Sodium hydride → 3-Ethyl-5-trifluoromethyl-pyrrolo[3,2-b]pyridin-1-ylamine
Reaction equation
[H-].[Na+].[CH2:3]([C:5]1[C:9]2=[N:10][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:12][CH:13]=[C:8]2[NH:7][CH:6]=1)[CH3:4].[NH4+:18].[Cl-]>CN(C=O)C>[CH2:3]([C:5]1[C:9]2=[N:10][C:11]([C:14]([F:16])([F:17])[F:15])=[CH:12][CH:13]=[C:8]2[N:7]([NH2:18])[CH:6]=1)[CH3:4]Participants
Conditions
- Temperature
- 0 °C
Procedure
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).
Workup
- additionThe mixture is treated with HOSA (4.4 g, 38.8 mmol) portion wise
- temperaturewarmed to rt over 2 h
- additionThe mixture is then poured over ice
- filtrationfiltered through a pad of Celite
- extractionThe filtrate is extracted with Et2O (3×150 mL)
- dry with materialThe combined organic layer is dried (Na2SO4)
- filtrationfiltered
- concentrationconcentrated in vacuo
- customThe residue is purified by silica gel chromatography
- washeluting with 30%-50% EtOAc in heptane
Sources & evidence
- ORD record
- ord-9d1139f37b194225841ada225f2b0194
- Source dataset
- uspto-grants-2012_09
- Patent number
- US08258130B2
Reaction notes
Loading…