2-(3-Oxetanylidene)acetonitrile → 2-(3-((1S,3S,4R)-3-(3H-imidazo[1, 2-a]pyrrolo[2,3-e]pyrazin-8-yl)-4-methylcyclopentylamino)oxetan-3-yl)acetonitrile

Participants

Reaction Conditions

Reaction Steps

To a solution of (1S,3R,4S)-3-methyl-4-(3-((2-(trimethylsilyl)ethoxy)methyl)-3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)cyclopentanamine (0.605 g, 1.569 mmol, prepared using FFFFF from Preparation #33, GGGGG with Preparation #E.1.1, KKKK with PFPAA, D with NaOH, KK, Y) in DMF (6 mL) was added 2-(oxetan-3-ylidene)acetonitrile (0.298 g, 3.14 mmol, J. Med. Chem. 2010, 53(8), 3227) and the reaction mixture was heated at about 80° C. for about 15 h. 2-(Oxetan-3-ylidene)acetonitrile (0.149 g, 1.569 mmol) was added and the reaction mixture was heated at about 80° C. for about 3.5 h. The reaction mixture was cooled to ambient temperature, concentrated in vacuo and the residue was purified by silica gel chromatography eluting with 0% to 10% MeOH in DCM. A second purification by silica gel chromatography eluting with 50% to 100% EtOAc in heptane followed by 10% MeOH in DCM yielded 2-(3-((1S,3S,4R)-3-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-4-methylcyclopentylamino)oxetan-3-yl)acetonitrile (0.262 g, 33%) as a sticky brown solid: LC/MS (Table 1, Method n) Rt=0.75 min; MS m/z 481 (M+H)+.

Provenance & Evidence