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

HRID 56932

Reaction equation

HRID 56932 reaction equation
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

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

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)

Workup

  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)

Sources & evidence

ORD record
ord-76ad4a5f4f9c42a59fe45ea71da5a4f0
Source dataset
uspto-grants-2016_09
Patent number
US09434690B2

Linked notes

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