Methyl iodide → 1-[(4-{3-[2-(5-methyl-4H-1,2,4-triazol-3-yl)ethyl]-5-(trifluoromethyl)phenyl}-1,3-thiazol-2-yl)methyl]-1H-pyrazole-4-carboxylic acid

HRID 1257403

Reaktionsgleichung

Reaktionsgleichung von HRID 1257403
[NH2:1][C:2](=S)[CH2:3][CH2:4][C:5]1[CH:6]=[C:7]([C:15]2[N:16]=[C:17]([CH2:20][N:21]3[CH:25]=[C:24]([C:26]([O:28]CC)=[O:27])[CH:23]=[N:22]3)[S:18][CH:19]=2)[CH:8]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:10]=1.IC.[C:34]([NH:37][NH2:38])(=O)[CH3:35].[OH-].[Na+]>CC(C)=O.C(O)C.O.C(O)C.O1CCCC1>[CH3:35][C:34]1[NH:1][C:2]([CH2:3][CH2:4][C:5]2[CH:6]=[C:7]([C:15]3[N:16]=[C:17]([CH2:20][N:21]4[CH:25]=[C:24]([C:26]([OH:28])=[O:27])[CH:23]=[N:22]4)[S:18][CH:19]=3)[CH:8]=[C:9]([C:11]([F:12])([F:13])[F:14])[CH:10]=2)=[N:38][N:37]=1

Komponenten

9

Edukt 4

HCID 6328Methyl iodideHCID 14039AcetohydrazideHCID 14798Sodium HydroxideHCID 86650595ethyl 1-({4-[3-(3-amino-3-thioxopropyl)-5-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl}methyl)-1H-pyrazole-4-carboxylate

Produkt 1

HCID 1784340261-[(4-{3-[2-(5-methyl-4H-1,2,4-triazol-3-yl)ethyl]-5-(trifluoromethyl)phenyl}-1,3-thiazol-2-yl)methyl]-1H-pyrazole-4-carboxylic acidAusbeute 0,7 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 180AcetoneLösungsmittelHCID 702EthanolLösungsmittelHCID 962WaterLösungsmittelHCID 21873804Tetrahydrofuran ethanolLösungsmittel

Versuchsvorschrift

To a solution (3 mL) of the compound (300 mg, 0.64 mmol) obtained in Example 96c in acetone was added iodomethane (0.20 mL, 3.2 mmol), and the mixture was stirred at room temperature overnight. The solvent was evaporated under reduced pressure, and to a solution (4 mL) of the residue in ethanol was added acetylhydrazine (240 mg, 3.2 mmol), and the mixture was stirred at 80° C. for 6 hr. The solvent was evaporated under reduced pressure, and a solution (6 mL) of the residue in xylene was stirred at 150° C. overnight. The solvent was evaporated under reduced pressure, and to an ethanol/tetrahydrofuran mixed solution (v/v=1/1, 4 mL) of the residue was added 2N aqueous sodium hydroxide solution (0.45 mL, 0.91 mmol), and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, and the aqueous layer was washed with diethyl ether. The obtained aqueous layer was neutralized with 1N hydrochloric acid, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The resulting crude title compound was purified by HPLC and recrystallization (hexane-ethyl acetate) to give the title compound (2 mg, 0.7%) as colorless crystals.

Aufarbeitung

  1. customThe solvent was evaporated under reduced pressure
  2. stirringthe mixture was stirred at 80° C. for 6 hr
  3. customThe solvent was evaporated under reduced pressure
  4. stirringa solution (6 mL) of the residue in xylene was stirred at 150° C. overnight
  5. customThe solvent was evaporated under reduced pressure
  6. stirringthe mixture was stirred at room temperature overnight
  7. washthe aqueous layer was washed with diethyl ether
  8. extractionthe mixture was extracted with ethyl acetate
  9. washThe obtained organic layer was washed with saturated brine
  10. dry with materialdried over anhydrous sodium sulfate
  11. customThe solvent was evaporated under reduced pressure
  12. customThe resulting crude title compound was purified by HPLC and recrystallization (hexane-ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-492ba1a949bb40beb2d6002f80e1b6af
Quelldatensatz
uspto-grants-2013_06
Patentnummer
US08461348B2

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