Tert-Butylamine → 6-Amino-4-(tert-butylamino)nicotinonitrile

Participants

Reaction Conditions

Reaction Steps

To a solution of 6-amino-4-fluoronicotinonitrile (intermediate 21, 1.00 g, 7.29 mmol) in DMA (18 ml) at room temperature was added tert-butylamine (2.4 ml, 22.03 mmol) and DIPEA (4.0 ml, 22.90 mmol). The reaction mixture was heated to 50° C. and stirred for one day. The temperature was increased to 70° C. and the reaction mixture was stirred for two days. The temperature was further increased to 120° C. and the reaction mixture was stirred for 8 h. The reaction mixture was then transferred into a sealed vial, additional tert-butylamine (1 mL, 9.18 mmol) was added and the mixture was continued to stir at 120° C. for another 4 days. The crude mixture was concentrated and purified by column chromatography on silica gel using a gradient of MeOH (0-3%) in DCM to yield the title compound as a white solid mixed with a brown liquid. The material was dissolved in DCM and aqueous citric acid (<10%). Layers were separated, the aqueous layer was washed with DCM.

Provenance & Evidence