Dichloromethane → 1-[(4-Methoxy)phenyl]-3-(trifluoromethyl)-4-(ethoxycarbonyl)-5-(2-furyl)pyrazole

HRID 2186254노트

반응식

HRID 2186254 반응식
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:13]([C:14]([OH:16])=O)=[C:12]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:11]([C:22]([F:25])([F:24])[F:23])=[N:10]2)=[CH:5][CH:4]=1.[C:26](Cl)(=O)[C:27](Cl)=O.[CH2:32](Cl)Cl>CN(C)C=O.CN(C)C1C=CN=CC=1.C(OCC)(=O)C>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:13]([C:14]3[O:16][CH:32]=[CH:26][CH:27]=3)=[C:12]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:11]([C:22]([F:23])([F:25])[F:24])=[N:10]2)=[CH:5][CH:4]=1

참가 물질

7

반응물 3

HCID 6344DichloromethaneHCID 65578Oxalyl chlorideHCID 179399451-[(4-Methoxy)phenyl]-3-(trifluoromethyl)-4-(ethoxycarbonyl)-pyrazole-5-carboxylic acid

생성물 1

HCID 179399581-[(4-Methoxy)phenyl]-3-(trifluoromethyl)-4-(ethoxycarbonyl)-5-(2-furyl)pyrazole수율 70%

시약·촉매·용매 3

HCID 6228Dimethylformamide촉매HCID 142844-(Dimethylamino)pyridine촉매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of 1-[(4-methoxy)phenyl]-3-(trifluoromethyl)-4-(ethoxycarbonyl)-pyrazole-5-carboxylic acid (0.5 g, 1.4 mmol) in 10 mL of methylene chloride was added oxalyl chloride (0.18 mL, 2.1 mmol) and 2 drops of dimethylformamide. The reaction was stirred at ambient temperature for 6 h and then the volatiles were removed in vacuo. The residue was dissolved in 20 mL of methylene chloride and then there was added 4-dimethylaminopyridine (0.51 g, 4.2 mmol). The reaction was stirred for 10 min and then there was added (2′-methylsulfonyl-3-fluoro-[1,1′]-biphen-4-yl)amine hydrochloride (0.42 g, 1.4 mmol). The resulting mixture was allowed to stir at ambient temperature for 16 h. The reaction was diluted with ethyl acetate and the organics were washed with 10% aq HCl, sat'd aq NaHCO3 and brine, dried (MgSO4), filtered through a pad of silica gel and concentrated to afford 0.6 g (70%) of the compound of EXAMPLE 169 as a solid. A portion was purified by prep HPLC (C18 reverse phase column, elution with a H2O/CH3CN gradient with 0.5% TFA) and lyophilized to afford the title compound as a white powder. LRMS (ES+): 628.1 (M+Na)+.

후처리

  1. customthe volatiles were removed in vacuo
  2. dissolutionThe residue was dissolved in 20 mL of methylene chloride
  3. stirringThe reaction was stirred for 10 min
  4. stirringto stir at ambient temperature for 16 h
  5. washthe organics were washed with 10% aq HCl
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered through a pad of silica gel
  8. concentrationconcentrated

출처 및 근거

ORD 기록
ord-38e2f264403944458ce8f4a0e5b1cf1e
출처 데이터셋
uspto-grants-2002_06
특허 번호
US06403620B1

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