Water → Dabigatran Impurity 8

HRID 1527153Notes

Reaction equation

HRID 1527153 reaction equation
CCCCCC[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][CH2:38][CH3:39])=[O:36])=[O:31])=[CH:23][C:22]=3[N:21]=2)=[CH:16][CH:17]=1)=[O:9].CS(O)(=O)=O.[OH2:52]>>[CH2:14]([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:22]=[CH:23][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][CH2:38][CH3:39])=[O:36])=[O:31])=[CH:25][C:26]=3[N:21]=2)=[CH:16][CH:17]=1)=[O:52])=[O:9])[CH2:13][CH2:12][CH2:17][CH2:16][CH3:15]

Participants

4

Reactant 3

HCID 962WaterHCID 6395Methanesulfonic AcidHCID 6445226ethyl 3-(2-((4-(N-(hexyloxycarbonyl)carbamimidoyl)phenylamino)methyl)-1-methyl-N-(pyridin-2-yl)-1H-benzo[d]imidazole-5-carboxamido)propanoate

Product 1

HCID 70968095Dabigatran Impurity 8

Conditions

Temperature
50 °C

Procedure

32 g of dabigatran etexilate were suspended in 320 mL of deionized water. 5.4 g of methanesulfonic acid were added. The reaction mixture was heated to 50° C. and stirred at this temperature for 72 hours. The resulting mixture was filtered, and the solid was dried under vacuum. The solid was purified by column chromatography, eluting with ethyl acetate:methanol (15:1 v/v) mixture. After solvent evaporation of the selected fractions containing the desired compound, 15 g of ethyl 3-{[(2-{[(4-{[({hexyloxy}carbonyl)amino]carbonyl}-phenyl)amino]methyl}-1-methyl-1H-benzimidazol-5-yl)carbonyl](pyridin-2-yl)amino}propanoate 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 ethyl acetate:methanol (15:1 v/v) mixture
  5. customAfter solvent evaporation of the selected fractions
  6. additioncontaining the desired compound

Sources & evidence

ORD record
ord-ea7f9fe5768543798c71ca9dd66d4ea6
Source dataset
uspto-grants-2015_07
Patent number
US09086390B2

Reaction notes

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