Acetic Acid → Erlotinib Hydrochloride

HRID 238998

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.[NH2:22][C:23]1[CH:24]=[C:25]([C:29]#[CH:30])[CH:26]=[CH:27][CH:28]=1.C(O)(=O)C>C(#N)C>[CH3:16][O:15][CH2:14][CH2:13][O:12][C:9]1[CH:10]=[C:11]2[C:2]([NH:22][C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([C:29]#[CH:30])[CH:24]=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

Conditions

Temperature: 27.5 °C

Procedure

50 g of 4-chloro-6,7-bis(2-methoxyethoxy) quinazoline was suspended in 1500 ml acetonitrile and 46 g of 3-aminophenyl acetylene was added at 25-30° C., followed by 10 ml acetic acid. The reaction mass was stirred at 25-30° C. for 30 minutes. Solid obtained was filtered, washed with water and dried under vacuum. This solid was suspended in water, basified with potassium hydroxide and stirred for 10 minutes. The resulting erlotinib base was isolated, washed with acetonitrile and dried under vacuum. The solid obtained was then suspended in water and acidified to pH 1.0-2.0 using hydrochloric acid. The reaction mixture was stirred for 2 hours, filtered, washed with water and dried at 40-45° C. to obtain 63 g of erlotinib hydrochloride.

Workup

customSolid obtained
filtrationwas filtered
washwashed with water
customdried under vacuum
stirringstirred for 10 minutes

Sources & evidence

ORD record: ord-104de0332f164e28ac2ab9cfac85625f
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08642758B2

Linked notes

Loading…