Benzaldehyde → 5-Methoxy-3-(2-phenyl-1H-imidazol-1-yl)-1-[3-(trifluoromethyl)phenyl]pyridazin-4(1H)-one

HRID 1895310노트

반응식

HRID 1895310 반응식
[NH2:1][C:2]1[C:7](=[O:8])[C:6]([O:9][CH3:10])=[CH:5][N:4]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:20])([F:19])[F:18])[CH:12]=2)[N:3]=1.[CH:21]([CH:23]=O)=O.[CH:25](=O)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.[NH4+:33].[Cl-].OP(O)(O)=O>CO.O.C([O-])(O)=O.[Na+]>[CH3:10][O:9][C:6]1[C:7](=[O:8])[C:2]([N:1]2[CH:23]=[CH:21][N:33]=[C:25]2[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[N:3][N:4]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:18])([F:20])[F:19])[CH:12]=2)[CH:5]=1

참가 물질

9

반응물 5

HCID 240BenzaldehydeHCID 1004Phosphoric AcidHCID 7860GlyoxalHCID 25517Ammonium ChlorideHCID 59436209HCID 59436209, 화합물

생성물 1

HCID 580722075-Methoxy-3-(2-phenyl-1H-imidazol-1-yl)-1-[3-(trifluoromethyl)phenyl]pyridazin-4(1H)-one수율 29.1%

시약·촉매·용매 3

HCID 887Methanol용매HCID 962Water용매HCID 516892Sodium Bicarbonate용매

실험 절차

A solution of 3-amino-5-methoxy-1-[3-(trifluoromethyl)phenyl]pyridazin-4(1H)-one (300 mg, 1.05 mmol) and glyoxal (40% solution, 0.240 mL, 2.10 mmol) in MeOH (3 mL) was stirred at room temperature for 24 h. To the solution were added benzaldehyde (0.428 mL, 4.21 mmol) and NH4Cl (225 mg, 4.21 mmol). The mixture was heated to reflux for 2 h. To the mixture was added H3PO4 (0.142 mL). The mixture was heated to reflux for 20 h. The mixture was diluted with water and saturated NaHCO3 aqueous solution, extracted with AcOEt, dried over Na2SO4, filtered, concentrated in vacuo, purified by column chromatography on basic silica gel (hexane/AcOEt=50/50 to 0/100) and by HPLC and recrystallized with AcOEt/hexane to yield the title compound (126 mg, 29% yield) as a white solid: mp 167-170° C. 1H NMR (DMSO-d6, 300 MHz): δ ppm 3.94 (3H, s), 7.19 (1H, d, J=1.5 Hz), 7.31-7.49 (5H, m), 7.61 (1H, d, J=1.5 Hz), 7.68-7.91 (4H, m), 8.80 (1H, s). Anal. Calcd for C21H15F3N4O2.0.7H2O: C, 59.35; H, 3.89; N, 13.18. Found: C, 59.28; H, 3.69; N, 13.12.

후처리

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 2 h
  3. temperatureThe mixture was heated
  4. temperatureto reflux for 20 h
  5. extractionextracted with AcOEt
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. custompurified by column chromatography on basic silica gel (hexane/AcOEt=50/50 to 0/100) and by HPLC
  10. customrecrystallized with AcOEt/hexane

출처 및 근거

ORD 기록
ord-c7b403d4ba524e5591882f986a81d589
출처 데이터셋
uspto-grants-2013_08
특허 번호
US08513251B2

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