Patent SG-11201900125P-A (SG)
Title: Novel processes for preparation of soluble guanylate cyclase stimulators
Inventor: XUE SONG
IPC: C07D413/14
Filed: 2017-07-06
Abstract: INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property MD 1101111 0 11101 010 11111 01 110 1 0 011101 11011101 100 1101 011 MI MI OM Organization International Bureau (10) International Publication Number (43) International Publication Date .....se' WO 2018/009602 A3 11 January 2018 (11.01.2018) W I PO I PCT (51) International Patent Classification: dy; 18 Maybury Road, Sudbury, Massachusetts 01776 CO7D 413/14 (2006.01) A61K 31/53 (2006.01) (US). LIVINGSTON, Robert C.; 63 Stowecroft Road, Ar- C07C 209/00 (2006.01) A61P 9/00 (2006.01) lington, Massachusetts 02474 (US). BARDEN, Timothy C07D 263/34 (2006.01) Claude; 19 Intervale Road, Salem, Massachusetts 01970 (21) International Application Number: (US). SCHAIRER, Wayne C.; 135 Milk Street, Westboro, PCT/US2017/040817 Massachusetts 01581 (US). (22) International Filing Date: (74) Agent: DAVIS, Steven, G.; McCarter & English, LLP, 265 Franklin Street, Boston, Massachusetts 02110 (US). 06 July 2017 (06.07.2017) (25) Filing Language: English (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, (26) Publication Language: English AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, (30) Priority Data: CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, 62/359,430 07 July 2016 (07.07.2016) US 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, (71) Applicant: IRONWOOD PHARMACEUTICALS, INC. KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, [US/US]; 301 Binney Street, Cambridge, Massachusetts MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, 02142 (US). 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, (72) Inventors: XUE, Song; 18 Turner Terrace, Newton, Mass- TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. - achusetts 02460 (US). KARNATI, Vishnu Vardhan Red- = = (54) Title: NOVEL PROCESSES FOR PREPARATION OF SOLUBLE GUANYLATE CYCLASE STIMULATORS = F =R 1 /—R2 HH2N,...„0 = N N ---- CF3 = N _ N N OH = , = ../ Ra 1 10 1 = F = Formula I Compound I = F H 2 N 0 F H2N,-,0 = H -- H N CF F C 3 N \-----\ = „ N 'OH N (S) OH = (R) = — N___ -- 0' _ = .-- 0 0 M Compound IA Compound IB ei © cf•• (57) : The present disclosure relates to novel processes for the preparation of compounds useful as stimulators of soluble C guanylate cyclase (sGC). These processes are amenable to large scale preparation and produce stable 3-(2-pyrimidinyl)pyrazoles of --.... Formula (I), including Compound ( I), Compound (IA) and Compound (IB), in high purity and yields. The present invention has the 0 1-1 0 additional advantage of facile reaction conditions, amenable to scale up for large scale manufacturing. The disclosure also provides C novel intermediates useful in the preparation of said compounds. ei O [Continued on next page] WO 2018/009602 A3 MIDEDIMOMOIDEIRDERIO 011111111011101 11111 11111011111Efin (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, F1, FR, GB, GR, HR, HU, 1E, 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). Published: — with international search report (Art. 21(3)) — before the expiration of the time limit for amending the claims and to be republished in the event of receipt of amendments (Rule 48.2(h)) (88) Date of publication of the international search report: 15 March 2018 (15.03.2018)