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1 Preparation of N-[4-(3-chloro-4-fluorophenylamino)-7-(3-morpholin-4-ylpropoxy)-quinazolin-6-yl]-acrylamide Dihydrochloride Form M.
EXAMPLE 1 Preparation of N-[4-(3-chloro-4-fluorophenylamino)-7-(3-morpholin-4-ylpropoxy)-quinazolin-6-yl]-acrylamide Dihydrochloride Form M. A 6 l three-necked flask equipped wich a mechanical stirrer, a reflux condenser and a dropping funnel is supplied with 300 g N-[4-(3-chloro-4-fluorophenylamino)-7-(3-morpholin-4-ylpropoxy)-quinazolin-6-yl]-acrylamide and 4 l abs. ethanol. With stirring, the suspension is heated to 35° C. A mixture of 100 ml conc. hydrochloric acid and 100 ml water is then added dropwise thereto within 30 s and the reaction mixture further heated to 74° C. At 40° C, a clear solution results, at about 50° C. the solution becomes turbid and the crystallisation commences. With stirring, one allows the reaction mixture to cool slowly to room temperature and then cools further in an icebath for 2 h to 2° C. The precipitated crystals are filtered off with suction and dried in a circulating drying cabinet for 40 h at 60° C. Thereafter, the product is carefully sieved through a 0.5 mm Kressner sieve. One obtains 314.2 g of product. Water according to Karl Fischer: 2.84%. Elementary analysis: (C24H25ClFNSO3*2HCl*H2O)
3 Preparation of N-[4-(3-chloro-4-fluorophenylamino)-7-(3-morpholin-4-ylpropoxy)-quinazolin-6-yl]-acrylamide Dihydrochloride Form B
EXAMPLE 3 Preparation of N-[4-(3-chloro-4-fluorophenylamino)-7-(3-morpholin-4-ylpropoxy)-quinazolin-6-yl]-acrylamide Dihydrochloride Form B A Suspension of 250 g N-[4-(3-chloro-4-fluorophenylamino)-7-(3-morpholin-4-ylpropoxy)-quinazlon-6-yl]-acrylamide dihydrochloride form A in 2.6 l water is heated, with stirring, to 50° C. The slightly turbid solution is sucked through a Buchner funnel (porosity a) and the filtrate cooled to room temperature without stirring. After standing overnight in a refrigerator at 4° C., the precipitated product is filtered off with suction, washed out with 100 ml water and dried in a vacuum desiccator over calcium chloride at 20 mbar for 3 days. The product obtained is sieved over a 1 mm Kresner sieve. One obtains 212.2 g of product. Water according to Karl Fischer: 8.6% Elementary analysis: (C24H2ClFN5O3*2HCl*3H2O)
4 Preparation of N-[4-(3-chloro-4-fluorophenylamino)-7-(3-morpholin-4-ylpropoxy)-quinazolin-6-yl]-acrylamide Dihydrochloride Form H
EXAMPLE 4 Preparation of N-[4-(3-chloro-4-fluorophenylamino)-7-(3-morpholin-4-ylpropoxy)-quinazolin-6-yl]-acrylamide Dihydrochloride Form H 2 g N-[4-(3-Chloro-4-fluorophenylamino)-7-(3-morpholin-4-ylpropoxy)-quinazolin-6-yl]-acrylamide dihydrochloride form B are dissolved in 80 ml abs. methanol at room temperature. The solution is filtered into a crystallisation dish and kept open under an extractor up to the complete evaporation of the solvent (7 days). Water according to Karl Fischer: 19.95% Elementary analysis: (C24H2ClFNFO3*2HCl*7H2O)