Water → Ethyl 5-(bis(2-hydroxyethyl)amino)-1-methyl-1H-benzimidazole-2-butanoate
Reaction equation
[CH3:1][N:2]1[C:17]([CH2:18][CH2:19][CH2:20][C:21]([OH:23])=[O:22])=[N:16][C:4]2[CH:5]=[C:6]([N:9]([CH2:13][CH2:14]Cl)[CH2:10][CH2:11]Cl)[CH:7]=[CH:8][C:3]1=2.[OH2:24].Cl.[CH2:26]1O[CH2:27]1.[OH2:29].C([O-])(=O)C.[Na+]>C(O)(=O)C>[CH2:26]([O:23][C:21](=[O:22])[CH2:20][CH2:19][CH2:18][C:17]1[N:2]([CH3:1])[C:3]2[CH:8]=[CH:7][C:6]([N:9]([CH2:13][CH2:14][OH:29])[CH2:10][CH2:11][OH:24])=[CH:5][C:4]=2[N:16]=1)[CH3:27]Participants
Conditions
- Temperature
- 20 °C
Procedure
Li-Mei et al., in Zhongguo Xinyao Zazhi (2007), 16(23), 1960-1961, 1970 disclose a process for the preparation of bendamustine hydrochloride monohydrate, which involves reacting [1-methyl-2-(4′-ethyl butyrate)-5-amino]-1H-benzimidazole with ethylene oxide in the presence of water, sodium acetate and acetic acid, by maintaining at 5° C. for 5 hours and overnight at 20° C. to give (4-{5-[bis-(2-hydroxy-ethyl)-amino]-1-methyl-1H-benzimidazol-2-yl}-butyric acid ethyl ester as a jelly mass, which on chlorination using thionyl chloride in chloroform and in situ hydrolysis with concentrated HCl at 90-95° C. gave bendamustine hydrochloride. It also discloses a process for the recrystallization of bendamustine hydrochloride from water and the product obtained is a monohydrate with a melting point of 148-151° C.
Sources & evidence
- ORD record
- ord-c8eddc4bec9b41e8b12b71ea6489b9c6
- Source dataset
- uspto-grants-2016_06
- Patent number
- US09376394B2
Reaction notes
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