Water → BendaMustine IMpurity C

HRID 2207000Notes

Reaction equation

HRID 2207000 reaction equation
[CH:1]([O:4][C:5](=[O:26])[CH2:6][CH2:7][CH2:8][C:9]1[N:13]([CH3:14])[C:12]2[CH:15]=[CH:16][C:17]([N:19]([CH2:23]CO)[CH2:20][CH2:21]O)=[CH:18][C:11]=2[N:10]=1)([CH3:3])[CH3:2].Cl[CH2:28][Cl:29].S(Cl)([Cl:32])=O.O>CCCCCCC>[CH:1]([O:4][C:5](=[O:26])[CH2:6][CH2:7][CH2:8][C:9]1[N:13]([CH3:14])[C:12]2[CH:15]=[CH:16][C:17]([N:19]([CH2:23][CH2:28][Cl:29])[CH2:20][CH2:21][Cl:32])=[CH:18][C:11]=2[N:10]=1)([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 6344Dichloromethane2×HCID 24386Thionyl ChlorideHCID 53258885HCID 53258885, compound

Product 1

HCID 53258886BendaMustine IMpurity C

Reagents, catalysts & solvents 1

HCID 8900HeptaneSolvent

Conditions

Temperature
28 °C

Procedure

4-{5-[Bis-(2-hydroxyethyl)amino]-1-methyl-1H-benzimidazol-2-yl}-butyric acid isopropyl ester (5 g) and dichloromethane (50 mL) are charged into a round bottom flask and stirred at 28° C. Thionyl chloride (2.6 mL, 2.6 M) is slowly added at the same temperature and the reaction mass is allowed to settle for 30 minutes. The reaction mixture is heated to a temperature of 38-40° C. and the mixture is stirred for 90 minutes. Cooled the reaction mass to 25-30° C., dichloromethane layer (25 mL) and water (25 mL) are added and stirred. Separated the organic layer and washed with saturated sodium bicarbonate solution (25 mL) and saturated brine solution (25 mL). The organic layer is concentrated under vacuum at 45° C. to obtain 10-15 mL of the concentrated mass, cooled the mass to 25-30° C. N-heptane (62.5 mL) is added to the mass slowly at 28° C., stirred for about 1 hour, filtered and dried under vacuum to give 4-{5-[bis-(2-chloroethyl)amino]-1-methyl 1H-benzoimidazol-2-yl}-butyric acid isopropyl ester compound. Yield: 4.4 g.

Workup

  1. temperatureThe reaction mixture is heated to a temperature of 38-40° C.
  2. stirringthe mixture is stirred for 90 minutes
  3. temperatureCooled the reaction mass to 25-30° C.
  4. stirringstirred
  5. customSeparated the organic layer
  6. washwashed with saturated sodium bicarbonate solution (25 mL) and saturated brine solution (25 mL)
  7. concentrationThe organic layer is concentrated under vacuum at 45° C.
  8. customto obtain 10-15 mL of the concentrated mass
  9. temperaturecooled the mass to 25-30° C
  10. stirringstirred for about 1 hour
  11. filtrationfiltered
  12. customdried under vacuum

Sources & evidence

ORD record
ord-c649f69b788a46ad8347d5d9bc447bc1
Source dataset
uspto-grants-2016_06
Patent number
US09376394B2

Reaction notes

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