Sulfuric Acid → 2,6-Difluoro-N-{1-[(5-hydroxy-2-methylphenyl)methyl]-1H-pyrazol-3-yl}benzamide

HRID 1946347노트

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HRID 1946347 반응식
N[C:2]1[CH:3]=[CH:4][C:5]([CH3:25])=[C:6]([CH2:8][N:9]2[CH:13]=[CH:12][C:11]([NH:14][C:15](=[O:24])[C:16]3[C:21]([F:22])=[CH:20][CH:19]=[CH:18][C:17]=3[F:23])=[N:10]2)[CH:7]=1.S(=O)(=O)(O)[OH:27].N([O-])=O.[Na+].NC(N)=O>O.S([O-])([O-])(=O)=O.[Cu+2].C(OCC)(=O)C>[F:23][C:17]1[CH:18]=[CH:19][CH:20]=[C:21]([F:22])[C:16]=1[C:15]([NH:14][C:11]1[CH:12]=[CH:13][N:9]([CH2:8][C:6]2[CH:7]=[C:2]([OH:27])[CH:3]=[CH:4][C:5]=2[CH3:25])[N:10]=1)=[O:24]

참가 물질

8

반응물 4

HCID 1118Sulfuric AcidHCID 1176UreaHCID 23668193Sodium NitriteHCID 59548012N-{1-[(5-amino-2-methylphenyl)methyl]-1H-pyrazol-3-yl}-2,6-difluorobenzamide

생성물 1

HCID 595478422,6-Difluoro-N-{1-[(5-hydroxy-2-methylphenyl)methyl]-1H-pyrazol-3-yl}benzamide

시약·촉매·용매 3

HCID 24462Copper Sulfate촉매HCID 962Water용매3회HCID 8857Ethyl Acetate용매

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온도
2.5 °C

실험 절차

To N-{1-[(5-amino-2-methylphenyl)methyl]-1H-pyrazol-3-yl}-2,6-difluorobenzamide (for a preparation see Intermediate 48) (0.312 g, 0.911 mmol) in an ice-water bath was added sulphuric acid specific gravity 1.84 (3 ml, 56.3 mmol). To the stirred suspension was slowly added water (5 ml). To the slight suspension was added a solution of sodium nitrite (0.132 g, 1.91 mmol, Aldrich) in water (1 ml). The solution was maintained at 0-5° C. for 20 min. To the solution was added urea (0.350 g, 5.83 mmol, Aldrich) and then copper (II) sulphate (50 mg, 0.313 mmol, Fluka). The mixture was heated to 90° C. for 30 min. The mixture was allowed to stand at ambient temperature overnight. The mixture was diluted with water (100 ml) and then ethyl acetate (50 ml). The phases were separated and the aqueous phase extracted with ethyl acetate (25 ml). The combined organic extracts were concentrated in vacuo to leave a brown gum (0.3 g). The residue was loaded in dichloromethane and purified on silica 50 g using 0-100% ethyl acetate-cyclohexane. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a yellow foam (206 mg); LCMS (System 4) MH+=344, tRET=2.36 min.

후처리

  1. temperatureThe mixture was heated to 90° C. for 30 min
  2. customThe phases were separated
  3. extractionthe aqueous phase extracted with ethyl acetate (25 ml)
  4. concentrationThe combined organic extracts were concentrated in vacuo

출처 및 근거

ORD 기록
ord-0e072480a1f74f628f679e1971c95af7
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08399436B2

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