Sodium hydride → 2-((1-((tert-Butyldimethylsilyl)oxy)-3-(5-(3-cyanophenyl)-1,3-dimethyl-2,4-dioxo-3,4-dihydro-1H-pyrrolo[3,4-d]pyrimidin-6(2H)-yl)propan-2-yl)oxy)-N-methoxy-N-methylacetamide

Participants

Reaction Steps

To a stirred solution of 3-(6-(3-((tert-Butyldimethylsilyl)oxy)-2-hydroxypropyl)-1,3-dimethyl-2,4-dioxo-2,3,4,6-tetrahydro-1H-pyrrolo[3,4-d]pyrimidin-5-yl)benzonitrile (Example 9a, step 1) (280 mg, 0.597 mmol) in THF (5975 μL) was added sodium hydride (60% in mineral oil) (71.7 mg, 1.792 mmol) at 0° C. The resulting red solution was warmed to room temperature and stirred for 20 minutes, before being cooled to 0° C. 2-Bromo-N-methoxy-N-methylacetamide (Example 13, step 1) (141 mg, 0.777 mmol) was then added dropwise over 5 minutes. The reaction mixture was warmed to room temperature over 3 hours and then cooled to 0° C. and quenched with saturated aqueous ammonium chloride solution (5 mL). DCM (10 mL) was added to the biphasic solution. The aqueous phase was separated and extracted with DCM (3×10 mL); the combined organic extracts were dried (MgSO4) and concentrated under reduced pressure to afford a yellow oil. The oil was purified using Teledyne ISCO (12 g, SiO2) eluting with 0-65% EtOAc/hexanes to afford the title compound as an amorphous white solid.

Provenance & Evidence