Benzenesulfonic Acid → 4{4-[3-(4-Chloro-3-trifluoromethylphenyl)-ureido]-3-fluorophenoxy}-pyridine-2-carboxylic acid methylamide phenylsulfonate

HRID 475443Notes

Reaction equation

HRID 475443 reaction equation
[CH3:1][NH:2][C:3]([C:5]1[CH:10]=[C:9]([O:11][C:12]2[CH:17]=[CH:16][C:15]([NH:18][C:19]([NH:21][C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[C:24]([C:29]([F:32])([F:31])[F:30])[CH:23]=3)=[O:20])=[C:14]([F:33])[CH:13]=2)[CH:8]=[CH:7][N:6]=1)=[O:4].[C:34]1([S:40]([OH:43])(=[O:42])=[O:41])[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1>C(O)C>[C:34]1([S:40]([OH:43])(=[O:42])=[O:41])[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.[CH3:1][NH:2][C:3]([C:5]1[CH:10]=[C:9]([O:11][C:12]2[CH:17]=[CH:16][C:15]([NH:18][C:19]([NH:21][C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[C:24]([C:29]([F:32])([F:31])[F:30])[CH:23]=3)=[O:20])=[C:14]([F:33])[CH:13]=2)[CH:8]=[CH:7][N:6]=1)=[O:4]

Participants

4

Reactant 2

HCID 7371Benzenesulfonic AcidHCID 11167602Regorafenib

Product 1

HCID 874054824{4-[3-(4-Chloro-3-trifluoromethylphenyl)-ureido]-3-fluorophenoxy}-pyridine-2-carboxylic acid methylamide phenylsulfonateYield 69%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

The compound of example 1 as a free base (2.25 g) was suspended in ethanol (50 mL) and benzensulfonic acid (0.737 g) in ethanol (50 mL) was added. The mixture was heated with vigorous stirring. All solid material dissolved to give a reddish solution. The solution was allowed to cool to room temperature and the flask scratched. Crystal formation was difficult to achieve, some seeds were found, added to solution and placed in freezer overnight. Grayish-tan solids had formed in the flask; the material was broken up & collected by suction filtration. The solids were washed with ethanol, then hexane and air-dried. Weighed product: 2.05 g, 69% yield.

Workup

  1. temperatureThe mixture was heated with vigorous stirring
  2. dissolutionAll solid material dissolved
  3. customto give a reddish solution
  4. additionadded to solution
  5. customhad formed in the flask
  6. filtrationcollected by suction filtration
  7. washThe solids were washed with ethanol
  8. dry with materialhexane and air-dried

Sources & evidence

ORD record
ord-e81adf21d6f54daa937e6ac553879038
Source dataset
uspto-grants-2014_01
Patent number
US08637553B2

Reaction notes

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