Flibanserin hydrochloride

Add 871mL methanol, 43.6mL concentrated hydrochloric acid, stir and heat up to reflux and keep the reaction stirred for 10min, slowly cool to room temperature, crystallization for 5 hours, filtration, 40 C blast drying for 5 hours to obtain compound V (Flibanserin hydrochloride) 84. 1 g, yield 78.8% (as in compound I), HPLC purity 99. 92%.44 L of ethanol and 300 kg of water were added to the autoclave, followed by the addition of 22 kg of compound V (fluoropancaline hydrochloride)After heating, the temperature was 80 C. After the solid was completely dissolved, the anhydrous potassium carbonate solution (11. 7 kg of anhydrous potassium carbonate was dissolved in 96 kg of water) was added dropwise and incubated at 80 C for 2 hours.Cooled to room temperature, stirred for 3 hours, filtered, filtered at 50 C for 5 hours, Finished product 18. 61 kg, yield 92.5%, HPLC purity 99. 95%Synthesis of the salt forms; The process is illustrated by the following example of manufacturing process of the salts and crystalline salt forms, as can be done in parallel in 96 well assay plates (maximum volume of each well is about 200 mul).; Approximately 1 g of the free base of flibanserin were dissolved in 10 mlTFE/water 80:20. The acids used to prepare the salts were dissolved in different solvents such that the molar ratio of the flibanserin to the respective acid was set according to the information given in Table 3 under 'ratio base/acid. Fumaric acid was dissolved in THF/water 80:20, HCI in water and all other acids used were dissolved in TFE/water 80:20. However it is to mention that all other solvents which are able to dissolve the acid used could have been used. The 96 well plates were then placed in a vacuum chamber (1 kPa) at room temperature for 24 h in order to evaporate the solvent. Afterwards, different solvents were added in each well according to the information given in Table 3 under 'crystallization' solvent, and the well plates were sealed and heated up to 50 0C at a heating rate of approx. 5 C/min. The plate stayed then for an additional 30 minutes at 50 0C. Afterwards, the plate was cooled at a cooling rate of 5C/h to a final temperature of 3 or 20 0C according to the information given in Table 3 under 'Tfinaiota[oC]'. At this temperature, the plates remained for a holding time of 24 h. The plates were then opened and the solids were collected by filtration. All salts specified in table 3 were synthesized according to the above specification.Example 2To a mixture of flibanserin (10 gm) and isopropanol (50 ml), adjusted pH to 2 with isopropanolic hydrochloric acid solution (12 ml) at room temperature.The reaction mass was stirred for 2 hours at room temperature and filtered, washed with isopropanol and dried at 80 to 850C for 2 hours to obtain 9 gm of

Molecular Weight:426.9
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:6
Rotatable Bond Count:4
Exact Mass:426.1434235
Monoisotopic Mass:426.1434235
Topological Polar Surface Area:38.8
Heavy Atom Count:29
Complexity:550
Covalently-Bonded Unit Count:2
Compound Is Canonicalized:Yes