Cesium carbonate → HCID 178419395, compound

Participants

Reaction Conditions

Reaction Steps

Tert-butyl(trans-3-(benzo[d]thiazol-2-ylamino)cyclobutyl)carbamate (intermediate 10, 1.16 g, 3.63 mmol) was dissolved in a mixture of dichloromethane (50 mL) and trifluoroacetic acid (10 mL). The solution was stirred for 20 minutes then evaporated to dryness under reduced pressure and further dried under high vacuum at 60° C. The crude amine was treated with cesium carbonate (2.85 g, 8.75 mmol) and dissolved in dry dimethylsulfoxide (5 mL). 3-Bromo-2-fluoropyridine (0.400 ml, 3.89 mmol) was added in one portion and the reaction heated at 110° C. After 2½ hours, another portion of 3-bromo-2-fluoropyridine (0.100 mL) was added and the reaction heated for another 12 hours. Additional 3-bromo-2-fluoropyridine (0.100 mL) was added and the heating continued for another 2 hours. The reaction was cooled and partitioned between 20% saturated sodium bicarbonate (200 mL) and ethyl acetate (200 mL). The organic phase was dried with magnesium sulfate and evaporated to dryness under reduced pressure. Purification using silica chromatography (hexane to ethyl acetate gradient) gave the desired trans-N1-(benzo[d]thiazol-2-yl)-N3-(3-bromopyridin-2-yl)cyclobutane-1,3-diamine (0.869 g, 2.316 mmol, 63.8% yield) as a yellow oil that solidified on standing.

Provenance & Evidence