UNII-MGN125FS9D

Regorafenib monohydrate is a multi-target inhibitor for VEGFR1/2/3, PDGFRβ, Kit, RET and Raf-1 with IC50s of 13/4.2/46, 22, 7, 1.5 and 2.5 nM, respectively.

Regorafenib hydrate is a hydrate that is the monohydrate form of anhydrous regorafenib. Used for for the treatment of metastatic colorectal cancer in patients who have previously received chemotherapy, anti-EGFR or anti-VEGF therapy. It has a role as an antineoplastic agent, a tyrosine kinase inhibitor and a hepatotoxic agent. It contains a regorafenib.

Preparation of ^H-fU^chloro-S-ftrifluoroinethvQphenyllcarbairtovUa'iinoVS- fluorophenoxyl-N-iotanethylnyridiotane-2-carboxamide in the polymorph TIIExample 2.13.5 g of the compound according to are tempered for 60 min at 1000C and further 15 min at 1 10C. After cooling to room temperature the product is tested by X-ray diffractometry and corresponds to the title compound. Example 2.29 mg of the compound according to are heated to 1000C in a Thermogravimetric Analyser (TGA) and are tempered for 10 min at that temperature. After cooling to room temperature the product is tested by X-ray diffractometry and corresponds to the title compound.Example 2.3 50 mg of the compound according to are tempered for 10 min at 1 100C. After cooling to room temperature the product is tested by X-ray diffractometry and corresponds to the title compound. EPO 400 mg of 4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-N- methylpyridine-2-carboxamide in the polymorph I, prepared as described in WO 2005/009961, are dissolved in acetone and the solution is filtered. Water is added to one fourth of the filtrate until precipitation. The precipitate is filtered and dried at room temperature under ambient humidity. The sample is tested gravimetrically and corresponds to the title compound.100 mg of 4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-N- methylpyridine-2-carboxamide in the polymorph I, prepared as described in WO 2005/009961, are suspended in 2 ml of a mixture of acetonitril-water (1 :1) and shaken at 25C. After one week the suspension is filtered and the residue is dried at room temperature and ambient humidity. The residue is tested gravimetrically and corresponds to the title compound.400 mg of 4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-N- methylpyridine-2-carboxamide in the polymorph I, prepared as described in WO 2005/009961, are dissolved in 50 ml of ethanol and the solution is filtered. One fourth of the solution is stayed in the freezer for crystallization at about -2O0C until the solvent is evaporated. The residue is tested by X- ray diffractometry and corresponds to the title compound.100 mg of 4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-N- methylpyridine-2-carboxamide in the polymorph I, prepared as described in WO 2005/009961, are suspended in 2 ml of a mixture of tetrahydrofuran-water (1 :1) and stirred at 100C. After two weeks : Preparation of 'l-N-df't-chloro-S-ftrifliioromethyDphenyllcarbamoyUaniinoVS- fluoroplienoxyl-N-methylpyridine-2-carboxamide monohydrate Example 1.1; 400 mg of 4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-N- methylpyridine-2-carboxamide in the polymorph I, prepared as described in WO 2005/009961, are dissolved in acetone and the solution is filtered. Water is added to one fourth of the filtrate until precipitation. The precipitate is filtered and dried at room temperature under ambient humidity. The sample is tested gravimetrically and corresponds to the monohydrate of the title compound.Example 1.3; 100 mg of 4-[4-({[4-chloro-3-(trifluoromethy])phenyl]carbamoyl}amino)-3-fluorophenoxy]-N- rnethylpyridine-2-carboxamide in the polymorph , prepared as described in WO 2005/009961 , are suspended in 2 ml of a mixture of acetonitril-water (1 : 1) and shaken at 25C. After one week the suspension is filtered and the residue is dried at room temperature and ambient humidity. The residue is tested gravimetrically and corresponds to the monohydrate of the title compound..2; 400 mg of 4-[4-({[4-chloro-3-(trifluoiOitauiotaethyl)plienyl]carbamoyl) amino)-3-fiuororhohenoxy]-N- methylpyridine-2-carboxamide in the polymorph T, prepared as described in WO 2005/009961 , arc dissolved in 50 ml of ethanol and the solution is filtered. One fourth of the solution is stayed in the freezer for crystallization at about -200C until the solvent is evaporated. The residue is tested by X- ray diffractometry and corresponds to the monohydrate of the title compound.Example 1.4; 100 mg of 4-[4-({[4-chloro-3-(trifiuoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-N- methylpyridine-2-carboxamide in the polymorph I, prepared as described in WO 2005/009961 , are suspended in 2 ml of a mixture of tetrahydrofuran-water ( 1 : 1 ) and stirred at 100C. After two weeks EPO

Molecular Weight:500.8
Hydrogen Bond Donor Count:4
Hydrogen Bond Acceptor Count:9
Rotatable Bond Count:5
Exact Mass:500.0874454
Monoisotopic Mass:500.0874454
Topological Polar Surface Area:93.4
Heavy Atom Count:34
Complexity:686
Covalently-Bonded Unit Count:2
Compound Is Canonicalized:Yes