Patent SG-11201900096Q-A (SG)
Title: Novel processes for preparation of soluble guanylate cyclase stimulators
Inventor: XUE SONG
IPC: C07D413/04
Filed: 2017-07-06
Abstract: INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property 1111111111111111111111111111111111111111111111111111111111111111111111111110111111 Organization International Bureau (10) International Publication Number (43) International Publication Date .....0\"\" WO 2018/009597 Al 11 January 2018 (11.01.2018) W I PO I PCT (51) International Patent Classification: GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, CO7D 403/04 (2006.01) CO7D 413/04 (2006.01) UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, (21) International Application Number: TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, PCT/US2017/040810 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, (22) International Filing Date: TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, 06 July 2017 (06.07.2017) KM, ML, MR, NE, SN, TD, TG). (25) Filing Language: English Published: (26) Publication Language: English — with international search report (Art. 21(3)) — before the expiration of the time limit for amending the (30) Priority Data: claims and to be republished in the event of receipt of 62/359,453 07 July 2016 (07.07.2016) US amendments (Rule 48.2(h)) (71) Applicant: IRONWOOD PHARMACEUTICALS, INC. [US/US]; 301 Binney Street, Cambridge, Massachusetts 02142 (US). (72) Inventors: XUE, Song; 18 Turner Terrace, Newton, Mass- achusetts 02460 (US). KARNATI, Vishnu Vardhan Red- dy; 18 Maybury Road, Sudbury, Massachusetts 01776 (US). LIVINGSTON, Robert C.; 63 Stowecroft Road, Ar- lington, Massachusetts 02474 (US). — = Agent: DAVIS, Steven G. et al.; McCarter & English, LLP, 265 Franklin Street, Boston, MA 02110 (US). (74) = Designated States (unless otherwise indicated, for every (81) 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. _ Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, — (84) = = = (54) Title: NOVEL PROCESSES FOR PREPARATION OF SOLUBLE GUANYLATE CYCLASE STIMULATORS F = /—R 2 N , r- , - - _ -- 40 O s Il N 1\1 - \"N..—N s Compound (I) .4 (I) N ' N IN CT 1 1 in ---- N OH N H F3C r -----1< C F 3 CT 0 F 0 . E .- 15 (57) : The present disclosure relates to novel processes for the preparation of compounds useful as stimulators of soluble 1-1 guanylate cyclase (sGC). These processes are amenable to large scale preparation and produce stable 3-(2-pyrimidinyl)pyrazoles of 0 el Formula (I), including Compound (I), in high purity and yields. The present invention has the additional advantage of facile reaction conditions, amenable to scale up for large scale manufacturing. The disclosure also provides novel intermediates useful in the preparation 0 of said compounds.