Image may be NSFW.
Clik here to view.
AMORPHOUS FORM OF AFATINIB DIMALEATE
SUN PHARMACEUTICAL INDUSTRIES LIMITED
VERMA, Shyam Sunder; (IN).
SINGH, Shravan Kumar; (IN).
SINGH, Kaptan; (IN).
PRASAD, Mohan; (IN)
Afatinib dimaleate is a tyrosine kinase inhibitor, chemically designated as 2-butenamide, N-[4-[(3-chloro-4-fluorophenyl)amino]-7-[[(35)-tetrahydro-3-furanyl]oxy]-6-quinazolinyl]-4-(dimethylamino)-,(2£)-, (2Z)-2-butenedioate (1:2) having the structure depicted by Formula I.
Image may be NSFW.
Clik here to view.
Formula I
U.S. Patent Nos. RE43,431 and 6,251,912 provide processes for the preparation of afatinib dimaleate.
U.S. Patent No. 8,426,586 and PCT Publication Nos. WO 2012/121764 and WO
2013/052157 provide processes for the preparation of crystalline forms of afatinib and their salts.
Example: Preparation of an amorphous form of afatinib dimaleate
In a round bottom flask, a mixture of afatinib (3 g) and ethyl acetate (30 mL) was heated to about 65°C to obtain a turbid solution. In another round bottom flask, a mixture of maleic acid (1.6 g) and ethyl acetate (30 mL) was heated to about 50°C to obtain a clear solution. The maleic acid solution was added to the afatinib solution, and then the reaction mixture was heated at about 75°C to about 80°C. The reaction mixture was stirred at about 75°C to about 80°C for about 1 hour. The reaction mixture was cooled to about
20°C to obtain a sticky material. The sticky material was scratched with a spatula, and then the reaction mixture was further stirred at about 20°C to about 25°C for about 1 hour. The material obtained was filtered, and then washed with ethyl acetate (20 mL). The solid obtained was dried under vacuum at about 45°C to about 50°C for about 15 hours to obtain the amorphous form of afatinib dimaleate.
Yield: 2.5 g (56%)
Image may be NSFW.
Clik here to view.
Image may be NSFW.
Clik here to view.
Image may be NSFW.
Clik here to view.
Sun Pharma chief Dilip Shanghvi
///////
Filed under: PATENT, PATENTS Tagged: AFATINIB DIMALEATE, NEW PATENT, SUN PHARMACEUTICALS, WO2016001844 Image may be NSFW.
Clik here to view.
Image may be NSFW.Clik here to view.
Image may be NSFW.Clik here to view.
Image may be NSFW.Clik here to view.
Image may be NSFW.Clik here to view.
Image may be NSFW.Clik here to view.
Image may be NSFW.Clik here to view.
Image may be NSFW.Clik here to view.
