Hydrochloric Acid → HCID 69207886, compound

HRID 30720Notes

Reaction equation

HRID 30720 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH3:13])[N:11]=[CH:10][C:9]=2/[CH:14]=[CH:15]/[C:16]([NH:18][C:19]2[CH:33]=[CH:32][C:22]([CH2:23][NH:24][C:25](=[O:31])OC(C)(C)C)=[CH:21][CH:20]=2)=[O:17])=[CH:4][CH:3]=1.Cl.[C:35](OCC)(=O)[CH3:36]>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH3:13])[N:11]=[CH:10][C:9]=2/[CH:14]=[CH:15]/[C:16]([NH:18][C:19]2[CH:33]=[CH:32][C:22]([CH2:23][NH:24][C:25](=[O:31])[CH2:35][CH3:36])=[CH:21][CH:20]=2)=[O:17])=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 86602528tert-butyl [4-({(2E)-3-[5-(4-fluorophenyl)-1-methyl-1H-pyrazol-4-yl]prop-2-enoyl}amino)benzyl]carbamate

Product 1

HCID 69207886HCID 69207886, compound

Conditions

Temperature
70 °C

Procedure

A mixture of tert-butyl [4-({(2E)-3-[5-(4-fluorophenyl)-1-methyl-1H-pyrazol-4-yl]prop-2-enoyl}amino)benzyl]carbamate (2.0 g) and 4N hydrogenchloride in ethyl acetate (80 mL) was stirred at 70° C. for 15 hrs. The precipitated crystals were collected by filtration, and washed with ethyl acetate. Triethylamine (0.39 g) was added to a solution (10 mL) of the obtained crystals (1.00 g) in N,N-dimethylacetamide at room temperature. The reaction mixture was stirred at room temperature for 30 min. and propionyl chloride (0.27 g) was added. The reaction mixture was further stirred at room temperature for 2.5 days. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate-tetrahydrofuran. The organic layer was washed successively with 1N hydrochloric acid, saturated aqueous sodium hydrogen carbonate and saturated brine, dried over anhydrous magnesium sulfate, and concentrated to give (2E)-3-[5-(4-fluorophenyl)-1-methyl-1H-pyrazol-4-yl]-N-{4-[(propionylamino)methyl]phenyl}acrylamide as colorless crystals (0.51 g). Recrystallization thereof from acetone-hexane gave colorless prism crystals. melting point: 271-272° C.

Workup

  1. filtrationThe precipitated crystals were collected by filtration
  2. washwashed with ethyl acetate
  3. additionTriethylamine (0.39 g) was added to a solution (10 mL) of the obtained crystals (1.00 g) in N,N-dimethylacetamide at room temperature
  4. stirringThe reaction mixture was stirred at room temperature for 30 min.
  5. additionpropionyl chloride (0.27 g) was added
  6. stirringThe reaction mixture was further stirred at room temperature for 2.5 days
  7. additionWater was poured into the reaction mixture
  8. extractionthe mixture was extracted with ethyl acetate-tetrahydrofuran
  9. washThe organic layer was washed successively with 1N hydrochloric acid, saturated aqueous sodium hydrogen carbonate and saturated brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-1d0f83c637754202888afd94992b5120
Source dataset
uspto-grants-2008_09
Patent number
US07423159B2

Reaction notes

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