Water → Temozolomide

HRID 1433130Notes

Reaction equation

HRID 1433130 reaction equation
O.[CH3:2][N:3]1[N:12]=[N:11][C:10]2[N:6]([CH:7]=[N:8][C:9]=2[C:13]([NH2:15])=[O:14])[C:4]1=[O:5].Cl>C(#N)C>[CH3:2][N:3]1[N:12]=[N:11][C:10]2[N:6]([CH:7]=[N:8][C:9]=2[C:13]([NH2:15])=[O:14])[C:4]1=[O:5]

Participants

4

Reactant 2

HCID 962WaterHCID 11658676Temozolomide hydrochloride

Product 1

HCID 5394TemozolomideYield 90.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
61.5 °C

Procedure

A 1.25 cm width column was filled with 10 grams of the ion exchange resin Lewatit Mono Plus™ MP-64. A solvent mixture comprising 55% water and 45% acetonitrile (20 ml) was added and 30 minutes were allowed for resin swelling. Then, the solution was allowed to drain up to the top of the resin and a solution of the mother liquor of example 1 (50 ml) was passed through the column at a rate of about 1 ml/1 min. The first volume was discarded (10 ml) and then the eluted solution (the eluate) was collected (50 ml) and transferred to a reaction vessel. Temozolomide hydrochloride (3.33 grams, 0.0144 moles) was added and the mixture was heated to 60-63° C. under stirring and filtered at this temperature. Then, the mixture was cooled to 5° C., and stirring was maintained for about 30 minutes to enable crystallization. The crystals thus obtained were collected by filtration and washed with water (2×10 ml) and cold acetone (10 ml). The crystals were dried at 40° C. in vacuum to obtain 2.52 grams (0.013 moles) of Temozolomide base in 90.3% yield. Purity (by HPLC): 99.9%.

Workup

  1. additionwas added and 30 minutes
  2. customwas passed through the column at a rate of about 1 ml/1 min
  3. customthe eluted solution (the eluate) was collected (50 ml)
  4. customtransferred to a reaction vessel
  5. filtrationfiltered at this temperature
  6. temperatureThen, the mixture was cooled to 5° C.
  7. stirringstirring
  8. temperaturewas maintained for about 30 minutes
  9. customcrystallization
  10. customThe crystals thus obtained
  11. filtrationwere collected by filtration
  12. washwashed with water (2×10 ml) and cold acetone (10 ml)
  13. customThe crystals were dried at 40° C. in vacuum

Sources & evidence

ORD record
ord-68cc807059f1409f9c227ff3db858e90
Source dataset
uspto-grants-2009_11
Patent number
US07612202B2

Reaction notes

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