Methanesulfonic Acid → Dabigatran Impurity p

HRID 1527152Notes

Reaction equation

HRID 1527152 reaction equation
[CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][O:7][C:8](/[N:10]=[C:11](\N)/[C:12]1[CH:13]=[CH:14][C:15]([NH:18][CH2:19][C:20]2[N:28]([CH3:29])[C:27]3[CH:26]=[CH:25][C:24]([C:30]([N:32]([C:40]4[CH:41]=[CH:42][CH:43]=[CH:44][N:45]=4)[CH2:33][CH2:34][C:35]([O:37]CC)=[O:36])=[O:31])=[CH:23][C:22]=3[N:21]=2)=[CH:16][CH:17]=1)=[O:9].CS(O)(=O)=[O:49].CS(O)(=O)=O>O>[CH2:6]([O:7][C:8]([NH:10][C:11]([C:12]1[CH:13]=[CH:14][C:15]([NH:18][CH2:19][C:20]2[N:28]([CH3:29])[C:27]3[CH:26]=[CH:25][C:24]([C:30]([N:32]([C:40]4[CH:41]=[CH:42][CH:43]=[CH:44][N:45]=4)[CH2:33][CH2:34][C:35]([OH:37])=[O:36])=[O:31])=[CH:23][C:22]=3[N:21]=2)=[CH:16][CH:17]=1)=[O:49])=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2][CH3:1]

Participants

4

Reactant 2

HCID 6395Methanesulfonic AcidHCID 11434065ethyl 3-[[2-[[4-[(Z)-N'-hexoxycarbonylcarbamimidoyl]anilino]methyl]-1-methylbenzimidazole-5-carbonyl]-pyridin-2-ylamino]propanoate;methanesulfonic acid

Product 1

HCID 70984799Dabigatran Impurity pYield 28.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
55 °C

Procedure

25 g of dabigatran etexilate mesylate were suspended in 180 mL of deionized water. 1.32 g of methanesulfonic acid were added. The reaction mixture was heated to 55° C. and stirred at this temperature for 7 days. The resulting mixture was filtered, and the solid was dried under vacuum. The solid was purified by column chromatography, eluting with dichloromethane:methanol (10:1 v/v) mixture. After solvent evaporation of the selected fractions containing the desired compound, 5.9 g of 3-{[(2-{[(4-{[({hexyloxy}carbonyl)amino]carbonyl}phenyl)-amino]methyl}-1-methyl-1H-benzimidazol-5-yl)carbonyl](pyridin-2-yl)amino}propanoic acid were obtained.

Workup

  1. filtrationThe resulting mixture was filtered
  2. customthe solid was dried under vacuum
  3. customThe solid was purified by column chromatography
  4. washeluting with dichloromethane:methanol (10:1 v/v) mixture
  5. customAfter solvent evaporation of the selected fractions
  6. additioncontaining the desired compound

Sources & evidence

ORD record
ord-17f13e132678443794a9d8023eee1cba
Source dataset
uspto-grants-2015_07
Patent number
US09086390B2

Reaction notes

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