Sodium hydride → HCID 86762623, compound

Participants

Reaction Steps

To a stirred mixture of sodium hydride (12.5 g, 520 mmol, 60% in mineral oil) in anhydrous THF (300 mL) at 0° C. was added dropwise 2-chloro-5H-pyrrolo[3,2-d]pyrimidine (40.0 g, 262 mmol) dissolved in anhydrous THF (200 mL). The reaction mixture was stirred at 0° C. for 15 min them SEMCl (52.5 g, 315 mmol) was added dropwise. The mixture was then stirred at RT for 1 h and then diluted with EtOAc. The organic layer was washed with water and brine, dried over (Na2SO4), filtered and concentrated under reduced pressure. The crude product was purified by SiO2 chromatography to afford 42 g (56.4%) of 2-chloro-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[3,2-d]pyrimidine as an orange oil. A high-pressure tube charged with 2-chloro-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[3,2-d]pyrimidine (2.23 g, 7.90 mmol), tributyl(1-ethoxyvinyl)stannane (3.7 g, 10.27 mmol), and Pd(PPh3)2Cl2 (200 mg) in degassed DMF (20 mL) under N2 was sealed and heated at 100° C. for 16 h. The reaction mixture was cooled, diluted with EtOAc, and filtered through a pad of Celite® to remove Pd solid. The filtrate was washed with water and brine, dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude product was dissolved in anhydrous THF (0.3 M), and 2N HCl (5.0 eq.) was added. The reaction mixture was stirred at RT under N2 for 16 h, poured into 10% aq. NaOH solution, and then extracted with EtOAc. The organic layer was washed with water and brine, dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude product was purified by SiO2 chromatography to afford 1.5 g (66%) of 1-(5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[3,2-d]pyrimidin-2-yl)ethanone as pale yellow solid. 1H NMR (400 MHz, CDCl3) δ 9.09 (s, 1H), 7.66 (d, J=3.2 Hz, 1H), 6.89 (d, J=4.8 Hz, 1H), 5.60 (s, 2H), 3.49 (t, J=8.0 Hz, 2H), 2.88 (s, 3H), 0.901 (t, J=8.0 Hz, 2H), −0.053 (s, 9H); MS (ESI) m/z: 291 [M+].

Provenance & Evidence