反应详情

温度

0 °C

A suspension of NaH (4.65 g, 116 mmol, 60% in mineral oil) in DMF (40 mL) at 0° C. is treated with 3-ethyl-5-trifluoromethyl-1H-pyrrolo[3,2-b]pyridine (2 g, 7.75 mmol) and stirred at 0° C. for 1 h. The mixture is treated with HOSA (4.4 g, 38.8 mmol) portion wise and warmed to rt over 2 h. The mixture is then poured over ice, treated with solid NH4Cl (3 g), and filtered through a pad of Celite. The filtrate is extracted with Et2O (3×150 mL). The combined organic layer is dried (Na2SO4), filtered and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 30%-50% EtOAc in heptane to afford 3-ethyl-5-trifluoromethyl-pyrrolo[3,2-b]pyridin-1-ylamine (1.5 g, 84%). MS: 230 (M+H); 1H NMR (300 MHz, DMSO-d6): δ 7.97 (d, 1H), 7.59 (d, 1H), 7.54 (s, 1H), 6.12 (s, NH2, 2H), 2.78 (q, 2H), 1.28 (t, 3H).

1. additionThe mixture is treated with HOSA (4.4 g, 38.8 mmol) portion wise
2. temperaturewarmed to rt over 2 h
3. additionThe mixture is then poured over ice
4. filtrationfiltered through a pad of Celite
5. extractionThe filtrate is extracted with Et2O (3×150 mL)
6. dry with materialThe combined organic layer is dried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe residue is purified by silica gel chromatography
10. washeluting with 30%-50% EtOAc in heptane