Diisopropylethylamine → tert-Butyl 4-{[2-{4-[5-chloro-2-(trifluoromethyl)phenyl]-2-oxopyridin-1(2H)-yl}-3-(pyridin-2-yl)propanoyl]amino}benzoate

HRID 56676

Reaction equation

HRID 56676 reaction equation
C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.C(N(CC)C(C)C)(C)C.[Cl:28][C:29]1[CH:30]=[CH:31][C:32]([C:53]([F:56])([F:55])[F:54])=[C:33]([C:35]2[CH:40]=[CH:39][N:38]([CH:41]([CH2:45][C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][N:47]=3)[C:42](O)=[O:43])[C:37](=[O:52])[CH:36]=2)[CH:34]=1.[NH2:57][C:58]1[CH:70]=[CH:69][C:61]([C:62]([O:64][C:65]([CH3:68])([CH3:67])[CH3:66])=[O:63])=[CH:60][CH:59]=1>C(OCC)(=O)C.O.C(OCC)(=O)C>[Cl:28][C:29]1[CH:30]=[CH:31][C:32]([C:53]([F:56])([F:54])[F:55])=[C:33]([C:35]2[CH:40]=[CH:39][N:38]([CH:41]([CH2:45][C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][N:47]=3)[C:42]([NH:57][C:58]3[CH:70]=[CH:69][C:61]([C:62]([O:64][C:65]([CH3:66])([CH3:67])[CH3:68])=[O:63])=[CH:60][CH:59]=3)=[O:43])[C:37](=[O:52])[CH:36]=2)[CH:34]=1

Participants

7

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 111923Propylphosphonic anhydride2×HCID 233272Benzoic acid, 4-amino-, 1,1-dimethylethyl esterHCID 1176228292-{4-[5-Chloro-2-(trifluoromethyl)phenyl]-2-oxopyridin-1(2H)-yl}-3-(pyridin-2-yl)propanoic acid

Product 1

HCID 117622565tert-Butyl 4-{[2-{4-[5-chloro-2-(trifluoromethyl)phenyl]-2-oxopyridin-1(2H)-yl}-3-(pyridin-2-yl)propanoyl]amino}benzoate

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 22728543Water ethylacetateSolvent

Conditions

Temperature
60 °C

Procedure

Under argon and at 0° C., 707 mg (50% strength in ethyl acetate, 1.11 mmol) of T3P and 0.29 ml (1.67 mmol) of N,N-diisopropylethylamine were added to a solution of 470 mg (purity 50%, 0.56 mmol) of 2-{4-[5-chloro-2-(trifluoromethyl)phenyl]-2-oxopyridin-1(2H)-yl}-3-(pyridin-2-yl)propanoic acid (racemate) and 129 mg (0.67 mmol) of tert-butyl 4-aminobenzoate in 45 ml of ethyl acetate. The reaction mixture was stirred at 60° C. for 1 h, another 353 mg (50% strength in ethyl acetate, 0.56 mmol) of T3P and 0.1 ml (0.56 mmol) of N,N-diisopropylethylamine were added and the mixture was stirred at 60° C. for 1 h. After addition of water/ethyl acetate and phase separation, the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried (sodium sulphate), filtered and concentrated under reduced pressure. The crude product was purified by flash chromatography (silica gel 60, dichloromethane/methanol mixtures). Yield: 163 mg (purity 93%, 46% of theory)

Workup

  1. stirringthe mixture was stirred at 60° C. for 1 h
  2. extractionthe aqueous phase was extracted three times with ethyl acetate
  3. dry with materialThe combined organic phases were dried (sodium sulphate)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified by flash chromatography (silica gel 60, dichloromethane/methanol mixtures)

Sources & evidence

ORD record
ord-95c19b25e17446a69aba8eb1b47ef77b
Source dataset
uspto-grants-2016_09
Patent number
US09434690B2

Linked notes

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