Dichloromethane → N-(2-((5aR,6R)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl)ethyl)-1,3,4-thiadiazol-2-amine

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Reaction Steps

To a stirred mixture of 2-((5aR,6R)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl)-1-methoxyethanol (18 mg, 0.05 mmol), 1,3,4-thiadiazol-2-amine (10 mg, 0.1 mmol), and anhydrous methylene chloride (0.5 mL) was added chlorotriisopropoxytitanium solution (1 M in hexanes, 0.2 mL, 0.2 mmol) at RT under nitrogen. The mixture was stirred at RT for 15 min before sodium triacetoxyborohydride (106 mg, 0.5 mmol) was added. The mixture was stirred at RT for 1 hr and quenched by the addition of saturated aqueous sodium bicarbonate solution (3 mL). The aqueous layer was separated and extracted with ethyl acetate (3×2 mL). The combined organic solutions were dried (Na2SO4) and concentrated. Prep TLC (silica gel, 50% acetone in ethyl acetate) gave N-(2-((5aR,6R)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl)ethyl)-1,3,4-thiadiazol-2-amine (6 mg, 0.015 mmol, 30% yield) as a solid.

Provenance & Evidence