Acetic Acid → Temozolomide

HRID 1433129Notes

Reaction equation

HRID 1433129 reaction equation
[CH3:1][N:2]1[N:11]=[N:10][C:9]2[N:5]([CH:6]=[N:7][C:8]=2[C:12]([NH2:14])=[O:13])[C:3]1=[O:4].Cl.C1COCC1.C(O)(=O)C>O>[CH3:1][N:2]1[N:11]=[N:10][C:9]2[N:5]([CH:6]=[N:7][C:8]=2[C:12]([NH2:14])=[O:13])[C:3]1=[O:4]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 8028TetrahydrofuranHCID 11658676Temozolomide hydrochloride

Product 1

HCID 5394TemozolomideYield 70%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
5 °C

Procedure

A 250 ml reaction vessel equipped with a magnetic stirrer and a reflux condenser was charged with Temozolomide hydrochloride (2.9 grams, 0.0126 mol), THF (23 ml), acetic acid (0.7 ml) and water (28.8 ml). The reaction mixture was heated to reflux and stirring was maintained at this temperature for about 10 minutes. The reaction mixture was filtered at elevated temperature and then cooled to 5° C. for about half an hour to enable crystallization. The crystals thus obtained were collected and washed with water (2×20 ml) and cold acetone (20 ml). The crystals were dried at 40° C. in vacuum to obtain 1.71 grams (0.0088 mol) of free Temozolomide base (70% yield). Purity (by HPLC): 99.8%.

Workup

  1. customA 250 ml reaction vessel
  2. customequipped with a magnetic stirrer and a reflux condenser
  3. temperatureThe reaction mixture was heated
  4. temperatureto reflux
  5. temperaturewas maintained at this temperature for about 10 minutes
  6. filtrationThe reaction mixture was filtered at elevated temperature
  7. customcrystallization
  8. customThe crystals thus obtained
  9. customwere collected
  10. washwashed with water (2×20 ml) and cold acetone (20 ml)
  11. customThe crystals were dried at 40° C. in vacuum

Sources & evidence

ORD record
ord-95695c936eff4bc69c9431a7db1f8696
Source dataset
uspto-grants-2009_11
Patent number
US07612202B2

Reaction notes

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