Lithium Hexamethyldisilazide → HCID 118036625, compound

Participants

Reaction Conditions

Reaction Steps

A solution of phenyl 7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate (intermediate 3, 50 mg, 0.152 mmol) in THF (1.5 ml) was treated with 2-amino-5-cyanopyrimidine (45.7 mg, 0.381 mmol), cooled to 0° C. and treated with LHMDS (1M in THF, 0.305 ml, 0.305 mmol). The reaction mixture was stirred at 0° C. for 1 h, allowed to warm to room temperature and stirred for 45 min. More 2-amino-5-cyanopyrimidine (22.9 mg, 0.190 mmol) and LHMDS (1M in THF, 0.152 ml, 0.152 mmol) were added, the reaction mixture was stirred for 35 min, quenched by addition of sat. aq. NH4Cl and extracted with EtOAc (2×). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by normal phase chromatography (12 g silica gel cartridge, heptanes/EtOAc 100:0 to 0:100). The product containing fractions were concentrated and re-purified by reverse phase chromatography (13 g C18 cartridge, 0.1% TFA in water/acetonitrile 95:5 to 5:95). The product containing fractions were treated with sat. aq. NaHCO3, concentrated until the organic solvent had been removed and extracted with DCM (3×). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure to give the title compound as a white solid. (UPLC-MS 1) tR 0.87 min; ESI-MS 355.2 [M+H]+.

Provenance & Evidence