Diethylamine → tert-butyl N-[(3R)-3-[3-[4-(5-ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]prop-2-ynyl]-1-methyl-2-oxo-pyrrolidin-3-yl]carbamate

Participants

Reaction Conditions

Reaction Steps

Copper iodide (26.27 mg, 0.14 mmol), followed by PdCl2(Ph3P)2 (48.41 mg, 0.07 mmol) was added portionwise to a solution of the tert-butyl N-[(3R)-1-methyl-2-oxo-3-prop-2-ynyl-pyrrolidin-3-yl]carbamate (which may be prepared as described in Description 10) (348 mg, 1.38 mmol), 4-(5-ethoxy-2-fluoro-phenyl)-2-iodo-6-methyl-pyrimidine (which may be prepared as described in D17) (642.17 mg, 1.79 mmol) and Et2NH (0.71 mL, 6.9 mmol) in THF (10 mL) under N2 and the reaction was stirred at 20° C. for 18 hrs. The solvent was evaporated and the residue was dissolved in EtOAc and washed with water. The organic layer was dried (Na2SO4) and the solvent was evaporated to afford an oil. This was purified on a Biotage SP4 using a 25 g SNAP cartridge, eluting with 50 to 100% EtOAc/i-hexane affording the tert-butyl N-[(3R)-3-[3-[4-(5-ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]prop-2-ynyl]-1-methyl-2-oxo-pyrrolidin-3-yl]carbamate (D18) (605 mg, 1.2538 mmol, 90.9% yield) as a pale yellow foam.

Provenance & Evidence