An Efficient Synthesis of New 7-Trifluoromethyl-2,5-disubstituted Pyrazolo[1,5-a]pyrimidines

Abstract

A novel two-step synthesis of trifluoromethylated 3,5-disubstituted pyrazolo[1,5-a]pyrimidines is reported from 3-aminopyrazoles and ethyl 4,4,4-trifluorobut-2-ynoate. The synthetic route begins with the one-pot synthesis of 7-trifluoromethylated pyrazolo[1,5-a]pyrimidin-5-ones by condensation of 3-aminopyrazoles with a fluorinated alkyne. The products obtained are used as building blocks to synthesize directly, with excellent yields via C–O bond activation, a library of new fluorinated 3,5-disubstituted pyrazolo[1,5-a]pyrimidines of biological interest. This operation efficiently allows C–C, C–N and C–S bond formation.

Key words

fluorinated alkynes - 7-trifluoromethylated pyrazolo[1,5-a]pyrimidin-5-ones - C–O bond activation - trifluoromethylated pyrazolo[1,5-a]pyrimidines - biological interest

• References

• 1a Evans BE. Rittle KE. Bock MG. DiPardo RM. Freidinger RM. Whitter WL. Lundell GF. Veber DF. Anderson PS. Chang RS. L. Lotti VJ. Cerino DJ. Chen TB. Kling PJ. Kunkel KA. Springer JP. Hirshfield J. J. Med. Chem. 1988; 31: 2235
• 1b Horton DA. Bourne GT. Smythe ML. Chem. Rev. 2003; 103: 893
• 1c Griffith DA. Hargrove DM. Maurer TS. Blum CA. De Lombaert S. Inthavongsay JK. Klade LE. Mack CM. Rose CR. Sanders MJ. Carpino PA. Bioorg. Med. Chem. Lett. 2011; 21: 2641
• 1d Perdona E. Costantini VJ. Tessari M. Martinelli P. Carignani C. Valerio E. Mok MH. Zonzini L. Visentini F. Gianotti M. Gordon L. Rocheville M. Corsi M. Capelli AM. Neuropharmacology 2011; 61: 957
• 1e Mukaiyama H. Nishimura T. Kobayashi S. Komatsu Y. Kikuchi S. Ozawa T. Kamada N. Ohnota H. Bioorg. Med. Chem. 2008; 16: 909
• 1f Mukaiyama H. Nishimura T. Kobayashi S. Ozawa T. Kamada N. Komatsu Y. Kikuchi S. Oonota H. Kusama H. Bioorg. Med. Chem. 2007; 15: 868
• 1g Tye H. Mueller SG. Prestle J. Scheuerer S. Schindler M. Nosse B. Prevost N. Brown CJ. Heifetz A. Moeller C. Pedret-Dunn A. Whittaker M. Bioorg. Med. Chem. Lett. 2011; 21: 34
• 2a Asano T. Yamazaki H. Kasahara C. Kubota H. Kontani T. Harayama Y. Ohno K. Mizuhara H. Yokomoto M. Misumi K. Kinoshita T. Ohta M. Takeuchi M. J. Med. Chem. 2012; 55: 7772
• 2b Kosugi T. Mitchell DR. Fujino A. Imai M. Kambe M. Kobayashi S. Makino H. Matsueda Y. Oue Y. Komatsu K. Imaizumi K. Sakai Y. Sugiura S. Takenouchi O. Unoki G. Yamakoshi Y. Cunliffe V. Frearson J. Gordon R. Harris CJ. Kalloo-Hosein H. Le J. Patel G. Simpson DJ. Sherborne B. Thomas PS. Suzuki N. Takimoto-Kamimura M. J. Med. Chem. 2012; 55: 6700
