HCID 86675133, compound → HCID 86675132, compound

HRID 587674Notes

Reaction equation

HRID 587674 reaction equation
[CH:1]1([C:4]([NH:6][NH:7][C:8](=O)[CH2:9][NH:10][C:11](=[O:34])[C:12]2[CH:17]=[CH:16][C:15](/[CH:18]=[CH:19]/[CH:20]([C:25]3[CH:30]=[C:29]([Cl:31])[CH:28]=[C:27]([Cl:32])[CH:26]=3)[C:21]([F:24])([F:23])[F:22])=[CH:14][C:13]=2[CH3:33])=[O:5])[CH2:3][CH2:2]1>P(Cl)(Cl)(Cl)=O>[CH:1]1([C:4]2[O:5][C:8]([CH2:9][NH:10][C:11](=[O:34])[C:12]3[CH:17]=[CH:16][C:15](/[CH:18]=[CH:19]/[CH:20]([C:25]4[CH:26]=[C:27]([Cl:32])[CH:28]=[C:29]([Cl:31])[CH:30]=4)[C:21]([F:22])([F:24])[F:23])=[CH:14][C:13]=3[CH3:33])=[N:7][N:6]=2)[CH2:2][CH2:3]1

Participants

3

Reactant 1

HCID 86675133HCID 86675133, compound

Product 1

HCID 86675132HCID 86675132, compound

Reagents, catalysts & solvents 1

HCID 24813Phosphorus oxychlorideSolvent

Conditions

Temperature
50 °C

Procedure

A solution of (E)-N-(2-(2-(cyclopropanecarbonyl)hydrazinyl)-2-oxoethyl)-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzamide (200 mg, 0.379 mmol) in phosphoryl chloride (POCl3, 2.0 mL) was stirred at ambient temperature for 10 min, then the resultant reaction mixture was heated to 50° C. for 1 h. The reaction mixture was quenched with ice water at 0° C. and extracted with EtOAc. The combined EtOAc layer was washed with saturated sodium bicarbonate (NaHCO3) solution and brine solution, dried over anhydrous Na2SO4, and concentrated under reduced pressure. Purification by flash column chromatography (SiO2, 100-200 mesh; eluting with 50% EtOAc/pet ether) afforded the title compound as a light brown gummy material (70.0 mg, 36%): 1H NMR (400 MHz, CDCl3) δ 7.43 (m, 2H), 7.27 (m, 2H), 7.23 (m, 2H), 6.58 (d, J=16.0 Hz, 1H), 6.41 (dd, J=16.0, 7.6 Hz, 1H), 4.79 (d, J=5.6 Hz, 2H), 4.14 (m, 1H), 2.48 (s, 3H), 2.18 (m, 1H), 1.16 (m, 4H); ESIMS m/z 509.89 ([M+H]+); IR (thin film) 1666, 1166, 1112, 800 cm−1.

Workup

  1. customthe resultant reaction mixture
  2. customThe reaction mixture was quenched with ice water at 0° C.
  3. extractionextracted with EtOAc
  4. washThe combined EtOAc layer was washed with saturated sodium bicarbonate (NaHCO3) solution and brine solution
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customPurification
  8. washby flash column chromatography (SiO2, 100-200 mesh; eluting with 50% EtOAc/pet ether)

Sources & evidence

ORD record
ord-26398723dff8422cae0b43b0d88e8b65
Source dataset
uspto-grants-2016_01
Patent number
US09226501B2

Reaction notes

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