Patent SG-11201811291Q-A (SG)
Title: Industrial process for the preparation of cariprazine
Inventor: Neu József 
IPC: C07D295/06
Filed: 2017-07-07
Abstract: INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date 11 January 2018 (11.01.2018) W I PO I PCT omit n OH iolo III 11111111 El ME 10111110 011 (10) International Publication Number WO 2018/007986 Al C07D 295/06 (2006.01) C07C 275/26 (2006.01) Declarations under Rule 4.17: as to applicant's entitlement to apply for and be granted a (21) International Application Number: patent (Rule 4.17 (ii)) PCT/1B2017/054094 of inventorship (Rule 4.17(iv)) (22) International Filing Date: Published: 07 July 2017 (07.07.2017) with international search report (Art. 21(3)) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: P1600420 08 July 2016 (08.07.2016) HU P1700197 09 May 2017 (09.05.2017) HU (71) Applicant: RICHTER GEDEON NYRT. [HU/HU]; Gyomroi fit 19-21., H-1103 Budapest (HU). (72) Inventors: NEU, Jozsef; Hegedus Gyula u. 44/B., H-1133 Budapest (HU). GARADNAY, Sandor; Langliliom u. 3/ B., 1037 Budapest (HU). SZABO, Minas; Hunyadi fit 112., 5830 Battonya (HU). (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). 1-1 (54) Title: INDUSTRIAL PROCESS FOR THE PREPARATION OF CARIPRAZINE (57) : I n the process of the present invention, cariprazine is prepared by converting (trans-4-amino- cyclohexyl)-acetic acid ethyl ester hydrochloride to trans-4-aminocyclohexyl) acetic acid or its hydrochloride by hydrolysis, from the obtained product with N addition of dimethylcarbamoyl derivative as a suitable reagent (trans-4- {[(dimethylamino)carbonyl]aminol cyclohexyl) acetic acid is formed, then the obtained compound is linked to 1-{2,3-dichloropheny1)—piperazine in the presence of carboxylic acid activating cou- pling reagent, and so 1,1-dimethy1-3-[trans-4-(2- oxo-2-(4-(2,3-dichlorophenyl)piperazin-l-yl-ethyl)cyclohexyl] urea is formed, which c)1: 1-1 is converted to cariprazine borane adduct of formula (2) in the presence of reducing agent, and fmally the product itself is eliminated directly or is obtained from its salt by a known method. The invention also relates to a group of intermediate compounds that are formed ei and/or used in the process according to the present invention. (51) International Patent Classification: