Hydrochloric Acid → Erlotinib Hydrochloride

HRID 1801710Notes

Reaction equation

HRID 1801710 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[C:10]2[C:12]([NH:16][C:17]3[CH:22]=[C:21]([C:23]#[CH:24])[CH:20]=[CH:19][CH:18]=3)=[N:13][CH:14]=[N:15][C:9]2=[CH:8][C:7]=1[O:25][CH2:26][CH2:27][O:28][CH3:29].[ClH:30]>C(Cl)Cl>[CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[C:10]2[C:12]([NH:16][C:17]3[CH:18]=[CH:19][CH:20]=[C:21]([C:23]#[CH:24])[CH:22]=3)=[N:13][CH:14]=[N:15][C:9]2=[CH:8][C:7]=1[O:25][CH2:26][CH2:27][O:28][CH3:29].[ClH:30]

Participants

4

Reactant 2

HCID 313Hydrochloric Acid2×HCID 176870Erlotinib2×

Product 1

HCID 176871Erlotinib Hydrochloride

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Into a 3 Lt. four necked round-bottomed flask provided with a mechanical stirrer, thermometer socket, reflux condenser etc, are charged 2400 mL of methylene chloride, followed by 120 g of Erlotinib base (Prepared according to the process given in Example-(1) of PCT international publication No. WO2007/060691) under stirring. The reaction mass is slightly warmed up to 37±1° C., so that the Erlotinib base completely dissolves in the solvent. Then carbon treatment is given and the filtrate is transferred to 5 Lt three necked round bottomed flask, provided with a mechanical stirrer and other accessories. To this filtrate, Isopronolic HCl. (HCl content as 100% is 13.90 g) is added in one lot at 30-35° C. and then the reaction mass is refluxed for about 3 hrs. Afterwards, the reaction mass is cooled to room temperature and filtered. The product is washed with methylene chloride and the wet cake is dried to get 119 g of Erlotinib hydrochloride as a white crystalline powder.

Workup

  1. customfour necked round-bottomed flask provided with a mechanical stirrer
  2. temperaturethermometer socket, reflux condenser etc
  3. customPrepared
  4. dissolutioncompletely dissolves in the solvent
  5. customprovided with a mechanical stirrer
  6. temperaturethe reaction mass is refluxed for about 3 hrs
  7. filtrationfiltered
  8. washThe product is washed with methylene chloride
  9. customthe wet cake is dried

Sources & evidence

ORD record
ord-7d73cacae5cc43169a54e50b66d7c9bf
Source dataset
uspto-grants-2013_01
Patent number
US08349855B2

Reaction notes

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