p-Toluenesulphonyl cyanide → 2,4-Dichloro-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile

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Reaction Conditions

Reaction Steps

To a solution of LiCl (dry, 5.3 g, 126 mmol) in THF (150 mL) was added iPrMgCl (63 mL of 2 M in THF, 126 mmol). After stirring for 15 min, the mixture was cooled to −78° C. and 2,4-dichloro-5-iodo-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (31 g, 4.5 mmol) was added dropwise as a solution in THF (50 mL). After stirring for 20 min, a solution of tosyl cyanide (19.8 g, 100 mmol) in THF (50 mL) was added dropwise. The mixture was stirred at −78° C. for 30 min. The reaction was quenched with HOAc (20 mL) and after stirring at −78° C. for 15 min, water (200 mL) and EtOAc (200 mL) were added. The organic layer was separated, and the aqueous layer was further extracted with EtOAc (two×150 mL). The combined organic extracts were washed with brine, dried over MgSO4 and concentrated in vacuo to give the crude product. After sitting as a concentrate in EtOAc overnight, crystals formed which were collected to afford 3.8 grams 90% purity by 1H NMR. The filtrate was purified via flash chromatography to afford the title compound (12 g). The combined yield was 15.8 grams (66% yield) as a white solid. 1H NMR (400 MHz, chloroform-d) 0.00 (s, 9H), 0.91-1.01 (m, 2H), 3.53-3.66 (m, 2H), 5.65 (s, 2H), 7.94 (s, 1H).

Provenance & Evidence