldehyde (38% w/v aqueous solution; 200 μl) in absolute methanol (3 ml). The reaction mixture was then allowed to warm to room temperature and it was stirred for 1.5 hours before saturated aqueous potassium carbonate (10 ml) was added and the methanol was removed under vacuum. The aqueous residue was extracted with ethyl acetate (3×50 ml) and the combined organic solutions were washed with brine (2×15 ml), dried (Na2SO4) and concentrated. The remaining residue was purified by preparative TLC (silica gel, dichloromethane-methanol-ammonia, 90:10:1) to give 102 mg (34%) of 3-[cis-1-(dimethylamino)cyclobutan-3-yl]-5-[(1,2,4-triazol-1-yl)methyl]-1H-indole (less polar isomer) and 132 mg (44%) of 3-[trans-1-(dimethyl amino)cyclobutan-3-yl]-5-[(1,2,4-triazol-1-yl) methyl]-1H-indole (more polar isomer). The hydrogen oxalate salts were prepared and showed:

Provenance & Evidence