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

반응식

HRID 1257403 반응식
[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

참가 물질

9

반응물 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

생성물 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 acid수율 0.7%

시약·촉매·용매 4

HCID 180Acetone용매HCID 702Ethanol용매HCID 962Water용매HCID 21873804Tetrahydrofuran ethanol용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-492ba1a949bb40beb2d6002f80e1b6af
출처 데이터셋
uspto-grants-2013_06
특허 번호
US08461348B2

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