Sodium hydride → 2-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine

Temperature

0 °C

In a dry round-bottomed flask, 2-bromo-5H-pyrrolo[2,3-b]pyrazine (5.0 g, 25.2 mmol) was dissolved in DMF (50 mL). The reaction mixture was cooled to 0° C. and sodium hydride (60% dispersion in mineral oil, 1.22 g, 30.6 mmol). The reaction mixture was warmed to room temperature and stirred for 15 min then cooled back to 0° C. and SEM-Cl (5.4 mL, 30.4 mmol) was slowly added. After the addition was complete, the ice bath was removed and the reaction mixture was stirred at room temperature for 1.5 h. The reaction mixture was quenched with 50 mL water and extracted with 150 mL diethyl ether (2×). The combined organic layers were washed twice with 30 mL water and once with 30 mL brine then dried over sodium sulfate, filtered and concentrated. The residue was absorbed on ˜20 g SiO2 and chromatographed over 200 g SiO2 with EtOAc/Hexanes (gradient: 0-15% EtOAc). All fractions containing product were combined and concentrated to afford 6.61 g (80%) of 2-bromo-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine as a pale yellow oil which gradually solidified. 1H NMR (CDCl3, 300 MHz): δ (ppm) 8.38 (s, 1H), 7.70 (d, J=3.8 Hz, 1H), 6.76 (d, J=3.8 Hz, 1H), 5.68 (s, 2H), 3.50-3.65 (m, 2H), 0.88-1.03 (m, 2H), 0.00 (s, 9H).

1. temperatureThe reaction mixture was warmed to room temperature
2. temperaturethen cooled back to 0° C.
3. additionAfter the addition
4. customthe ice bath was removed
5. stirringthe reaction mixture was stirred at room temperature for 1.5 h
6. customThe reaction mixture was quenched with 50 mL water
7. extractionextracted with 150 mL diethyl ether (2×)
8. washThe combined organic layers were washed twice with 30 mL water and once with 30 mL brine
9. dry with materialthen dried over sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated
12. customThe residue was absorbed on ˜20 g SiO2
13. customchromatographed over 200 g SiO2 with EtOAc/Hexanes (gradient: 0-15% EtOAc)
14. additionAll fractions containing product
15. concentrationconcentrated

ORD record

ord-5922654dd55042f5b54b846c2e736319

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08658646B2