Benzenamine, 3-ethynyl- → Erlotinib Hydrochloride

HRID 1184632Notes

Reaction equation

HRID 1184632 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:17][CH2:18][CH2:19][O:20][CH3:21])=[C:9]([O:12][CH2:13][CH2:14][O:15][CH3:16])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[C:22]([C:24]1[CH:25]=[C:26]([CH:28]=[CH:29][CH:30]=1)[NH2:27])#[CH:23]>C(O)C>[CH3:16][O:15][CH2:14][CH2:13][O:12][C:9]1[CH:10]=[C:11]2[C:2]([NH:27][C:26]3[CH:28]=[CH:29][CH:30]=[C:24]([C:22]#[CH:23])[CH:25]=3)=[N:3][CH:4]=[N:5][C:6]2=[CH:7][C:8]=1[O:17][CH2:18][CH2:19][O:20][CH3:21].[ClH:1]

Participants

4

Reactant 2

HCID 104682Benzenamine, 3-ethynyl-HCID 112899424-Chloro-6,7-bis(2-methoxyethoxy)quinazoline

Product 1

HCID 176871Erlotinib HydrochlorideYield 101.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
27.5 °C

Procedure

4-Chloro-6,7-bis-(2-methoxyethoxy)-quinazoline (2.5 gm) and ethanol (40 ml) are added to 3-ethynylaniline (1.25 gm) at 25-30° C. under stirring, the contents are heated to reflux and then refluxed for 1 hour 30 minutes to 2 hours. The reaction mass is cooled to 25-30° C. and stirred for 30 minutes. Filtered the material, washed with chilled isopropyl alcohol (20 ml) followed by n-hexane (20 ml) and then dried the material at 50-55° C. under vacuum to give 3.5 gm of crude erlotinib hydrochloride in polymorph form B [HPLC purity: 99.1%; Mean particle size (D50): 2.30 nm and 90 volume-% of the particles (D90): 7.74 μm].

Workup

  1. temperaturethe contents are heated
  2. temperatureto reflux
  3. temperaturerefluxed for 1 hour 30 minutes to 2 hours
  4. stirringstirred for 30 minutes
  5. filtrationFiltered the material
  6. washwashed with chilled isopropyl alcohol (20 ml)
  7. customdried the material at 50-55° C. under vacuum

Sources & evidence

ORD record
ord-7935819d1d21430090e08963866251d5
Source dataset
uspto-grants-2014_03
Patent number
US08669265B2

Reaction notes

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