p-Toluenesulfonic acid monohydrate → Edoxaban tosylate monohydrate

HRID 2361003Notes

Reaction equation

HRID 2361003 reaction equation
C1(C)C=CC(S(O)(=O)=[O:8])=CC=1.[Cl:12][C:13]1[CH:14]=[CH:15][C:16]([NH:19][C:20](=[O:48])[C:21]([NH:23][C@H:24]2[CH2:29][CH2:28][C@H:27]([C:30](=[O:34])[N:31]([CH3:33])[CH3:32])[CH2:26][C@H:25]2[NH:35][C:36]([C:38]2[S:39][C:40]3[CH2:41][N:42]([CH3:47])[CH2:43][CH2:44][C:45]=3[N:46]=2)=[O:37])=[O:22])=[N:17][CH:18]=1.O.[C:50]1([CH3:60])[CH:55]=[CH:54][C:53]([S:56]([OH:59])(=[O:58])=[O:57])=[CH:52][CH:51]=1>C(O)C>[OH2:8].[C:50]1([CH3:60])[CH:51]=[CH:52][C:53]([S:56]([OH:59])(=[O:57])=[O:58])=[CH:54][CH:55]=1.[Cl:12][C:13]1[CH:14]=[CH:15][C:16]([NH:19][C:20](=[O:48])[C:21]([NH:23][C@H:24]2[CH2:29][CH2:28][C@H:27]([C:30](=[O:34])[N:31]([CH3:33])[CH3:32])[CH2:26][C@H:25]2[NH:35][C:36]([C:38]2[S:39][C:40]3[CH2:41][N:42]([CH3:47])[CH2:43][CH2:44][C:45]=3[N:46]=2)=[O:37])=[O:22])=[N:17][CH:18]=1

Participants

4

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 44610678Edoxaban tosylate

Product 1

HCID 25022378Edoxaban tosylate monohydrate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent3×

Conditions

Temperature
70 °C

Procedure

N-(5-Chloropyridin-2-yl)-N′-[(1S,2R,4S)-4-(dimethylcarbamoyl)-2-{[(5-methyl-4,5,6,7-tetrahydro[1,3]thiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl]ethanediamide p-toluenesulfonic acid (86.8 g) was dissolved in 30% hydrous ethanol (418 mL) at 60° C., and a solution (167 mL) of p-toluenesulfonic acid monohydrate (29.0 g) in 30% hydrous ethanol was added to the solution. The mixture was stirred at 70° C. for 1 hour, and then gradually cooled. At room temperature, ethanol was added to the cooled mixture, followed by stirring for 16 hours. The reaction mixture was stirred under ice-cooling for 1 hour, and the formed crystals were recovered by filtration, to thereby yield 102.9 g of the title compound.

Workup

  1. temperaturegradually cooled
  2. stirringby stirring for 16 hours
  3. stirringThe reaction mixture was stirred under ice-
  4. temperaturecooling for 1 hour
  5. filtrationthe formed crystals were recovered by filtration

Sources & evidence

ORD record
ord-d9a98553f43c44b6b9b4c1f86ed21b2e
Source dataset
uspto-grants-2014_04
Patent number
US08686189B2

Reaction notes

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