Ethyl Acetate → n-[2-[1-(3-Chloro-2-pyridinyl)-3-(trifluoromethyl)-1h-pyrazol-5-yl]-8-methyl-4h-3,1-benzoxazin-4-ylidene]-2-propanamine

HRID 857852Notes

Reaction equation

HRID 857852 reaction equation
[Cl:1][C:2]1[C:3]([N:8]2[C:12]([C:13]([NH:15][C:16]3[C:21]([C:22]([NH:24][CH:25]([CH3:27])[CH3:26])=[O:23])=[CH:20][CH:19]=[CH:18][C:17]=3[CH3:28])=O)=[CH:11][C:10]([C:29]([F:32])([F:31])[F:30])=[N:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1.C(OCC)(=O)C>P(Cl)(Cl)(Cl)=O>[Cl:1][C:2]1[C:3]([N:8]2[C:12]([C:13]3[O:23][C:22](=[N:24][CH:25]([CH3:27])[CH3:26])[C:21]4[CH:20]=[CH:19][CH:18]=[C:17]([CH3:28])[C:16]=4[N:15]=3)=[CH:11][C:10]([C:29]([F:30])([F:31])[F:32])=[N:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 8857Ethyl AcetateHCID 102985871-(3-chloro-2-pyridinyl)-N-[2-methyl-6-[[(1-methylethyl)amino]carbonyl]phenyl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide

Product 1

HCID 10225699n-[2-[1-(3-Chloro-2-pyridinyl)-3-(trifluoromethyl)-1h-pyrazol-5-yl]-8-methyl-4h-3,1-benzoxazin-4-ylidene]-2-propanamineYield 38.6%

Reagents, catalysts & solvents 1

HCID 24813Phosphorus oxychlorideSolvent

Procedure

A stirred solution of the title compound from Step D (1.2 g, 2.6 mmol) in 8 mL of phosphorous oxychloride was heated at reflux for 8 hours. The hot reaction solution was poured onto a large excess of ice and 100 ml of ethyl acetate added almost immediately (before allowing all of the ice to melt). After stirring and allowing the remaining ice to melt, the ethyl acetate layer was separated, washed with water, aqueous saturated sodium bicarbonate and brine. Followed by drying over magnesium sulfate, the solvent was removed in vacuo to give a crude yellow oily solid residue. Purification by flash chromatography on silica gel (4:1 hexane/ethyl acetate as eluant) afforded 450 mg of the title compound, a compound of the invention, isolated as a white solid melting at 175–176° C.

Workup

  1. temperatureat reflux for 8 hours
  2. additionadded almost immediately (
  3. customthe ethyl acetate layer was separated
  4. washwashed with water, aqueous saturated sodium bicarbonate and brine
  5. dry with materialFollowed by drying over magnesium sulfate
  6. customthe solvent was removed in vacuo
  7. customto give a crude yellow oily solid residue
  8. customPurification by flash chromatography on silica gel (4:1 hexane/ethyl acetate as eluant)

Sources & evidence

ORD record
ord-e9da73c7500c4e01954614202bb2d8c0
Source dataset
uspto-grants-2006_12
Patent number
US07148217B2

Reaction notes

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