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

HRID 2075052Notes

Reaction equation

HRID 2075052 reaction equation
[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

Participants

6

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-52643f1367364f27ad2b58f28933ca40
Source dataset
uspto-grants-2011_04
Patent number
US07919506B2

Reaction notes

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