Potassium Phosphate, Tribasic → 6-(2-Amino-6-chloro-pyrimidin-4-yloxy)-benzo[d]isothiazole-3-carboxylic acid (4-fluoro-3-trifluoromethyl-phenyl)-amide

HRID 556356Notes

Reaction equation

HRID 556356 reaction equation
[NH2:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[C:4]([Cl:9])[N:3]=1.[F:10][C:11]1[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]2[C:24]3[CH:25]=[CH:26][C:27]([OH:29])=[CH:28][C:23]=3[S:22][N:21]=2)=[O:19])=[CH:13][C:12]=1[C:30]([F:33])([F:32])[F:31].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN1C(=O)CCC1.CCOC(C)=O.O>[F:10][C:11]1[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]2[C:24]3[CH:25]=[CH:26][C:27]([O:29][C:6]4[CH:5]=[C:4]([Cl:9])[N:3]=[C:2]([NH2:1])[N:7]=4)=[CH:28][C:23]=3[S:22][N:21]=2)=[O:19])=[CH:13][C:12]=1[C:30]([F:32])([F:31])[F:33]

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 655222-Amino-4,6-dichloropyrimidineHCID 1363466286-Hydroxy-benzo[d]isothiazole-3-carboxylic acid (4-fluoro-3-trifluoromethyl-phenyl)-amide

Product 1

HCID 866266256-(2-Amino-6-chloro-pyrimidin-4-yloxy)-benzo[d]isothiazole-3-carboxylic acid (4-fluoro-3-trifluoromethyl-phenyl)-amide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 72 mg (0.44 mMol) 2-amino-4,6-dichloropyrimidine, 143 mg (0.40 mMol) 6-hydroxy-benzo[d]isothiazole-3-carboxylic acid (4-fluoro-3-trifluoromethyl-phenyl)-amide and 280 mg (1.32 mMol) K3PO4 in 2 ml NMP is stirred for 6 h at 70° C. Then the mixture is diluted with EtOAc and water, the aq. layer separated off and extracted twice with EtOAc. The organic phases are washed twice with water and brine, dried (Na2SO4) and concentrated. Chromatography (Combi Flash; CH2Cl2→CH2Cl2/EtOH 9:1) gives the title compound: MS: [M−1]=482/484; TLC(CH2Cl2): Rf=0.12.

Workup

  1. customthe aq. layer separated off
  2. extractionextracted twice with EtOAc
  3. washThe organic phases are washed twice with water and brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-56155e3f1f6f49d6ba2a3284afad336f
Source dataset
uspto-grants-2011_11
Patent number
US08058276B2

Reaction notes

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