Erlotinib → Erlotinib Hydrochloride

HRID 1184636Notes

Reaction equation

HRID 1184636 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]2[C:20]([NH:21][C:22]3[CH:23]=[CH:24][CH:25]=[C:26]([C:28]#[CH:29])[CH:27]=3)=[N:19][CH:18]=[N:17][C:9]2=[CH:10][C:11]=1[O:12][CH2:13][CH2:14][O:15][CH3:16].[ClH:30].C(OCC)(=O)C>C(C(C)=O)C(C)C>[CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]2[C:20]([NH:21][C:22]3[CH:23]=[CH:24][CH:25]=[C:26]([C:28]#[CH:29])[CH:27]=3)=[N:19][CH:18]=[N:17][C:9]2=[CH:10][C:11]=1[O:12][CH2:13][CH2:14][O:15][CH3:16].[ClH:30]

Participants

4

Reactant 2

HCID 176870ErlotinibHCID 21866389Hydrogen chloride-ethyl acetate

Product 1

HCID 176871Erlotinib Hydrochloride

Reagents, catalysts & solvents 1

HCID 7909Methyl Isobutyl KetoneSolvent

Conditions

Temperature
27.5 °C

Procedure

Erlotinib free base (10 gm) is added to methyl isobutyl ketone (300 ml) under stirring at 25-30° C., the contents are heated to 60° C. and then stirred at 60-65° C. to form a clear solution. To the solution slowly added 7% ethyl acetate HCl (40 ml) at 60-65° C., the resulting mass is slowly cooled to 25-30° C. and then stirred for 1 hour. Filtered the mass, washed with methyl isobutyl ketone (20 ml) and then dried at 50-55° C. to give 9.8 gm of erlotinib hydrochloride crystalline polymorph form A having polymorph form B undetected (HPLC Purity: 99.87%, Moisture Content: 0.2%).

Workup

  1. temperaturethe contents are heated to 60° C.
  2. stirringstirred at 60-65° C.
  3. customto form a clear solution
  4. stirringstirred for 1 hour
  5. filtrationFiltered the mass
  6. washwashed with methyl isobutyl ketone (20 ml)
  7. customdried at 50-55° C.

Sources & evidence

ORD record
ord-8b4914c0feb048c4a4a374b56e5a53bd
Source dataset
uspto-grants-2014_03
Patent number
US08669265B2

Reaction notes

Loading…