Water → BendaMustine IMpurity C

HRID 2206998Notes

Reaction equation

HRID 2206998 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 6344DichloromethaneHCID 24386Thionyl ChlorideHCID 53258885HCID 53258885, compound

Product 1

HCID 53258886BendaMustine IMpurity C

Reagents, catalysts & solvents 1

HCID 8900HeptaneSolvent

Conditions

Temperature
2.5 °C

Procedure

4-{5-[Bis-(2-hydroxyethyl)amino]-1-methyl-1H-benzimidazol-2-yl}-butyric acid isopropyl ester (5 g) and dichloromethane (75 mL) are charged into a round bottom flask and cooled to 0-5° C. Thionyl chloride (4 mL, 4.0 M) is slowly added at the same temperature. The temperature is allowed to rise to 25-30° C. and the mixture is stirred for about 7 hours. Water (100 mL) is slowly added and the mixture is stirred for about 20 minutes, then the layers are separated. The dichloromethane layer is washed with saturated sodium bicarbonate solution (100 mL), dried over sodium sulfate, and is concentrated under vacuum at 30-33° C. to obtain 10-15 mL of a concentrated mass. n-Heptane (100 mL) is added to the concentrated mass slowly at 27° C., stirred for about 1 hour, filtered, and the collected solid is washed with n-heptane (15 mL) and dried under vacuum to give the title compound. Yield: 3.4 g (61%).

Workup

  1. customto rise to 25-30° C.
  2. stirringthe mixture is stirred for about 20 minutes
  3. customthe layers are separated
  4. washThe dichloromethane layer is washed with saturated sodium bicarbonate solution (100 mL)
  5. dry with materialdried over sodium sulfate
  6. concentrationis concentrated under vacuum at 30-33° C.
  7. customto obtain 10-15 mL of a concentrated mass
  8. stirringstirred for about 1 hour
  9. filtrationfiltered
  10. washthe collected solid is washed with n-heptane (15 mL)
  11. customdried under vacuum

Sources & evidence

ORD record
ord-bb1f01cb314e4b13b71aa078b37d4372
Source dataset
uspto-grants-2016_06
Patent number
US09376394B2

Reaction notes

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