Dimethylformamide → 3-{[[(2-Cyclohexyl-methoxy-methyl)-5-trifluoromethyl-benzyl]-(2-methyl-2H-tetrazol-5-yl)-amino]-methyl}-5-trifluoromethyl-benzonitrile

HRID 2075073

反応式

HRID 2075073 の反応式
C1(C(OC)[C:8]2[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][C:9]=2[CH2:10][NH:11][C:12]2[N:13]=[N:14][N:15]([CH3:17])[N:16]=2)CCCCC1.[H-].[Na+].Br[CH2:31][C:32]1[CH:33]=[C:34]([CH:37]=[C:38]([C:40]([F:43])([F:42])[F:41])[CH:39]=1)[C:35]#[N:36].CN([CH:47]=[O:48])C>>[CH2:8]1[CH2:21][CH2:20][CH2:19][CH2:18][CH:9]1[CH:10]([CH:10]([N:11]([CH2:31][C:32]1[CH:33]=[C:34]([CH:37]=[C:38]([C:40]([F:43])([F:42])[F:41])[CH:39]=1)[C:35]#[N:36])[C:12]1[N:13]=[N:14][N:15]([CH3:17])[N:16]=1)[C:9]1[CH:18]=[C:19]([C:22]([F:23])([F:25])[F:24])[CH:20]=[CH:21][CH:8]=1)[O:48][CH3:47]

参加物

5

反応物 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 116013693-(Bromomethyl)-5-(trifluoromethyl)benzonitrileHCID 58968679[2-(cyclohexyl-methoxy-methyl)-5-trifluoromethyl-benzyl]-(2-methyl-2H-tetrazol-5-yl)-amine

生成物 1

HCID 866150533-{[[(2-Cyclohexyl-methoxy-methyl)-5-trifluoromethyl-benzyl]-(2-methyl-2H-tetrazol-5-yl)-amino]-methyl}-5-trifluoromethyl-benzonitrile収率 49%

実験手順

To a solution of [2-(cyclohexyl-methoxy-methyl)-5-trifluoromethyl-benzyl]-(2-methyl-2H-tetrazol-5-yl)-amine (28 mg, 0.073 mmol) in DMF (2 mL) at 0° C. under nitrogen was added sodium hydride (4.4 mg, 0.11 mmol, 60% dispersion in mineral oil). The reaction was stirred for 30 minutes, allowing it to warm to room temperature. The reaction mixture was then treated with 3-(bromomethyl)-5-(trifluoromethyl)benzonitrile (19.3 mg, 0.073 mmol) at room temperature and stirred for overnight. Solvent was removed in vacuo. The residue was diluted with ethyl acetate and washed with satd. sodium bicarbonate solution, water and brine, dried over anhydrous magnesium sulphate and concentrated in vacuo. The product was purified on Biotage column (12+S), eluting with 2% ethyl acetate in heptane (1CV), 2-20% (10CV), 20% (2CV) to yield the title compound (21 mg, 49%) as a colorless oil, 1H NMR (400 MHz, CDCl3) δ ppm 1.07 (m, 4H) 1.2 (m, 3H) 1.65(m, 3H) 1.73 (m, 1H) 3.18 (s, 3H) 4.06 (s, 3H) 4.2 (m, 1H) 4.67-5.04 (m, 2H) 5.4 (m, 1H) 7.39 (s, 1H) 7.50 (m, 3H) 7.5 (m, 2H). MS (ES+) Calc: 566.2, Found: 567.5 (M+1). According to the procedures described in Examples 42-45 and using the appropriate amine, Examples 46-50 were prepared.

後処理

  1. stirringstirred for overnight
  2. customSolvent was removed in vacuo
  3. additionThe residue was diluted with ethyl acetate
  4. washwashed with satd
  5. dry with materialsodium bicarbonate solution, water and brine, dried over anhydrous magnesium sulphate
  6. concentrationconcentrated in vacuo
  7. customThe product was purified on Biotage column (12+S)
  8. washeluting with 2% ethyl acetate in heptane (1CV), 2-20% (10CV), 20% (2CV)

出典と根拠

ORDレコード
ord-c22af0ee1fc54a07879ff266d5c8be4f
出典データセット
uspto-grants-2011_04
特許番号
US07919506B2

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