Ethyl Acetate → tert-butyl 3-(9-isopropyl-6((1-methyl-1H-pyrazol-4-yl)amino)-9H-purin-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-chloro-9-isopropyl-N-(1-methyl-1H-pyrazol-4-yl)-9H-purin-6-amine (600 mg, 2 mmol), as prepared in step 1 of Example 2, tert-butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate (700 mg, 2.3 mmol, 1.1 mol eq), tripotassium phosphate (1.11 g, 5.1 mmol, 2.5 mol eq), PdCl2(dppf) (75 mg, 0.1 mmol, 0.05 mol eq) in dioxane (10 mL) and water (5 mL) was degassed, stirred and heated at 80° C. (using microwave at normal absorption level) for 30 min. The reaction was then diluted with ethyl acetate (120 mL), washed with brine (20 mL), dried over Na2SO4 and evaporated to give a residue that was purified via flash chromatography with gradients from 50% ethyl acetate-50% heptane to 100% ethyl acetate and then to 10% ammonia (7 N in methanol)-90% ethyl acetate to give the title product as a red solid (901 mg, 100% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.89 (s, 1 H) 8.29 (s, 1 H) 8.00 (br. s., 1 H) 7.79 (br. s., 1 H) 7.22 (br. s., 1 H) 4.77 (dt, J=13.39, 6.76 Hz, 1 H) 4.45 (br. s., 2 H) 3.84 (s, 3 H) 3.50 (t, J=5.38 Hz, 2 H) 2.36 (d, J=3.18 Hz, 2 H) 1.57 (d, J=6.72 Hz, 6 H) 1.44 (s, 9 H). m/z (APCI+) for C22H30N8O2 439.3 (M+H)+.

Provenance & Evidence