tert-Butyl ((3R,4R)-4-aminotetrahydro-2H-pyran-3-yl)carbamate → tert-butyl (3R,4R)-4-(6-carbamoyl-5-(4-methyl-6-propylpyridin-2-ylamino)pyridazin-3-ylamino)tetrahydro-2H-pyran-3-ylcarbamate

Participants

Reaction Conditions

Reaction Steps

To a solution of 6-chloro-4-(4-methyl-6-propylpyridin-2-ylamino)pyridazine-3-carboxamide (73 mg, 239 μmol, prepared as described in example 38) in NMP (796 μL) was added tert-butyl (3R,4R)-4-aminotetrahydro-2H-pyran-3-ylcarbamate (206.4 mg, 956 μmol) in 4 portions approximately every 12 h over 48 h and heated at 140° C. in the periods between additions. After 48 h, the mixture was diluted with ethyl acetate and brine. The phases were separated then the organic phase was washed with brine (3×), concentrated in vacuo, and purified by chromatography (silica, 1 to 5% methanol in dichloromethane) to give tert-butyl (3R,4R)-4-(6-carbamoyl-5-(4-methyl-6-propylpyridin-2-ylamino)pyridazin-3-ylamino)tetrahydro-2H-pyran-3-ylcarbamate (27 mg, 56 μmol, 23%) as a light brown solid. MS (EI/CI) m/z: 486.2 [M+H].

Provenance & Evidence