Acetone → Ticagrelor Fumarate

HRID 589827Notes

Reaction equation

HRID 589827 reaction equation
[CH3:1][CH2:2][CH2:3][S:4][C:5]1[N:6]=[C:7]([NH:25][C@H:26]2[C@H:28]([C:29]3[CH:30]=[CH:31][C:32]([F:36])=[C:33]([F:35])[CH:34]=3)[CH2:27]2)[C:8]2[N:13]=[N:12][N:11]([C@H:14]3[C@H:18]([OH:19])[C@H:17]([OH:20])[C@@H:16]([O:21][CH2:22][CH2:23][OH:24])[CH2:15]3)[C:9]=2[N:10]=1.CC(C)=O.[C:41]([OH:48])(=[O:47])/[CH:42]=[CH:43]/[C:44]([OH:46])=[O:45]>CCCCCC>[CH3:1][CH2:2][CH2:3][S:4][C:5]1[N:6]=[C:7]([NH:25][C@H:26]2[C@H:28]([C:29]3[CH:30]=[CH:31][C:32]([F:36])=[C:33]([F:35])[CH:34]=3)[CH2:27]2)[C:8]2[N:13]=[N:12][N:11]([C@H:14]3[C@H:18]([OH:19])[C@H:17]([OH:20])[C@@H:16]([O:21][CH2:22][CH2:23][OH:24])[CH2:15]3)[C:9]=2[N:10]=1.[C:41]([O-:48])(=[O:47])/[CH:42]=[CH:43]/[C:44]([O-:46])=[O:45]

Participants

5

Reactant 3

HCID 180AcetoneHCID 444972Fumaric AcidHCID 9871419Ticagrelor

Product 1

HCID 131734468Ticagrelor FumarateYield 65%

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent

Conditions

Temperature
27.5 °C

Procedure

Ticagrelor (0.5 g) and acetone (13 mL) were charged into a round bottom flask and the mixture was stirred at about 25-30° C. for about 15 minutes for clear solution. Then fumaric acid (0.12 g) was added to the above reaction mixture at 25-35° C. and mixture was stirred for 4-5 hours. To the clear solution, n-hexane (50 mL) was added and stirred for about 90 minutes for solid separation. The solid was filtered, washed with n-hexane (5 mL) and dried to afford the title compound in about 65% yield having chiral HPLC purity of about 99.8%.

Workup

  1. stirringmixture was stirred for 4-5 hours
  2. stirringstirred for about 90 minutes for solid separation
  3. filtrationThe solid was filtered
  4. washwashed with n-hexane (5 mL)
  5. customdried

Sources & evidence

ORD record
ord-715f2790e1614615b27b01e19c3f1f45
Source dataset
uspto-grants-2016_01
Patent number
US09233966B2

Reaction notes

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