PROCESS FOR PREPARING AN AMORPHOUS FORM OF CLASCOTERONE

Description

“ ” – lascoterone, also known as cortexolone 17α an action on glucose metabolism, promoting the availability of glucose in circulation inhibiting the use of the latter by peripheral tissues 10 and the NF system inhibitor Although the exact mechanism of action of the In this way, the effect of DHT on the transcription of genes responsible for modulation cortexolone 17α preparation of cortexolone 17α within the same family of polymorphs. a further one of known art of cortexolone 17α as in the example 17α as in the example of cortexolone 17α as in the example of cortexolone 17α as in the example cortexolone 17α a) Selective protection of the alcohol group at position 21 of the of formula RCOOR' R' represents a vinyl group of the c) Selective hydrolysis of the ester at position 21 in the presence of lipases in a cortexolone 17α Evaporation of the 17α cortexolone solution an appropriate amount of residual solvent in the art of formula RCOOR', in carbon atoms and R' represents a vinyl group. isolated using techniques well known to the expert in the field and subsequently of the ester in position 21 in the presence that the evaporation of the solution does not occur 'opportune in art cortexolone 17α cortexolone 17α residual solvents. The term “substantially free” indicates residual solvents within the limits Although the invention has been described in its characteristic aspects, modifications and must be seen as limiting the scope of the invention. the resulting oil is solubilized in toluene (500 the desired ester saturated solution (100 mL x 3) up to pH ≥ 8 and with brine (5 (2 g), obtained as reported in E

Claims

CLAIMS 1) Process for the preparation of an amorphous form of cortexolone 17a-propionate of formula (I) comprising the following steps: a) Selective protection of the alcohol group at position 21 of the alcohol of formula (II) 10 in the presence of a vinyl ester of a fatty acid of formula RCOOR' and of a lipase, where: R represents a linear or branched aliphatic chain containing from 10 to 18 carbonium atoms, and R' represents a vinyl group, 15 adcte C is a composite ester of formula (III) CHM045PAT-IT-PRI AL & Partners Srl - 12...... .................... b) Esterification of the ester of formula (III) thus obtained in the presence of aromatic anhydride corresponding to the ester of formula (IV) where R has the meanings covered reported; c) Selective hydrolysis of the ester at position 21 in the presence of a hydrolysis in an organic solvent mixed with water to give cortexolone 17a-decarboxylated 0i formula (1( iasoiaeiune.d) Evaporation of the solution of 17a-deoaiona)o cortexolone of formula (I) obtained until a suitable quantity of residual solvent is reached, and subsequent removal of the solution from one or more organic solvents, e) Removal of any organic solvents to obtain the amorphous form of the compound of formula (I). 2) ProcesscvecnnOv Isrivendicauiono S, innui said fat is chosen between stearic acid and fouric acid, preferably lauric acid. 3) Process eococOv indication P, where PSa lipase used in step a) and in step c) is a resin-supported lipase B from Candida Antarctica. 4) Process excluding any of the preceding processes, wherein said lipase for the uptake a) and in the passage is used in a quantity between 5% and 100% by weight of the substrate. 5) Poozuous) according to any other indications, wherein said vinyl ester Ui of the aceido srasso is used in a quantity πζΙ2)θ comprised between 1 and 20 equivalents, preferably between 1 and 10 equivalents more preferably about 5 equivalents, in relation to the molar quantity of the aceido of formula (II). 6) Processovecondo uea qnaioivsideild η^βι^ϋ^θζίοοί, in which said quantity of solsenPurasiduo nnlzassaggie of is between 0.1 volume and 2volumii paefeslriimsnne oirna 1 volume. 7(Proceedings according to any analysis of the preceding instructions, in which said one or more Ufo 3017)0110^3010 asl psvsagzio d) are indicated in the composition, alcohols selected from CHM045PAT-IT-ORI AL & Partners Srl - 13methanol, ethanol, isopropanol (IPA), n-butanol, t-butanol, 1-butanol, 1-pentanol-, 2-pentanol, ethylene glycol and glycerol; ketones selected from acetone, 3-pentanone, 3-butyl ketone and 4-butyl ketone; Selected esters include ethyl acetate, dipropyl acetate, isopropyl acetate, t-Oxylene acetate, and diisobutyl acetate; selected hydrocarbons, such as methylene dichloride, ethylene dichloride, carbon tetrachloride, and chlorobenzene; aryls such as acetonitrile; dioxane, or their mycelates. 8) Otoceaco according to indication 0| in which one or more organic solvents are ace-oce and metacol. 9) Otoceaco according to unit qi-iots^asi datlerivcedlcczioni a precedi, in which said pressure o) is carried out by distillation, vacuum distillation or spray drying, preferably by spray drying. 10) Otoceal according to procedure 9, in which said epray drying takes place in the presence of a product, mainly ethyl cellulose. tt) Formaamoofe of Clancoteome of formula (I) annetteriezata from an 1-10.