Sodium hydride → 1-Cyclopentyl-3-(3-ethoxy-2,6-difluoro-phenyl)-7-methylsulfanyl-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one

Participants

Reaction Steps

A solution of 1.00 g (2.53 mmol) of cyclopentyl-{5-[(3-ethoxy-2,6-difluoro-phenylamino)-methyl]-2-methylsulfanyl-pyrimidin-4-yl }-amine in 20 mL of dry THF was cooled to 0C. To this solution was added 0.25 g (6.33 mmol, 2.5 equivalents) of NaH as a 60% oil suspension. The reaction was stirred for 0.5 hour, the ice bath was removed, and the reaction was stirred for another 0.5 hour. To the reaction was added 1.24 g (7.60 mmol, 3.0 equivalents) of CDI. After 0.5 hour the reaction was warmed to reflux for 24 hours. The reaction was concentrated in vacuo and the residue was partitioned between dichloromethane and a saturated solution of ammonium chloride. The dichloromethane layer was washed again with ammonium chloride and then once with a saturated solution of NaCl, dried, and concentrated in vacuo. The crude material was eluted onto a Biotage 90 g silica gel column that had been pre-equilibrated with 3:1 hexane/ethyl acetate using the same solvent mixture. Fractions of pure product were combined and concentrated in vacuo to give 0.86 g (81%) of the title compound as a foam: mp 45° C. dec. MS (APCI) (m+1)/z 421.2 Analysis calculated for C20H22F2N4SO2: C, 57.13; H, 5.27; N, 13.32. Found: C, 57.12; H, 5.08; N, 13.21.

Provenance & Evidence