Sodium hydride → 3-Ethyl-5-trifluoromethyl-pyrrolo[3,2-b]pyridin-1-ylamine

HRID 2382070ノート

反応式

HRID 2382070 の反応式
[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]

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 685552481H-Pyrrolo[3,2-b]pyridine, 3-ethyl-5-(trifluoromethyl)-

生成物 1

HCID 685552233-Ethyl-5-trifluoromethyl-pyrrolo[3,2-b]pyridin-1-ylamine収率 84.4%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
0 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-9d1139f37b194225841ada225f2b0194
出典データセット
uspto-grants-2012_09
特許番号
US08258130B2

反応ノート

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