Phosphorus oxychloride → HCID 70663254, compound

HRID 878322Notes

Reaction equation

HRID 878322 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([O:9][CH3:10])=[CH:4][C:3]=1[C:11]1[CH:16]=[CH:15][N:14]=[CH:13][C:12]=1[NH:17][CH3:18].[CH3:19][S:20]([C:23]1[CH:24]=[C:25]([CH:29]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:31]=1)[C:26]([OH:28])=O)(=[O:22])=[O:21].O=P(Cl)(Cl)Cl>N1C=CC=CC=1>[F:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([O:9][CH3:10])=[CH:4][C:3]=1[C:11]1[CH:16]=[CH:15][N:14]=[CH:13][C:12]=1[N:17]([CH3:18])[C:26](=[O:28])[C:25]1[CH:29]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:31]=[C:23]([S:20]([CH3:19])(=[O:21])=[O:22])[CH:24]=1

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 215445163-Methanesulfonyl-5-(trifluoromethyl)benzoic acidHCID 70663306HCID 70663306, compound

Product 1

HCID 70663254HCID 70663254, compoundYield 29%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of [4-(2,4-difluoro-5-methoxy-phenyl)-pyridin-3-yl]-methyl-amine (70 mg, 0.28 mmol) in 2.5 mL pyridine were added 3-(methylsulfonyl)-5-(trifluoromethyl)benzoic acid (example 114, intermediate a) (90 mg, 0.34 mmol) and POCl3 (2.3 mL) dropwise at 25° C. and the reaction mixture was stirred for 12 hours at 25° C. The solvent was evaporated, the residue was dissolved in EtOAc (15 ml) and washed with 2M aqueous HCl solution (5 mL) followed by saturated NaHCO3 solution (10 mL). The organic layer was dried over anhydrous Na2SO4 and evaporated. The crude product was purified by preparative HPLC (ammonium acetate/acetonitrile) to furnish the title compound as a light yellow solid (40 mg, 29%). MS (ESI): m/z=501.2 [M+H]+.

Workup

  1. customThe solvent was evaporated
  2. dissolutionthe residue was dissolved in EtOAc (15 ml)
  3. washwashed with 2M aqueous HCl solution (5 mL)
  4. dry with materialThe organic layer was dried over anhydrous Na2SO4
  5. customevaporated
  6. customThe crude product was purified by preparative HPLC (ammonium acetate/acetonitrile)

Sources & evidence

ORD record
ord-1337d4b75e7c4b27a64095fd8e5741ed
Source dataset
uspto-grants-2015_03
Patent number
US08987307B2

Reaction notes

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