Diisopropylamine → tert-butyl 5-cyclopropyl-3-(2-phenyl-5-((trimethylsilyl)ethynyl)pyrimidin-4-ylamino)-1H-pyrazole-1-carboxylate

Participants

Reaction Steps

Under nitrogen, to the mixture of tert-butyl 5-cyclopropyl-3-(5-iodo-2-phenylpyrimidin-4-ylamino)-1H-pyrazole-1-carboxylate (245 mg, 0.49 mmol, 1.0 equiv), PdCl2(PPh3)2 (40 mg, 0.057 mmol, 0.12 equiv.), CuI (22 mg, 0.115 mmol, 0.23 equiv.), i-Pr2NH (1.7 mL, 11.78 mmol, 24 equiv.) and THF (10 mL), TMS-acetylene (3.5 mL, 25 mmol, 51 equiv.) were added. After stirring at r.t. for 2 h, silica gel was added to the reaction mixture and the solvents were removed. The residue was purified by silica gel chromatography (hexane/EtOAc=3:1 as eluant) afford tert-butyl 5-cyclopropyl-3-(2-phenyl-5-((trimethylsilyl)ethynyl) pyrimidin-4-ylamino)-1H-pyrazole-1-carboxylate (276 mg, 98%). LC-MS (m/z): 474.2 [M+H]+. To the solution of tert-butyl 5-cyclopropyl-3-(2-phenyl-5-((trimethylsilyl)ethynyl)pyrimidin-4-ylamino)-1H-pyrazole-1-carboxylate (276 mg, 0.58 mmol, 1 equiv.) in CH2Cl2 (2 mL) was added TFA (2 mL). After 10 min at rt, the reaction mixture was concentrated to generate crude N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-phenyl-5-((trimethylsilyl)ethynyl)pyrimidin-4-amine, which was used in next step without further purification. LC-MS (m/z): 374.2 [M+H]+.

Provenance & Evidence