Sodium Bicarbonate → ethyl 4-[1-(2-aminopyrimidin-4-yl)-3-methyl-1H-indazol-6-yl]-2-hydroxy-2-methylbut-3-ynoate

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Reaction Conditions

Reaction Steps

To a solution of 4-(6-iodo-3-methyl-1H-indazol-1-yl)pyrimidin-2-amine (170 mg, 0.38 mmol) in dry THF (3 mL) was introduced bis(triphenylphosphine)palladium(II) chloride (27 mg, 0.04 mmol), ethyl 2-hydroxy-2-methyl-4-(trimethylsilyl)but-3-ynoate (164 mg, 0.76 mmol) and TBAF (0.46 mL of a 1M solution in THF, 0.46 mmol). The solution was warmed to 50° C. for 1.5 hr. After cooling, sodium bicarbonate (4 mL of saturated aqueous NaHCO3) was introduced and the solution extracted with EtOAc (3×10 mL extractions). The combined organic extracts were washed with brine (10 mL), dried (Na2SO4), filtered and concentrated in vacuo. Purification by silica gel flash column chromatography (DCM containing a 1-10% gradient of methanol) furnished the title compound as an orange oil: 1H NMR (250 MHz, Chloroform-d) delta 1.39 (3H, t, J=7.1 Hz), 1.83 (3 H, s), 2.60 (3H, s), 4.38 (2H, q, J=7.1 Hz), 5.20 (2H, s), 7.29 (1H, s), 7.34 (1H, dd, J=8.2, 1.3 Hz), 7.60 (1H, dd, J=8.2, 0.7 Hz), 8.29 (1H, d, J=5.7 Hz), 8.83 (1H, s); LC-MS: m/z=+366.05 (M+H)+.

Provenance & Evidence