Morpholine → HCID 66600187, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 5-bromo-N-(6-methoxypyridin-3-yl)-3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-amine (0.310 g, 0.625 mmol) (Example 64 intermediate), morpholine (0.054 g, 0.625 mmol) (Aldrich, St. Louis, Mo.), sodium tert-butoxide (0.090 g, 0.937 mmol) (Aldrich, St. Louis, Mo.), tris(dibenzylideneacetone)dipalladium (0) (0.011 g, 0.012 mmol) (Aldrich, St. Louis, Mo.) and 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.022 g, 0.037 mmol) (Strem Chemicals, Inc., Newburyport, Mass.) in dioxane (100 mL, 941 mmol) was deoxygenated and stirred at 95-100° C. under N2 for three hours. The reaction mixture was diluted with ethyl acetate and washed with water (3×). The organic layer was concentrated, adsorbed onto a plug of silica gel and chromatographed through a RediSep®, Teledyne ISCO, Lincoln, Nebr., pre-packed silica gel column (120 g), eluting with a gradient of 10% to 50% ethyl acetate in hexane to give N-(6-methoxypyridin-3-yl)-3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)-5-morpholinopyridin-2amine (0.105 g, 33% yield). The residue was treated with trifluoroacetic acid (Aldrich, St. Louis, Mo.) and dichloromethane to give N-(3-(2-methyl-9H-purin-6-yl)-5-morpholinopyridin-2-yl)-1H-indazol-4-amine. MS (ESI pos. ion) m/z 419 (M+H)+. 1H NMR (400 MHz, d6-DMSO) δ 12.46 ((br. s., 1H); 9.56 ((br. s., 1H); 8.56 (d, J=0.39 Hz, 1H); 8.51-8.53 (m, 1H); 8.12 (d, J=1.37 Hz, 2H); 6.82 (d, J=9.00 Hz, 1H); 3.78-3.86 (m, 7H); 3.11 (br. s., 2H); 3.12 (t, J=4.89 Hz, 2H); 2.84 (s, 3H).

Provenance & Evidence