• 3 Hwang JY. Windisch MP. Jo S. Kim HC. Kim S. Kim H. Lee ME. Park D.-S. Park E. Ahn S. Cechetto J. Kim J. Liuzzi M. No Z. Lee J. Bioorg. Med. Chem. Lett. 2012; 22: 7297
• 4 Ivashchenko AV. Golovina ES. Kadieva MG. Kysil VM. Mitkin OD. Okun IM. Pharm. Chem. J. 2012; 46: 406
• 5 Xu J. Liu H. Li G. He Y. Ding R. Wang X. Feng M. Zhang S. Chen Y. Li S. Zhao M. Li Y. Qi C. Z. Naturforsch., B 2012; 67: 827
• 6a Kamal A. Tamboli JR. Nayak VL. Adil SF. Vishnuvardhan MV. P. S. Bioorg. Med. Chem. Lett. 2013; 23: 3208
• 6b Williamson DS. Parratt MJ. Bower JF. Moore JD. Richardson CM. Dokurno P. Cansfield AD. Francis GL. Hebdon RJ. Howes R. Jackson PS. Lockie AM. Murray JB. Nunns CL. Powles J. Robertson A. Surgenor AE. Torrance CJ. Bioorg. Med. Chem. Lett. 2005; 15: 863
• 6c Paruch K. Dwyer MP. Alvarez C. Brown C. Chan TY. Doll RJ. Keertikar K. Knutson C. McKittrick B. Rivera J. Rossman R. Tucker G. Fischmann TO. Hruza A. Madison V. Nomeir AA. Wang Y. Lees E. Parry D. Sgambellone N. Seghezzi W. Schultz L. Shanahan F. Wiswell D. Xu X. Zhou Q. James RA. Paradkar VM. Park H. Rokosz LR. Stauffer TM. Guzi TJ. Bioorg. Med. Chem. Lett. 2007; 17: 6220
• 6d Ali S. Heathcote DA. Kroll SH. Jogalekar AS. Scheiper B. Patel H. Brackow J. Siwicka A. Fuchter MJ. Periyasamy M. Tolhurst RS. Kanneganti SK. Snyder JP. Liotta DC. Aboagye EO. Barrett AG. Coombes RC. Cancer Res. 2009; 69: 6208
• 7 Almansa C. de Arriba AF. Cavalcanti FL. Gomez LA. Miralles A. Merlos M. Garcia-Rafanell J. Forn J. J. Med. Chem. 2001; 44: 350
• 8 Bondock S. Fadaly W. Metwally MA. Eur. J. Med. Chem. 2010; 45: 3692
• 9a Selleri S. Bruni F. Costagli C. Costanzo A. Guerrini G. Ciciani G. Gratteri P. Besnard F. Costa B. Montali M. Martini C. Fohlin J. Siena GD. Aiello PM. J. Med. Chem. 2005; 48: 6756
• 9b Chen YL. WO1998008847 A1, 1998 ; JP Patent 2000502723, 2000
• 9c Dusza JP. Albright JD. Tomcufcik AS. US Patent 5538977, 1996
• 10 Dusza JP. Tomcufcik AS. Albright JD. US Patent 4654347, 1987
• 11a Boes M. Stadler H. Riemer C. US Patent 6194410, 2001
• 11b Ramsey SJ. Attkins NJ. Fish R. van der Graaf PH. Br. J. Pharmacol. 2011; 164: 992
• 11c Tellew JE. Lanier M. Moorjani M. Lin E. Luo Z. Slee DH. Zhang X. Hoare SR. Grigoriadis DE. St Denis Y. Di Fabio R. Di Modugno E. Saunders J. Williams JP. Bioorg. Med. Chem. Lett. 2010; 20: 7259
• 11d Wustrow DJ. Capiris T. Rubin R. Knobelsdorf JA. Akunne H. Davis MD. MacKenzie R. Pugsley TA. Zoski KT. Heffner TG. Wise LD. Bioorg. Med. Chem. Lett. 1998; 8: 2067
