Hydrochloric Acid → (3R)-tert-butyl 3-(6-(5-(2-(cyclopropylamino)pyrimidin-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yloxy)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

A mixture of (3R)-tert-butyl 3-(6-(5-(2-chloropyrimidin-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yloxy)piperidine-1-carboxylate (172 mg, 0.290 mmol), cyclopropylamine (0.12 mL, 1.74 mmol) and DIPEA (0.25 mL, 1.45 mmol) in THF (1.5 mL) was stirred and heated in a Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 120° C. for 30 min and heated at 140° C. for an additional 1 h. 1 M HCl (aq.) was added and the mixture was extracted with EtOAc (3×). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated. The crude was purified by silica gel chromatography, eluting with a gradient of 0-50% EtOAc in hexanes, to provide (3R)-tert-butyl 3-(6-(5-(2-(cyclopropylamino)pyrimidin-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yloxy)piperidine-1-carboxylate (116 mg, 0.19 mmol, 65% yield) as a clear oil. MS (ESI, pos. ion) m/z: 613.3 (M+1).

Provenance & Evidence