1-Pyrrolidineethanamine → HCID 53372694, compound

Participants

Reaction Steps

A mixture of 4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-fluorobenzoic acid (Compound 224, 100 mg, 0.21 mmol), 2-(pyrrolidin-1-yl)ethanamine (32 mg, 0.28 mmol), HATU (106 mg, 0.28 mmol), and DIEA (0.1 mL, 0.63 mmol) in DCM (3 mL) and DMF (1.5 mL) was stirred at room temperature for 18 h. Brine and EtOAc were added and the aqueous layer was extracted with EtOAc (4×), the organics were combined, dried over sodium sulfate, and evaporated to dryness. The residue was purified by column chromatography on silica gel eluting with 0 to 10% MeOH/DCM to afford impure desired product that was repurified by reverse phase HPLC (acetonitrile/water:TFA). The fractions containing the desired compound were combined, acetonitrile was removed in vacuo, and the remaining aqueous layer was treated with a saturated solution of sodium bicarbonate. The aqueous layer was extracted with DCM (3×), the organics were combined, dried over sodium sulfate, and evaporated to dryness to afford 88 mg of 4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-fluoro-N-(2-(pyrrolidin-1-yl)ethyl)benzamide as an off-white solid. LCMS [M+1]+ 561.1.

Provenance & Evidence