SG11201901983PA - Process for preparation of 2-(6-nitropyridin-3-yl)-9h-dipyrido[2,3-b;3',4'-d]pyrrole - Google Patents

Abstract

INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property 111111101111 0 1110101011111 011101 0 0111111111111111111111111111111111111110111111 Organization International Bureau (10) International Publication Number (43) International Publication Date .....0\"\" WO 2018/046428 Al 15 March 2018 (15.03.2018) WI P0 I P C T (51) International Patent Classification: strasse 124, 4070 Basel (CH). MURI, Dieter; c/o F. Hoff- C07D 471/04 (2006.01) mann-La Roche AG, Grenzacherstrasse 124, 4070 Basel (21) International Application Number: (CH). PCT/EP2017/072062 (74) Agent: POPPE, Regina; Grenzacherstrasse 124, 4070 (22) International Filing Date: Basel (CH). 04 September 2017 (04.09.2017) (81) Designated States (unless otherwise indicated, for every (25) Filing Language: English kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, (26) Publication Language: English CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, (30) Priority Data: DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, 16187960.6 09 September 2016 (09.09.2016) EP 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, (71) Applicant (for all designated States except US): F. HOFF- MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, MANN-LA ROCHE AG [CH/CH]; Grenzacherstrasse OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, 124, 4070 Basel (CH). 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. (71) Applicant (for US only): HOFFMANN-LA ROCHE INC. [US/US]; Overlook at Great Notch, 150 Clove Road, (84) Designated States (unless otherwise indicated, for every _ 8th Floor, Suite 8 - Legal Department, Little Falls, New Jer- kind of regional protection available): ARIPO (BW, GH, sey 07424 (US). GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, — (72) Inventors: BARTELS, Bjoern; c/o F. Hoffmann-La Roche AG, Grenzacherstrasse 124, 4070 Basel (CH). TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, Fk FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, _ — CUENI, Philipp; c/o F. Hoffmann-La Roche AG, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, Grenzacherstrasse 124, 4070 Basel (CH). KOERNER, Matthias; c/o F. Hoffmann-La Roche AG, Grenzacher- = _ = _ Title: PROCESS FOR PREPARATION OF 2-(6-NITROPYRIDIN-3-YL)-9H-DIPYRIDO[2,3-B;3',4'-D]PYRROLE = (54) = = (57) : The present invention relates to a process for preparation of the compound — of formula (I) which processes comprise: a) coupling a compound of formula (2), wherein a / \ — = — 1 p leaving group 0-502-R is selected from the triflate group, the tosylate group, the mesylate ,,, N - / N ' - group, the besylate group, the nosylate group or the brosylate group, with a suitable boronic o I acid, a trifluoroborate or a boronic acid ester under argon condition and in the presence of a = = catalyst and a base in a suitable solvent and then isolating the product as an acid addition salt to afford the compound of formula (Ia) and b) converting the acid addition salt of formula (Ia) wherein the acid HX comprises suitable organic or inorganic acids into the compound of = — \ formula (I) by treatment with at least a stoichiometric equivalent of a suitable base. = N N O' S°2-R = H 2, = = = / \ o N N. N N 0 11 x HX Ia GC ei ii- \ . ____ 0 ,-.... N N N+ N H 0 I 11 ei C [Continued on next page] WO 2018/046428 Al O II TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). Declarations under Rule 4.17: — of inventorship (Rule 4.17(iv)) Published: — with international search report (Art. 21(3))