1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 76604970, compound

Participants

Reaction Steps

To a solution of 2-(1-carbonyl-2-vinyl-cyclopropylcarbamoyl)-4-(6-methoxy-isoquinolin-1-yloxy)-pyrrolidine-1-carboxylic acid tert-butyl ester (1.00 g, 2.01 mmol) in DMF (10 mL) was added HATU (1.14 g, 3.02 mmol, 1.5 equiv.) and DIPEA (0.52 mL, 2.98 mmol, 1.5 equiv.). The solution was stirred at room temperature for 15 min before sulfamic acid 1-propyl-cyclopropyl ester (0.71 mg, 4.00 mmol, 2 equiv.) and DBU (1.2 mL, 8.02 mmol, 4 equiv.) were added. The reaction was then stirred for an additional 15 h. The solution was diluted with EtOAc and washed twice with 1M aqueous HCl and Brine. The organic layer was dried over MgSO4 and concentrated in vacuo. The desired sulfamate was precipitated from EtOH/H2O to provide 4-(6-methoxy-isoquinolin-1-yloxy)-2-[1-(1-propyl-cyclopropoxysulfonylaminocarbonyl)-2-vinyl-cyclopropylcarbamoyl]-pyrrolidine-1-carboxylic acid tert-butyl ester (520 mg, 39%). The mother liquor was concentrated in vacuo and further purified by column chromatography (50→100% EtOAc/hexanes) to provide additional sulfamate. Precipitation from EtOH/H2O provided 4-(6-methoxy-isoquinolin-1-yloxy)-2-[1-(1-propyl-cyclopropoxysulfonylaminocarbonyl)-2-vinyl-cyclopropylcarbamoyl]-pyrrolidine-1-carboxylic acid tert-butyl ester (244 mg, 18%): LCMS found 659.0 [M+H]+.

Provenance & Evidence