Acetone → Topotecan Acetate

HRID 1986022Notes

Reaction equation

HRID 1986022 reaction equation
[CH3:1][CH2:2][C@@:3]1([OH:27])[C:8](=[O:9])[O:7][CH2:6][C:5]2[C:10]([N:12]3[C:24](=[CH:25][C:4]1=2)[C:23]1[N:22]=[C:21]2[C:16]([CH:17]=[C:18]([OH:26])[CH:19]=[CH:20]2)=[CH:15][C:14]=1[CH2:13]3)=[O:11].[CH3:28][NH:29][CH3:30].C=O.[CH3:33]C(C)=O>C(O)(=O)C>[CH3:1][CH2:2][C@@:3]1([OH:27])[C:8](=[O:9])[O:7][CH2:6][C:5]2[C:10]([N:12]3[C:24](=[CH:25][C:4]1=2)[C:23]1[N:22]=[C:21]2[C:16](=[CH:15][C:14]=1[CH2:13]3)[C:17]([CH2:28][N:29]([CH3:33])[CH3:30])=[C:18]([OH:26])[CH:19]=[CH:20]2)=[O:11].[CH3:3][C:8]([OH:9])=[O:7]

Participants

6

Reactant 4

HCID 180AcetoneHCID 674DimethylamineHCID 712FormaldehydeHCID 97226Hydroxycamptothecin2×

Product 1

HCID 14761101Topotecan Acetate

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
45.29999923706055 °C

Procedure

0.3 Kg of 10-hydroxy camptothecin (Formula IV) prepared according to Example-1 was suspended in 6 L of acetic acid and stirred for 5 minutes. The obtained solution was charged into a reactor and stirred for 20 minutes. 0.51 L of a 40% aqueous solution of dimethyl amine and 0.078 L of a 37% of aqueous solution of formaldehyde were charged into the reactor, the temperature raised to 45.3° C. and the reaction mixture stirred for 2 hours at 45.3° C. The reaction solution was allowed to cool to 34.8° C. and then cooled to 27.5° C. 42 L of acetone was charged into above reaction solution and stirred for 1 hour at 27.5° C. for complete precipitation. The formed solid was filtered and the reactor rinsed with 1.5 L of acetone. The wet solid was washed with the rinsing and then washed with 0.3 L of 1-propanol. The resultant solid was suction dried for 20 minutes and then dried for 5 hours at 52° C. under a vacuum of 690 mm Hg to afford 330 g of title compound having a purity by HPLC of about 98.9%.

Workup

  1. additionThe obtained solution was charged into a reactor
  2. stirringstirred for 20 minutes
  3. stirringthe reaction mixture stirred for 2 hours at 45.3° C
  4. temperatureto cool to 34.8° C.
  5. temperaturecooled to 27.5° C
  6. stirringstirred for 1 hour at 27.5° C. for complete precipitation
  7. filtrationThe formed solid was filtered
  8. washthe reactor rinsed with 1.5 L of acetone
  9. washThe wet solid was washed with the rinsing and
  10. washthen washed with 0.3 L of 1-propanol
  11. customThe resultant solid was suction dried for 20 minutes
  12. customdried for 5 hours at 52° C. under a vacuum of 690 mm Hg

Sources & evidence

ORD record
ord-ed3f6535216e44a0a257aede8a93e8a0
Source dataset
uspto-grants-2009_06
Patent number
US07547785B2

Reaction notes

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