1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (2Z)-3-(5-chloro-6-{[(3R)-1-cyclopentyl-3-pyrrolidinyl]amino}-3-pyridinyl)-2-fluoro-N-(tetrahydro-2H-pyran-2-yloxy)acrylamide

Participants

Reaction Steps

A mixture of (2Z)-3-(5-chloro-6-{[(3R)-1-cyclopentyl-3-pyrrolidinyl]amino}-3-pyridinyl)-2-fluoroacrylic acid (658 mg), O-(tetrahydro-2H-pyran-2-yl)hydroxylamine (229 mg), HOBt (264 mg) and EDCI (303 mg) in DMF (15 ml) was stirred at ambient temperature for 15 hours. The reaction mixture was poured into a mixture of AcOEt-H2O and the organic layer was washed with brine and dried over MgSO4. The solvent was evaporated in vacuo and the residue was chromatographed on silicagel eluting with AcOEt-MeOH (95:5). The eluted fractions containing the desired product were collected and evaporated in vacuo to give (2Z)-3-(5-chloro-6-{[(3R)-1-cyclopentyl-3-pyrrolidinyl]amino}-3-pyridinyl)-2-fluoro-N-(tetrahydro-2H-pyran-2-yloxy)acrylamide (620 mg).

Provenance & Evidence