2-(2-oxaspiro[3.3]heptan-6-ylidene)acetonitrile

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 7-(1-methyl-1H-pyrazol-4-yl)-5-(1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine (25 mg; 0.094 mmol), 2-(2-oxaspiro[3.3]heptan-6-ylidene)acetonitrile (19 mg; 0.14 mmol) and DBU (7.2 mg; 0.047 mmol) in acetonitrile (1 mL) was stirred in a sealed vial at 50° C. for 24 hours. The solvent was removed under reduced pressure and the material was purified by silica gel chromatography, eluting with (6% ammonium hydroxide in methanol)/methylene chloride (1:25 to 1:15 gradient) to provide pure desired product as a white solid (27.5 mg). MS (apci) m/z=401.1 (M+H). The solvent was removed under reduced pressure the material was purified by silica gel chromatography eluting with (6% ammonium hydroxide in methanol)/methylene chloride (1:25 to 1:15 gradient)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of diethyl cyanomethylphosphonate (82 mg; 0.464 mmol) in THF (2 mL) at 0° C. under nitrogen was added potassium t-butoxide (0.51 mmol; 1M solution in THF) and the mixture was stirred at 0° C. for 1 hour. A solution of 2-oxaspiro[3.3]heptan-6-one (52 mg; 0.464 mmol) in THF (1 mL) was added. A precipitate formed and further THF (1 mL) was added to enhance the stirring. The reaction mixture was allowed to stir for 4 hours at ambient temperature. The reaction mixture was partitioned between saturated aqueous ammonium chloride (10 mL) and ethyl acetate (10 mL). The phases were separated and the aqueous phase was extracted with ethyl acetate (3×10 mL). The extracts were combined, dried (sodium sulfate), filtered and evaporated under reduced pressure. The material was purified by silica gel chromatography eluting with hexane/ethyl acetate (3:2) to give the product as a colorless oil (20 mg). A precipitate formed to stir for 4 hours at ambient temperature The reaction mixture was partitioned between saturated aqueous ammonium chloride (10 mL) and ethyl acetate (10 mL) The phases were separated the aqueous phase was extracted with ethyl acetate (3×10 mL) dried (sodium sulfate) filtered evaporated under reduced pressure The material was purified by silica gel chromatography eluting with hexane/ethyl acetate (3:2)