Bromide ion → 7-(2,2-Dimethyl-propyl)-6-(3-methyl-2,4-dioxo-1-propyl-1,3,8-triaza-spiro[4,5]dec-8-ylmethyl)-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile

Participants

Reaction Steps

To a solution of 3-methyl-2,4-dioxo-1,3,8-triaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester (1 g, 3.53 mmol) in DMF (10 ml), Na (211 mg, 5.4 mmol) and n-propryl bromide (384 □1, 4.24 mmol) are added at 0° C. The reaction mixture is stirred at ambient temperature for 4 h, quenched with saturated ammonium chloride and extracted with AcOEt. The organic layer is washed with brine, dried over magnesium sulfate and filtrated. To a solution of 3-methyl-2,4-dioxo-1-propyl-1,3,8-triaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester (3.53 mmol) in CH2Cl2 (5 ml), TFA (5 ml) are added at 0° C. The reaction mixture is stirred at room temperature for 1 h. After removal of the solvent, H2O is added to the residue and lyophilized. To the crude product (1.5 g, 4.42 mmol) in DMSO (10 ml), potassium carbonate (1.2 g, 8.82 mmol) and 6-bromomethyl-7-(2,2-dimethyl-propyl)-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile (0.7 g, 2.28 mmol) are added to the mixture at ambient temperature. The reaction mixture is stirred at ambient temperature for 3 h, quenched with saturated ammonium chloride and extracted with AcOEt. The combined extracts are washed with H2O, brine and dried over magnesium sulfate. The combined extracts are concentrated and the residue is purified by column chromatography on silica gel using n-hexane:AcOEt=3:1 to give 386 mg of desired product in 24% yield.

Provenance & Evidence