Binap, (A+-)- → 4-({2-[1-(2-fluorobenzyl)-1H-indazol-3-yl]-5-methoxypyrimidin-4-yl}amino)pyridine-3-carbonitrile

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Reaction Steps

175 mg of 2-[1-(2-fluorobenzyl)-1H-indazol-3-yl]-5-methoxypyrimidin-4-amine (1-11-1, 0.501 mmol, 1. eq.), 101 mg of 4-bromopyridine-3-carbonitrile (0.551 mmol, 1.1 eq.), 115 mg of Tris(dibenzylideneacetone)dipalladium (0) (0.125 mmol, 0.25 eq.), 156 mg of 1,1′-binaphthalene-2,2′-diylbis(diphenylphosphane) (0.25 mmol, 0.5 eq), 144 mg of sodium 2-methylpropan-2-olate (97%) (1.503 mmol, 3 eq.) and 52 ml of N,N-dimethylformamide were stirred under nitrogen atmosphere for 30 minutes at 100° C. and 300 W in a CEM microwave. The reaction mixture was washed with half-saturated aqueous sodium chloride solution. The organic layer was extracted twice with ethyl acetate. The combined organic layers were washed with brine and dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography (hexane/dichloromethane/methanol) and preparative HPLC. A crystallisation from dichloromethane/methanol gave 5.8 mg (0.01 mmol, 2.6%) of the analytically pure target compound.

Provenance & Evidence