Binap, (A+-)- → US10266548, Example 27-1

Participants

Reaction Steps

1 g of 5-methoxy-2-[1-(4-methoxybenzyl)-1H-indazol-3-yl]pyrimidin-4-amine (1-4-1, 2.77 mmol, 1. eq.), 938 mg of 4-bromo-3-(trifluoromethyl)pyridine (4.15 mmol, 1.5 eq.), 127 mg of Tris(dibenzylideneacetone)dipalladium (0) (0.138 mmol, 0.05 eq.), 345 mg of 1,1′-binaphthalene-2,2′-diylbis(diphenylphosphane) (0.553 mmol, 0.2 eq), 1.06 g of sodium 2-methylpropan-2-olate (97%) (11.1 mmol, 4 eq.) and 15 ml of N,N-dimethylformamide were stirred under nitrogen atmosphere for 24 hours at 100° C. bath temperature in a pressure pipe. The reaction mixture was washed with half-saturated aqueous ammonium chloride solution. The organic layer was extracted three times with dichloromethane. The combined organic layers were washed with brine and dried over magnesium sulfate and concentrated in vacuo. The residue was purified twice by flash chromatography (hexane/ethyl acetate/methanol) and preparative TLC. A crystallisation gave 56.9 mg (0.1 mmol, 3.73%) of the analytically pure target compound.

Provenance & Evidence