HCID 59548010, compound → HCID 46945202, compound

HRID 1946430Notes

Reaction equation

HRID 1946430 reaction equation
[P:1]([O:39]CC1C=CC=CC=1)([O:31]CC1C=CC=CC=1)([O:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][N:11]2[CH:15]=[CH:14][C:13]([NH:16][C:17]([C:19]3[C:24]([F:25])=[CH:23][CH:22]=[CH:21][C:20]=3[F:26])=[O:18])=[N:12]2)=[C:6]([C:27]([F:30])([F:29])[F:28])[CH:5]=1)=[O:2]>C(O)C.CO.CS(C)=O.[Pd]>[P:1]([OH:39])([OH:31])([O:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][N:11]2[CH:15]=[CH:14][C:13]([NH:16][C:17]([C:19]3[C:24]([F:25])=[CH:23][CH:22]=[CH:21][C:20]=3[F:26])=[O:18])=[N:12]2)=[C:6]([C:27]([F:30])([F:29])[F:28])[CH:5]=1)=[O:2]

Participants

5

Reactant 1

HCID 59548010HCID 59548010, compound

Product 1

HCID 46945202HCID 46945202, compound

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 22036561Dimethyl sulfoxide methanolSolvent

Procedure

A solution of 4-[(3-{[(2,6-difluorophenyl)carbonyl]amino}-1H-pyrazol-1-yl)methyl]-3-(trifluoromethyl)phenyl bis(phenylmethyl) phosphate (for a preparation see Intermediate 58)(15.85 g, 24.1 mmol) in ethanol (200 ml) was hydrogenated using the H-cube midi (settings: 25° C., 15 bar, 10 ml/min flow rate) and 10% Pd/C CatCart as the catalyst. The solvent was evaporated in vacuo to give a white foam. The sample was loaded in methanol/DMSO and purified on reverse phase (C18) 1900 g using a 0-50% acetonitrile (+0.1% TFA)-water(+0.1% TFA) over 7 column volumes. The appropriate fractions were combined and the acetonitrile was removed in vacuo. The resulting suspension was filtered to give 4-[(3-{[(2,6-difluorophenyl)carbonyl]amino}-1H-pyrazol-1-yl)methyl]-3-(trifluoromethyl)phenyl dihydrogen phosphate (5.02 g). The filtrate was extracted using ethyl acetate (600 ml). The organic phase was dried over magnesium sulphate and evaporated in vacuo to give a further amount of 4-[(3-{[(2,6-difluorophenyl)carbonyl]amino}-1H-pyrazol-1-yl)methyl]-3-(trifluoromethyl)phenyl dihydrogen phosphate as a white solid (2.39 g).

Workup

  1. customThe solvent was evaporated in vacuo
  2. customto give a white foam
  3. custompurified on reverse phase (C18) 1900 g
  4. customthe acetonitrile was removed in vacuo
  5. filtrationThe resulting suspension was filtered

Sources & evidence

ORD record
ord-bdef8a77de6b40378fd88221c7cac254
Source dataset
uspto-grants-2013_03
Patent number
US08399436B2

Reaction notes

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