p-Toluenesulfonic acid → Edoxaban tosylate monohydrate

HRID 707490Notes

Reaction equation

HRID 707490 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9](=[O:37])[C:10]([NH:12][C@H:13]2[CH2:18][CH2:17][C@H:16]([C:19]([N:21]([CH3:23])[CH3:22])=[O:20])[CH2:15][C@H:14]2[NH:24][C:25]([C:27]2[S:28][C:29]3[CH2:30][N:31]([CH3:36])[CH2:32][CH2:33][C:34]=3[N:35]=2)=[O:26])=[O:11])=[N:6][CH:7]=1.[C:38]1([CH3:48])[CH:43]=[CH:42][C:41]([S:44]([OH:47])(=[O:46])=[O:45])=[CH:40][CH:39]=1>C(Cl)Cl.C(O)C>[OH2:11].[C:38]1([CH3:48])[CH:39]=[CH:40][C:41]([S:44]([OH:47])(=[O:45])=[O:46])=[CH:42][CH:43]=1.[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9](=[O:37])[C:10]([NH:12][C@H:13]2[CH2:18][CH2:17][C@H:16]([C:19]([N:21]([CH3:23])[CH3:22])=[O:20])[CH2:15][C@H:14]2[NH:24][C:25]([C:27]2[S:28][C:29]3[CH2:30][N:31]([CH3:36])[CH2:32][CH2:33][C:34]=3[N:35]=2)=[O:26])=[O:11])=[N:6][CH:7]=1

Participants

5

Reactant 2

HCID 6101p-Toluenesulfonic acidHCID 10280735Edoxaban

Product 1

HCID 25022378Edoxaban tosylate monohydrate

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

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 (A) (6.2 g) was dissolved in methylene chloride (120 ml). To the solution, a 1 mol/L solution of p-toluenesulfonic acid in ethanol (11.28 ml) was added, and the solvent was distilled off. To the residue, 15% hydrous ethanol (95 ml) was added, and the mixture was dissolved by stirring at 60° C. Then, the mixture was cooled to room temperature and stirred for 1 day. The precipitated crystals were collected by filtration, washed with ethanol, and then dried under reduced pressure at room temperature for 2 hours to obtain the title compound (A-a) (7.4 g).

Workup

  1. distillationthe solvent was distilled off
  2. additionTo the residue, 15% hydrous ethanol (95 ml) was added
  3. dissolutionthe mixture was dissolved
  4. temperatureThen, the mixture was cooled to room temperature
  5. stirringstirred for 1 day
  6. filtrationThe precipitated crystals were collected by filtration
  7. washwashed with ethanol
  8. customdried under reduced pressure at room temperature for 2 hours

Sources & evidence

ORD record
ord-75afaa6ac4be46cfb59374035f720c76
Source dataset
uspto-grants-2015_11
Patent number
US09175012B2

Reaction notes

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