Piconol → HCID 11351086, compound

HRID 403030Notes

Reaction equation

HRID 403030 reaction equation
[CH:1]1([NH:4][C:5]([C:7]2[CH:8]=[CH:9][C:10]([CH3:25])=[C:11]([NH:13][C:14](=[O:24])[C:15]3[CH:20]=[C:19]([F:21])[C:18](F)=[C:17]([F:23])[CH:16]=3)[CH:12]=2)=[O:6])[CH2:3][CH2:2]1.[N:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[CH2:32][OH:33].CC(C)([O-])C.[K+]>CN1C(=O)CCC1.C(OCC)(=O)C>[CH:1]1([NH:4][C:5]([C:7]2[CH:8]=[CH:9][C:10]([CH3:25])=[C:11]([NH:13][C:14](=[O:24])[C:15]3[CH:20]=[C:19]([F:21])[C:18]([O:33][CH2:32][C:27]4[CH:28]=[CH:29][CH:30]=[CH:31][N:26]=4)=[C:17]([F:23])[CH:16]=3)[CH:12]=2)=[O:6])[CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 11474PiconolHCID 23665647Potassium tert-butoxideHCID 66631543HCID 66631543, compound

Product 1

HCID 11351086HCID 11351086, compoundYield 23%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
180 °C

Procedure

A mixture of N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-3,4,5-trifluorobenzamide (100 mg, 0.29 mmol), 2-pyridinylmethanol (400 μl) and potassium t-butoxide (32 mg, 0.29 mmol) in NMP (600 μl) was heated in the microwave at 180° C. for 1.5 hrs. The reaction mixture was cooled and partitioned between saturated aqueous sodium bicarbonate and ethyl acetate. The organic phase was washed with dilute aqueous citric acid. Evaporation of the ethyl acetate gave impure product which was purified on silica column chromatography eluting with 0 to 100% ethyl acetate in isohexane. The solvents were evaporated to give a residue which was dissolved in ethyl acetate, then extracted with dilute hydrochloric acid. The aqueous extracts were basified with saturated aqueous sodium bicarbonate solution and then extracted with ethyl acetate to give the title compound as a solid (29 mg, 23%); NMR Spectrum: (DMSOd6) 0.58 (m, 2H), 0.69 (m, 2H), 2.25 (s, 3H), 2.85 (m, 1H), 5.36 (s, 2H), 7.37 (m, 2H), 7.64 (m, 2H), 7.84 (m, 4H), 8.40 (m, 1H), 8.56 (m, 1H), 10.14 (s, 1H); Mass Spectrum: M−H− 436.

Workup

  1. temperatureThe reaction mixture was cooled
  2. custompartitioned between saturated aqueous sodium bicarbonate and ethyl acetate
  3. washThe organic phase was washed with dilute aqueous citric acid
  4. customEvaporation of the ethyl acetate
  5. customgave impure product which
  6. customwas purified on silica column chromatography
  7. washeluting with 0 to 100% ethyl acetate in isohexane
  8. customThe solvents were evaporated
  9. customto give a residue which
  10. extractionextracted with dilute hydrochloric acid
  11. extractionextracted with ethyl acetate

Sources & evidence

ORD record
ord-999413d9889e4cd6b582e1f7af283fbc
Source dataset
uspto-grants-2014_06
Patent number
US08742124B2

Reaction notes

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