Methanesulfonic Acid → Regorafenib mesylate

HRID 475442Notes

Reaction equation

HRID 475442 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].[CH3:34][S:35]([OH:38])(=[O:37])=[O:36]>C(O)C>[S:35]([OH:38])(=[O:37])(=[O:36])[CH3:34].[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 6395Methanesulfonic AcidHCID 11167602Regorafenib

Product 1

HCID 87404842Regorafenib mesylate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

The compound of example 1 as a free base (2.25 g) was dissolved in ethanol (100 mL) and a stock solution of methanesulfonic acid (excess) was added. The solution was then concentrated in vacuo to afford a yellow oil. Ethanol was added and concentration repeated, affording 2.41 g of off-white solids. The crude salt was dissolved in hot ethanol (˜125 mL) and then cooled slowly to crystallize. After reaching room temperature, the flask was placed in a freezer overnight. The colorless crystalline material was collected by suction filtration; the filter cake was washed with ethanol, then hexane and air-dried, to afford 2.05 g of material, which was dried in a vacuum oven at 60° C. overnight.

Workup

  1. concentrationThe solution was then concentrated in vacuo
  2. customto afford a yellow oil
  3. concentrationconcentration

Sources & evidence

ORD record
ord-4bc40f14e8a74ce9a3da32fa2866a9eb
Source dataset
uspto-grants-2014_01
Patent number
US08637553B2

Reaction notes

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