Phosphine, tris(4-methoxyphenyl)- → (R)-2-(1-(4-amino-3-(3-fluoro-4-morpholinophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-5-fluoro-3-(3-fluorophenyl)-4H-chromen-4-one

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This example is also described in Example 59 of WO 2012/151525. To a solution of 3-(3-fluoro-4-morpholinophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.080 g, 0.254 mmol) in THF (2 ml), tris(4-methoxyphenyl)phosphine (0.134 g, 0.381 mmol) and diisopropylazodicarboxylate (0.07 ml, 0.381 mmol) is added and stirred at room temperature (RT) for 10 minutes. To this mixture (−)-5-fluoro-3-(3-fluorophenyl)-2-(1-hydroxyethyl)-4H-chromen-4-one (0.077 g, 0.254 mmol) is added and stirred for 12 h. The reaction mixture is diluted with water and extracted with ethyl acetate. The organic layer is dried over sodium sulphate and concentrated under reduced pressure. The crude product is purified by column chromatography with methanol:dichloromethane to afford the title compound as an off-white solid. MP: 242-245° C. Enantiomeric excess: 96.21% Mass: 599.1 (M++1).

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