Aniline → HCID 11212557, compound

Participants

Reaction Steps

A solution of [(2,4-dichloropyrimidin-5-yl)methyl](4-methoxyphenyl)amine (200 mg, 0.70 mmol) (from Example 1d supra) in anhydrous tetrahydrofuran (24 mL) was treated with n-butyllithium (1.6 M solution in hexanes, 0.53 mL, 0.84 mmol) (Aldrich) at −78° C. This was followed by addition of cyclohexyl isocyanate (90 μL, 88 mg, 0.70 mmol) (Aldrich). The resulting mixture was stirred and slowly warmed up to room temperature within a period of 2 hours. The reaction mixture was then partitioned between ethyl acetate and brine. The organic layer was collected, dried over sodium sulfate, filtered and concentrated to a residue that was purified by chromatography with a silica gel column using a 0–60% ethyl acetate in hexanes gradient. The intermediate that was obtained from this purification was dissolved in aniline (2 mL) (Aldrich), a catalytic amount of 4-(dimethylamino)pyridine (Aldrich) was added and the mixture was then heated at 100° C. After stirring overnight the mixture was cooled, and purified by silica gel column chromatography with a 0–60% ethyl acetate in hexanes gradient. The solid obtained from this purification was dissolved in tetrahydrofuran and then precipitated with excess of pentane to give 1-cyclohexyl-3-(4-methoxy-phenyl)-7-phenylamino-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one as a beige solid. (Yield 78 mg, 26%).

Provenance & Evidence