Potassium Phosphate, Tribasic → 6-(2-Chloro-pyrimidin-4-yloxy)-benzo[d]isoxazole-3-carboxylic acid (3-trifluoromethyl-phenyl)-amide

HRID 556341Notes

Reaction equation

HRID 556341 reaction equation
[F:1][C:2]([F:23])([F:22])[C:3]1[CH:4]=[C:5]([NH:9][C:10]([C:12]2[C:16]3[CH:17]=[CH:18][C:19]([OH:21])=[CH:20][C:15]=3[O:14][N:13]=2)=[O:11])[CH:6]=[CH:7][CH:8]=1.[Cl:24][C:25]1[N:30]=[C:29](Cl)[CH:28]=[CH:27][N:26]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN1C(=O)CCC1.C(Cl)Cl.C(O)(=O)CC(CC(O)=O)(C(O)=O)O.O>[F:23][C:2]([F:1])([F:22])[C:3]1[CH:4]=[C:5]([NH:9][C:10]([C:12]2[C:16]3[CH:17]=[CH:18][C:19]([O:21][C:27]4[CH:28]=[CH:29][N:30]=[C:25]([Cl:24])[N:26]=4)=[CH:20][C:15]=3[O:14][N:13]=2)=[O:11])[CH:6]=[CH:7][CH:8]=1

Participants

8

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 775312,4-DichloropyrimidineHCID 1363466276-Hydroxy-benzo[d]isoxazole-3-carboxylic acid (3-trifluoromethyl-phenyl)-amide

Product 1

HCID 247626256-(2-Chloro-pyrimidin-4-yloxy)-benzo[d]isoxazole-3-carboxylic acid (3-trifluoromethyl-phenyl)-amide

Reagents, catalysts & solvents 4

HCID 311Citric AcidSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A mixture of 294 mg (0.91 mMol) 6-hydroxy-benzo[d]isoxazole-3-carboxylic acid (3-trifluoromethyl-phenyl)-amide (Step 1.3), 149 mg (1.00 mMol) 2,4-dichlorpyrimidine and 426 mg (2.0 mMol) K3PO4 in 5 ml NMP is stirred for 20 h at rt. The reaction mixture is diluted with CH2Cl2 and 5% citric acid in water, the aq. phase separated off and extracted with CH2Cl2. The organic layers are washed with water and brine, dried (Na2SO4) and concentrated. Column chromatography (SiO2; CH2Cl2→CH2Cl2/EtOAc 99:1) gives the title compound: MS: [M+1]+=435; TLC(CH2Cl2/EtOAc 49:1): Rf=0.66.

Workup

  1. customthe aq. phase separated off
  2. extractionextracted with CH2Cl2
  3. washThe organic layers are washed with water and brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-8af72a9197c04a41821a478d46845114
Source dataset
uspto-grants-2011_11
Patent number
US08058276B2

Reaction notes

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