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

HRID 2075052Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2075052
[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

Komponenten

6

Edukt 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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideKatalysatorHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

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.

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-52643f1367364f27ad2b58f28933ca40
Quelldatensatz
uspto-grants-2011_04
Patentnummer
US07919506B2

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