Hydrochloric Acid → 4-cyano-7-fluoro-N,5-dimethyl-6-phenyl-N-propyl-1,3-benzoxazole-2-carboxamide

HRID 17572

Reaction equation

HRID 17572 reaction equation
C[Al](C)C.[CH3:5][NH:6][CH2:7][CH2:8][CH3:9].[C:10]([C:12]1[C:17]2[N:18]=[C:19]([C:21]([O:23]CC)=O)[O:20][C:16]=2[C:15]([F:26])=[C:14]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:13]=1[CH3:33])#[N:11].Cl>ClCCl.C1(C)C=CC=CC=1>[C:10]([C:12]1[C:17]2[N:18]=[C:19]([C:21]([N:6]([CH3:5])[CH2:7][CH2:8][CH3:9])=[O:23])[O:20][C:16]=2[C:15]([F:26])=[C:14]([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[C:13]=1[CH3:33])#[N:11]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 12315N-MethylpropylamineHCID 16682925TrimethylaluminumHCID 51041426Ethyl 4-cyano-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazole-2-carboxylate

Product 1

HCID 685854164-cyano-7-fluoro-N,5-dimethyl-6-phenyl-N-propyl-1,3-benzoxazole-2-carboxamideYield 55.4%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

Under nitrogen atmosphere, trimethylaluminium (1.03 M n-hexane solution) (2.40 ml, 2.47 mmol) was dropwise added at room temperature to a toluene (6 ml) solution of N-methylpropylamine (127 μl, 1.23 mmol), followed by stirring for 40 minutes. Subsequently, a dichloromethane (2 ml) solution of ethyl 4-cyano-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazole-2-carboxylate (I-111) (200 mg, 617 μmol) was dropwise added, followed by stirring for 48.5 hours. After the reaction, aqueous 1 N hydrochloric acid solution was added to the reaction liquid with cooling with ice, followed by stirring at room temperature, then the reaction liquid was extracted with chloroform. Next, the combined organic layer was dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by middle-pressure liquid chromatography (eluent, n-hexane:ethyl acetate=2:1, v/v) to obtain the entitled compound (120 mg, 55%) as a pale yellow solid.

Workup

  1. stirringby stirring for 48.5 hours
  2. additionwas added to the reaction liquid
  3. temperaturewith cooling with ice
  4. stirringby stirring at room temperature
  5. customthe reaction liquid
  6. extractionwas extracted with chloroform
  7. dry with materialNext, the combined organic layer was dried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationthe filtrate was concentrated under reduced pressure
  10. customThe resulting residue was purified by middle-pressure liquid chromatography (eluent, n-hexane

Sources & evidence

ORD record
ord-b3c9902835434202a8d24214e3949123
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Linked notes

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