3,5-Bis(trifluoromethyl)benzyl bromide → Imnopitant

HRID 1017431

Reaktionsgleichung

Reaktionsgleichung von HRID 1017431
[CH3:1][NH:2][C:3](=[O:24])[C:4]1[C:9]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[CH3:16])=[CH:8][C:7]([N:17]2[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]2)=[N:6][CH:5]=1.C[Si](C)(C)[N-][Si](C)(C)C.[K+].[F:35][C:36]([F:50])([F:49])[C:37]1[CH:38]=[C:39]([CH:42]=[C:43]([C:45]([F:48])([F:47])[F:46])[CH:44]=1)[CH2:40]Br>O1CCCC1>[F:35][C:36]([F:50])([F:49])[C:37]1[CH:38]=[C:39]([CH:42]=[C:43]([C:45]([F:48])([F:47])[F:46])[CH:44]=1)[CH2:40][N:2]([CH3:1])[C:3](=[O:24])[C:4]1[C:9]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[CH3:16])=[CH:8][C:7]([N:17]2[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]2)=[N:6][CH:5]=1

Komponenten

5

Edukt 3

HCID 1225733,5-Bis(trifluoromethyl)benzyl bromideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 15481065N-methyl-6-(4-methyl-piperazin-1-yl)-4-o-tolyl-nicotinamide

Produkt 1

HCID 9808518ImnopitantAusbeute 75 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

To a solution of 750 mg (2.32 mmol) N-methyl-6-(4-methyl-piperazin-1-yl)-4-o-tolyl-nicotinamide in 16 ml tetrahydrofuran, 3 ml of a 1 M solution (3 mmol) of potassium hexamethyldisilazide in tetrahydrofuran was added at room temperature. After 1 h, 0.43 ml (2.3 mmol) 3,5-bis(trifluoromethyl)benzyl bromide was added dropwise to the resulting suspension. The reaction was quenched with water after 1 h and the mixture was extracted with three 20 ml portions of ethyl acetate. The combined organic extracts were washed with saturated aqueous sodium chloride solution, dried with sodium sulfate and concentrated. Column chromatography gave 950 mg (74%) N-(3,5-bis-trifluoromethyl-benzyl)-N-methyl-6-(4-methyl-piperazin-1-yl)-4-o-tolyl-nicotinamide. The white foam was dissolved in a small amount of diethyl ether and treated with 2 ml 3 N hydrochloric acid solution in diethyl ether. Concentration afforded 1.02 g (74%) of the title compound as a white solid.

Aufarbeitung

  1. customThe reaction was quenched with water after 1 h
  2. extractionthe mixture was extracted with three 20 ml portions of ethyl acetate
  3. washThe combined organic extracts were washed with saturated aqueous sodium chloride solution
  4. dry with materialdried with sodium sulfate
  5. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-f3a703314626422f9f21e7556ec249e7
Quelldatensatz
uspto-grants-2002_11
Patentnummer
US06479483B2

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