5-((Diphenylmethylene)amino)-N-methoxy-N-methylnicotinamide → [7-(2-{[tert-Butyl(dimethyl)silyl]oxy}-1,1-dimethylethyl)-2-chloro-7H-pyrrolo[2,3-d]pyrimidin-5-yl]{5-[(diphenylmethylene)amino]pyridin-3-yl}methanone

Participants

Reaction Conditions

Reaction Steps

Isopropyl magnesium chloride (105 mL, 210 mmol, 2.0 M in THF) was added to 7-(2-{[tert-butyl(dimethyl)silyl]oxy}-1,1-dimethylethyl)-2-chloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidine (89.0 g, 190 mmol) (see Preparation 44) in THF (450 mL) at 0° C., under nitrogen. The mixture was stirred at 0° C. for 1 hour then a solution of 5-[(diphenylmethylene)amino]-N-methoxy-N-methylnicotinamide (72.6 g, 210 mmol) (see Preparation 23) in THF (200 mL) was added dropwise at 0° C. The mixture was warmed to room temperature and stirred at this temperature for 16 hours. The reaction mixture was quenched with 10% aqueous ammonium chloride (500 mL) and the organic phase was separated. The aqueous phase was extracted with ethyl acetate (2×300 mL). The combined organic extracts were washed with brine (400 mL), dried over sodium sulfate, evaporated in vacuo and the crude material was purified by column chromatography on silica gel (gradient of heptane:EtOAc 100:0 to 60:40) to afford the title compound as a colourless gum in 66% yield, 78.9 g.

Provenance & Evidence