Potassium Phosphate, Tribasic → HCID 46944993, compound

HRID 1946413Notes

Reaction equation

HRID 1946413 reaction equation
I[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]2[CH:13]=[CH:12][C:11]([NH:14][C:15](=[O:23])[C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[Cl:22])=[N:10]2)=[C:4]([C:24]([F:27])([F:26])[F:25])[CH:3]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(P([CH:49]2[CH2:54][CH2:53]CCC2)C2CCCCC2)CCCCC1.C1(B(O)O)CC1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[Cl:22][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1[C:15]([NH:14][C:11]1[CH:12]=[CH:13][N:9]([CH2:8][C:5]2[CH:6]=[CH:7][C:2]([CH:53]3[CH2:54][CH2:49]3)=[CH:3][C:4]=2[C:24]([F:27])([F:26])[F:25])[N:10]=1)=[O:23]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 59547940HCID 59547940, compound

Product 1

HCID 46944993HCID 46944993, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of N-(1-{[4-iodo-2-(trifluoromethyl)phenyl]methyl}-1H-pyrazol-3-yl)-2-chlorobenzamide (for a preparation see Example 95)(30 mg, 0.059 mmol) was added potassium phosphate tribasic (38 mg, 0.179 mmol, Aldrich), tricyclohexyl phosphine (5 mg, 0.018 mmol, Aldrich), cyclopropyl boronic acid (16 mg, 0.186 mmol, Fluorochem) in toluene (2 ml). Water (0.1 ml) was added followed by palladium (II) acetate (4 mg, 0.018 mmol, ABCR). The resulting yellow suspension was heated to 100° C. and stirred under nitrogen overnight. The reaction mixture was partitioned between DCM (10 ml) and water (10 ml). The phases were separated using a hydrophobic frit and the aqueous layer was washed with DCM (10 ml). The organic layers were combined and the solvent removed in vacuo. The residue was dissolved in 1:1 MeOH:DMSO (1 ml) and purified by MDAP on Sunfire C18 column (Method B) using Acetonitrile-Water with a Formic acid modifier. The solvent was evaporated in vacuo to give the title compound as a yellow gum (6 mg); LCMS: (System 4) MH+=420, tRET=3.22 min.

Workup

  1. customThe reaction mixture was partitioned between DCM (10 ml) and water (10 ml)
  2. customThe phases were separated
  3. washthe aqueous layer was washed with DCM (10 ml)
  4. customthe solvent removed in vacuo
  5. dissolutionThe residue was dissolved in 1:1 MeOH
  6. customDMSO (1 ml) and purified by MDAP on Sunfire C18 column (Method B)
  7. customThe solvent was evaporated in vacuo

Sources & evidence

ORD record
ord-72509ce717ea479cb7be16be5c4215cb
Source dataset
uspto-grants-2013_03
Patent number
US08399436B2

Reaction notes

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