Benzenamine, 3-ethynyl- → Erlotinib Hydrochloride
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]>CO>[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
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 37.5 °C
Procedure
4-chloro-6,7-bis-(2-methoxyethoxy)quinazoline (50 g, 0.1598 mol) was added to methanol (900 ml, 18 vol.) and the mixture was heated to 35-40° C. to obtain a uniform suspension. 3-Ethynylaniline (20.6 g, 0.1758 mol) was mixed with 100 ml (2 vol.) of methanol and added drop wise into the uniform suspension of 4-chloro-6,7-bis-(2-methoxyethoxy)quinazoline over a period of 15 min at 35-40° C. The temperature of the reaction mixture was slowly raised to 60-65° C. and maintained for 2-3 hours. The reaction was monitored by TLC as well as HPLC. When the 4-chloro-6,7-bis-(2-methoxyethoxy)-quinazoline content in the reaction mixture was not more than 3%, the reaction mixture was cooled to 25-30° C. and crude erlotinib hydrochloride was isolated by filtration. The cake was washed with 100 ml (2 vol.) of methanol and suck dried.
Workup
- customto obtain a uniform suspension
- additionadded drop
- temperatureThe temperature of the reaction mixture was slowly raised to 60-65° C.
- temperaturemaintained for 2-3 hours
- temperaturethe reaction mixture was cooled to 25-30° C.
Sources & evidence
- ORD record
- ord-dd56e7e12ead401088c6fedd5d312af5
- Source dataset
- uspto-grants-2015_02
- Patent number
- US08952022B2
Reaction notes
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