Ethanol → HCID 69316787, compound

Participants

Reaction Steps

A suspension of 4-{[6-(4-fluoro-phenyl)-4-[1,2,4]triazol-4-yl-pyrido[3,2-d]pyrimidin-2-ylamino]-methyl}-benzenesulfonamide (638 mg, 1.34 mmol) in 10 ml THF was added to a solution of 21% (w/w) NaOEt in EtOH (1.50 ml, 4.03 mmol) in 20 ml of dry THF over 5 min. The triazole flask was rinsed once with 5 ml THF and the rinse was added to the reaction flask. The reaction was stirred at room temperature for 15 min. Analysis by reversed phase HPLC/MS indicated the reaction was complete. The pH was adjusted to 7 with 10% acetic acid/EtOAc and then concentrated in vacuo. The residue was partitioned between EtOAc and H2O. The aqueous layer was extracted twice with EtOAc. The combined organics were washed twice with water and once with brine, dried over MgSO4, filtered and concentrated. The solid was absorbed onto SiO2, and purified by eluting onto a 30 g SiO2 column with CH2Cl2/MeOH. The fractions containing the desired compound as determined by LC/MS were combined and concentrated. The solid thus obtained was dissolved in DMF and re-purified by reverse phase HPLC using acetonitrile/H2O in 4 runs. The pure fractions from each run were combined and the acetonitrile was removed in vacuo. The resulting aqueous suspension was neutralized with excess saturated aqueous NaHCO3, and extracted three times with EtOAc. The organics were dried over MgSO4, filtered and concentrated. The material was solidified by addition of MeOH. The solid was dried at high vacuum for 24 hrs, giving 110 mg of 4-{[4-ethoxy-6-(4-fluoro-phenyl)-pyrido[3,2-d]pyrimidin-2-ylamino]-methyl}-benzenesulfonamide (Example 109) as a white powder. MS (m/z) 454 [M+H]+.

Provenance & Evidence