Iodoethane → (3,5-Bis-trifluoromethyl-benzyl)-{2-[ethoxy-(tetrahydro-pyran-4-yl)-methyl]-5-trifluoromethyl-benzyl}-(2-methyl-2H-tetrazol-5-yl)-amine

HRID 2075052노트

반응식

HRID 2075052 반응식
[F:1][C:2]([F:41])([F:40])[C:3]1[CH:4]=[C:5]([CH:33]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:35]=1)[CH2:6][N:7]([CH2:14][C:15]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[CH:17][C:16]=1[CH:25]([CH:27]1[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1)[OH:26])[C:8]1[N:9]=[N:10][N:11]([CH3:13])[N:12]=1.[H-].[Na+].I[CH2:45][CH3:46]>C1COCC1.CN(C=O)C>[F:41][C:2]([F:40])([F:1])[C:3]1[CH:4]=[C:5]([CH:33]=[C:34]([C:36]([F:39])([F:37])[F:38])[CH:35]=1)[CH2:6][N:7]([CH2:14][C:15]1[CH:20]=[C:19]([C:21]([F:22])([F:23])[F:24])[CH:18]=[CH:17][C:16]=1[CH:25]([O:26][CH2:45][CH3:46])[CH:27]1[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1)[C:8]1[N:9]=[N:10][N:11]([CH3:13])[N:12]=1

참가 물질

6

반응물 3

HCID 6340IodoethaneHCID 24758Sodium hydrideHCID 58968611(2-(((3,5-bis(trifluoromethyl)benzyl)(2-methyl-2H-tetrazol-5-yl)amino)methyl)-4-(trifluoromethyl)phenyl)(tetrahydro-2H-pyran-4-yl)methanol

생성물 1

HCID 58968677(3,5-Bis-trifluoromethyl-benzyl)-{2-[ethoxy-(tetrahydro-pyran-4-yl)-methyl]-5-trifluoromethyl-benzyl}-(2-methyl-2H-tetrazol-5-yl)-amine수율 54%

시약·촉매·용매 2

HCID 6228Dimethylformamide촉매HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of (2-(((3,5-bis(trifluoromethyl)benzyl)(2-methyl-2H-tetrazol-5-yl)amino)methyl)-4-(trifluoromethyl)phenyl)(tetrahydro-2H-pyran-4-yl)methanol (20.4 mg, 0.034 mmo) in THF (0.15 mL) at 0° C. was added sodium hydride (60% dispersion in mineral oil, 4.1 mg, 0.10 mmol). The mixture was stirred at room temperature for 30 minutes, recooled to 0° C. and DMF (5 drops) was added followed by iodoethane (8 μL, 0.10 mmol). The mixture was stirred at room temperature overnight. Solvent was removed in vacuo. The residue was purified by chromatography over 12+S Biotage silica column (eluted with 0-30% ethyl acetate in hexanes) to afford the title compound (11.5 mg, 54%). 1H NMR (400 MHz, CDCl3) δ ppm 1.0 (m, 1H) 1.1 (t, J=7.1 Hz, 3H) 1.4(m, 2H) 1.7(m, 1H) 1.8(d, J=13.3 Hz, 1H) 3.2 (m, 4H) 3.9 (dd, J=11.6, 3.3 Hz, 1H) 4.0 (dd, J=11.4, 3.9 Hz, 1H) 4.2 (s, 3H) 4.2 (d, J=7.1 Hz, 1H) 4.7 (d, J=13.3 Hz, 1H) 4.7 (s, 2H) 4.9 (d, J=15.8 Hz, 1H) 7.3 (s, 1H) 7.6 (m, 2H) 7.6 (s, 2H) 7.8 (s, 1H). MS (ES+) Calc: 625.2, Found: 626.4 (M+1) According to the procedure described in example 33 and using the appropriate secondary alcohol and alkylating reagent, examples 34-40 were prepared.

후처리

  1. customrecooled to 0° C.
  2. stirringThe mixture was stirred at room temperature overnight
  3. customSolvent was removed in vacuo
  4. customThe residue was purified by chromatography over 12+S Biotage silica column (eluted with 0-30% ethyl acetate in hexanes)

출처 및 근거

ORD 기록
ord-52643f1367364f27ad2b58f28933ca40
출처 데이터셋
uspto-grants-2011_04
특허 번호
US07919506B2

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