Sodium hydride → 5-(3-ethyl-4-(6-((2-(trimethyl silyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyloxy)pyrazine-2-carbonitrile

Participants

Reaction Conditions

Reaction Steps

To 3-ethyl-4-(6-((2-(trimethylsilyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanol (0.098 g, 0.24 mmol, prepared using FF from Preparation #KK.1) in DMF (1 mL) was added NaH (0.012 g, 0.29 mmol, 60% dispersion in mineral oil) portionwise. After about 5 min, 2-chloro-5-cyanopyrazine (0.039 g, 0.28 mmol, ArkPharm) was added. The reaction mixture was heated at about 70° C. for about 2 h. After cooling to ambient temperature, ice water (2 mL) was added and the mixture was extracted with DCM (3×5 mL). The organic layers were combined and the solvents were removed under reduced pressure. The residue was purified using silica gel chromatography (12 g) eluting with a gradient of 20-80% EtOAc in DCM to give 5-(3-ethyl-4-(6-((2-(trimethylsilyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyloxy)pyrazine-2-carbonitrile (0.085 g, 69%): LC/MS (Table 1, Method b) Rt=2.84 min; MS m/z: 505 (M+H)+.

Provenance & Evidence