Hydrochloric Acid → Topotecan Hydrochloride

HRID 1012045

Reaction equation

HRID 1012045 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].[Cl:28]CCl.Cl>C(O)(C)C.C(N(CC)CC)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[CH:20]=[CH:19][C:18]([OH:26])=[C:17]([CH2:10][N:12]([CH3:24])[CH3:13])[C:16]2=[CH:15][C:14]=1[CH2:13]3)=[O:11].[ClH:28]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 6344DichloromethaneHCID 97226Hydroxycamptothecin

Product 1

HCID 60699Topotecan HydrochlorideYield 238.7%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolvent2×HCID 8471TriethylamineSolvent

Conditions

Temperature
27.5 °C

Procedure

10-hydroxy-camptothecin (1.0 kg), dichloromethane (about 13 kg) and isopropanol (about 8 kg) were charged into a suitable reactor. N,N-dimethylmethyleneiminium chloride (0.3-0.5 kg) was added into the reactor. Triethylamine (0.04-0.2 kg) was then added into the resulting mixture at 20-35° C. and stirred at 20-35° C. for at least 12 hours. When the reaction was complete, a mixture of hydrochloric acid (32%, 0.06-0.3 kg) and isopropanol (about 5 kg) was added into the resulting mixture. After the addition was completed, the resulting mixture was stirred, filtered, and then washed with dichloromethane (about 3 kg). The wet solids were dried to give about 1.5 kg of crude topotecan HCl.

Workup

  1. additionwas added into the resulting mixture
  2. additionAfter the addition
  3. stirringthe resulting mixture was stirred
  4. filtrationfiltered
  5. washwashed with dichloromethane (about 3 kg)
  6. customThe wet solids were dried

Sources & evidence

ORD record
ord-a990f31caf2b42d798fbefd3670a4b58
Source dataset
uspto-grants-2011_07
Patent number
US07977483B2

Linked notes

Loading…