Browse Prior Art Database

Process for the preparation of afatinib.

IP.com Disclosure Number: IPCOM000243542D
Publication Date: 2015-Sep-30
Document File: 3 page(s) / 69K

Publishing Venue

The IP.com Prior Art Database

Abstract

The present disclosure relates to a process for the preparation of afatinib or its pharmaceutically acceptable salts that employs novel intermediates

This text was extracted from a Microsoft Word document.
At least one non-text object (such as an image or picture) has been suppressed.
This is the abbreviated version, containing approximately 53% of the total text.

PROCESS FOR THE PREPARATION OF AFATINIB

The present disclosure relates to a process for the preparation of afatinib or its pharmaceutically acceptable salts that employs novel intermediates.

Afatinib dimaleate is an orally administered irreversible inhibitor of both the epidermal growth factor receptor (EGFR) and human epidermal receptor 2 (HER2) tyrosine kinases. Afatinib dimaleate is used to treat patients with several solid tumors including non-small cell lung cancer (NSCLC), breast, head and neck cancer, and a variety of other cancers.

GILOTRIF® tablets contain afatinib, a tyrosine kinase inhibitor which is a 4-anilinoquinazoline. Afatinib is presented as the dimaleate salt, with the chemical name 2-butenamide, N-[4-[(3-chloro-4-fluorophenyl)amino]7-[[(3S)-tetrahydro-3-furanyl] -oxy]-6-quinazolinyl]-4-(dimethylamino)-,(2E)-, (2Z)-2-butenedioate (1:2). Its structural formula is:

The present disclosure is to provide a process for the preparation of afatinib or its pharmaceutically acceptable salts, which is as shown in scheme-I.

Scheme-I

Experimental details

Preparation of 7-Chloro-4-(3-chloro-4-Fluoro phenyl amino)-6-Nitro quinazoline (4):

5.0g of 7-Chloro-4-Hydroxy-6-Nitro-Quinazoline, Acetonitrile (20ml), POCl3 (5.0ml) to this added TEA (7.5ml) and heated to 70-800C for 3hrs then added 3-Cloro-4-Fluoro aniline (3.39g) solution in 15ml acetonitrile. Maintained for 1hr and volatile parts were recovered by distillation to that added toluene 35ml cooled to 100C and added sodium hydroxide solution in water 7.9g in 50ml followed by water 20ml. Product filtered and washed with water 50m...