Water → Methyl 4-({2-[4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]butanoyl}amino)-2,6-difluorobenzoate

HRID 56932

반응식

HRID 56932 반응식
C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.[Cl:19][C:20]1[CH:21]=[CH:22][C:23]([C:41]#[N:42])=[C:24]([C:26]2[C:31]([O:32][CH3:33])=[CH:30][N:29]([CH:34]([CH2:38][CH3:39])[C:35](O)=[O:36])[C:28](=[O:40])[CH:27]=2)[CH:25]=1.[NH2:43][C:44]1[CH:53]=[C:52]([F:54])[C:47]([C:48]([O:50][CH3:51])=[O:49])=[C:46]([F:55])[CH:45]=1.O>N1C=CC=CC=1.C(OCC)(=O)C>[Cl:19][C:20]1[CH:21]=[CH:22][C:23]([C:41]#[N:42])=[C:24]([C:26]2[C:31]([O:32][CH3:33])=[CH:30][N:29]([CH:34]([CH2:38][CH3:39])[C:35]([NH:43][C:44]3[CH:45]=[C:46]([F:55])[C:47]([C:48]([O:50][CH3:51])=[O:49])=[C:52]([F:54])[CH:53]=3)=[O:36])[C:28](=[O:40])[CH:27]=2)[CH:25]=1

참가 물질

7

반응물 4

HCID 962WaterHCID 111923Propylphosphonic anhydrideHCID 23001755Methyl 4-amino-2,6-difluorobenzoateHCID 1176225692-[4-(5-Chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]butanoic acid

생성물 1

HCID 117622814Methyl 4-({2-[4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]butanoyl}amino)-2,6-difluorobenzoate

시약·촉매·용매 2

HCID 1049Pyridine용매HCID 8857Ethyl Acetate용매

반응 조건

온도
90 °C

실험 절차

At 60-70° C., 110 μl (0.46 mmol, 4 eq.) of T3P (50% in ethyl acetate) were added dropwise to a solution of 46 mg (0.13 mmol) of 2-[4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]butanoic acid (racemate) and 51 mg (0.27 mmol, 2 eq.) of methyl 4-amino-2,6-difluorobenzoate in 1 ml of pyridine. The reaction mixture was heated to 90° C., stirred at 90° C. for 30 min and cooled to RT, and water and ethyl acetate were added. After phase separation, the aqueous phase was extracted with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried (sodium sulphate), filtered and concentrated under reduced pressure. The crude product was purified by normal phase chromatography (mobile phase: cyclohexane/ethyl acetate 10-50% mixtures). Yield: 54 mg (79% of theory)

후처리

  1. temperaturecooled to RT
  2. customAfter phase separation
  3. extractionthe aqueous phase was extracted with ethyl acetate
  4. washThe combined organic phases were washed with saturated aqueous sodium chloride solution
  5. dry with materialdried (sodium sulphate)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified by normal phase chromatography (mobile phase: cyclohexane/ethyl acetate 10-50% mixtures)

출처 및 근거

ORD 기록
ord-76ad4a5f4f9c42a59fe45ea71da5a4f0
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09434690B2

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