Ethanol → Edoxaban tosylate monohydrate

HRID 1952000Notes

Reaction equation

HRID 1952000 reaction equation
[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([OH:11])(=[O:10])=[O:9])=[CH:6][CH:7]=1.O.[Cl:13][C:14]1[CH:15]=[CH:16][C:17]([NH:20][C:21](=[O:49])[C:22]([NH:24][C@H:25]2[CH2:30][CH2:29][C@H:28]([C:31]([N:33]([CH3:35])[CH3:34])=[O:32])[CH2:27][C@H:26]2[NH:36][C:37]([C:39]2[S:40][C:41]3[CH2:42][N:43]([CH3:48])[CH2:44][CH2:45][C:46]=3[N:47]=2)=[O:38])=[O:23])=[N:18][CH:19]=1.C(O)C>O>[OH2:9].[C:2]1([CH3:1])[CH:3]=[CH:4][C:5]([S:8]([OH:11])(=[O:9])=[O:10])=[CH:6][CH:7]=1.[Cl:13][C:14]1[CH:15]=[CH:16][C:17]([NH:20][C:21](=[O:49])[C:22]([NH:24][C@H:25]2[CH2:30][CH2:29][C@H:28]([C:31]([N:33]([CH3:35])[CH3:34])=[O:32])[CH2:27][C@H:26]2[NH:36][C:37]([C:39]2[S:40][C:41]3[CH2:42][N:43]([CH3:48])[CH2:44][CH2:45][C:46]=3[N:47]=2)=[O:38])=[O:23])=[N:18][CH:19]=1

Participants

5

Reactant 3

HCID 702EthanolHCID 521998p-Toluenesulfonic acid monohydrateHCID 10280735Edoxaban

Product 1

HCID 25022378Edoxaban tosylate monohydrateYield 196.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

TsOH.H2O (49.5 g) was added to a mixed solution of N1-(5-chloropyridin-2-yl)-N2-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide (150 g), ethanol (735 ml), and water (315 ml), and the mixture was heated to 70° C. The dissolved solution was filtered through a filter, and the filter was washed with 15% aqueous ethanol (300 ml) and ethanol (150 ml). Subsequently, a mixed solution of the filtered mother liquor and the washes was slowly cooled, and TsOH.H2O (7.8 g) and ethanol (2100 ml) were added thereto. After stirring at 10° C. for 1 hour, crystals were collected by filtration, to obtain 188.9 g of the title compound.

Workup

  1. filtrationThe dissolved solution was filtered through a filter
  2. washthe filter was washed with 15% aqueous ethanol (300 ml) and ethanol (150 ml)
  3. temperatureSubsequently, a mixed solution of the filtered mother liquor and the washes was slowly cooled
  4. additionTsOH.H2O (7.8 g) and ethanol (2100 ml) were added
  5. filtrationcrystals were collected by filtration

Sources & evidence

ORD record
ord-b73af209a8cb40eebf08d87aad55597f
Source dataset
uspto-grants-2013_03
Patent number
US08404847B2

Reaction notes

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