tert-butyl N-(1-cyanocyclopropyl)carbamate → tert-butyl N-[1-(5-bromopyrimidin-2-yl)cyclopropyl]carbamate

Participants

Reaction Conditions

Reaction Steps

[1-(1-Carbamimidoyl-cyclopropylcarbamoyl)-cyclopropyl]-carbamic acid tert-butyl ester hydrochloride (1.0 g, 4.2 mmol) (made from (1-cyano-cyclopropyl)-carbamic acid tert-butyl ester using a procedure similar to that of [1-(1-carbamimidoyl-cyclopropyl-carbamoyl)-cyclopropyl]-carbamic acid tert-butyl ester) and 2-bromo-3-dimethylamino-acrolein (1.1 g, 6.36 mmol) were combined in EtOH (2 mL) in a sealed tube. The reaction was capped and the mixture heated at 80° C. for 24 hours. The resulting black mixture was allowed to cool to room temperature. Methanol (20 mL) was then added to the reaction solution. The solids were filtered and the resulting solution was dried under reduced pressure. The residue was diluted with 50 mL CH2Cl2 and the solids were removed. The solution was concentrated and purified by normal phase flash chromatography on silica gel (0→50% EtOAc in hexanes) to give 800 mg of [1-(5-bromo-pyrimidin-2-yl)-cyclopropyl]-carbamic acid tert-butyl ester as an off-white solid.

Provenance & Evidence