• 12 O’Donnell PB. Thiele WJ. US Patent 6384221, 2002 ; Chem. Abstr. 2001, 15, 212744f
• 13a Kendall RL. Rubino R. Rutledge R. Bilodeau MT. Fraley ME. Thomas KA. Jr. Hungate RW. US Patent 6235741, 2001 ; Chem. Abstr. 1999, 4, 033028w
• 13b Fraley ME. Hoffman WF. Rubino RS. Hungate RW. Tebben AJ. Rutledge RZ. McFall RC. Huckle WR. Kendall RL. Coll KE. Thomas KA. Bioorg. Med. Chem. Lett. 2002; 12: 2767
• 14a Shen HC. Taggart AK. P. Wilsie LC. Waters MG. Hammond ML. Tata JR. Colletti SL. Bioorg. Med. Chem. Lett. 2008; 18: 4948
• 14b Blad CC. van Veldhoven JP. D. Klopman C. Wolfram DR. Brussee J. Lane JR. IJzerman AP. J. Med. Chem. 2012; 55: 3563
• 15a Gregg BT. Tymoshenko DO. Razzano DA. Johnson MR. J. Comb. Chem. 2007; 9: 507
• 15b Sagar R. Park SB. J. Org. Chem. 2008; 73: 3270
• 16a Dalinger IL. Vatsadse IA. Shevelev SA. Ivachtchenko AV. J. Comb. Chem. 2005; 7: 236
• 16b Drev M. Groselj U. Mevec S. Pusavec E. Strekelj J. Golobic A. Dahmann G. Stanovnik B. Svete J. Tetrahedron 2014; 70: 8267
• 16c Chern JW. Lee CC. Liaw Y.-CW. Andrew HJ. Heterocycles 1992; 34: 1133
• 16d Bruni F. Chimichi S. Cosimelli B. Costanzo A. Guerrini G. Selleri S. Heterocycles 1990; 31: 1141
• 16e Elnagdi MH. Erian AW. Bull. Chem. Soc. Jpn. 1990; 63: 1854
• 16f Hussain SM. El-Reedy AM. El-Sharabasy SA. Tetrahedron 1988; 44: 241
• 16g Ried W. Aboul-Fetouh S. Tetrahedron 1988; 44: 7155
• 16h Stepaniuk OO. Matviienko VO. Kondratov IS. Vitruk IV. Tolmachev AO. Synthesis 2013; 45: 925
• 17a Bajwa JS. Sykes PJ. J. Chem. Soc., Perkin Trans. 1 1979; 3085
• 17b Van Haverbeke Y. Maquestiau A. Van den Eynde JJ. J. Heterocycl. Chem. 1979; 16: 773
• 17c Makisumi Y. Chem. Pharm. Bull. 1962; 10: 620
• 17d Auzzi G. Cecchi L. Costanzo A. Pecori Vettori L. Bruni F. Pirisino R. Ciottoli GB. Farmaco Ed. Sci. 1978; 34: 478
• 17e Compton DR. Sheng S. Carlson KE. Rebacz NA. Lee IY. Katzenellenbogen BS. Katzenellenbogen JA. J. Med. Chem. 2004; 47: 5872
• 17f Gilligan PJ. Baldauf C. Cocuzza A. Chidester D. Zaczek R. Fitzgerald LW. McElroy J. Smith MA. Shen HS. L. Saye JA. Christ D. Trainor G. Robertson DW. Hartig P. Bioorg. Med. Chem. 2000; 8: 181
• 17g Novinson T. Miller JP. Scholten M. Robins RK. Simon LN. O’Brien DE. Meyer RB. Jr. J. Med. Chem. 1975; 18: 460
• 17h Quiroga J. Portilla J. Abonía R. Insuasty B. Nogueras M. Cobo J. Tetrahedron Lett. 2007; 48: 6352
• 17i Abed HB. Mammoliti O. Lommen GV. Herdewijn P. Tetrahedron Lett. 2013; 54: 2612
• 17j Blaney J. Gibbons PA. Hanan E. Lyssikatos JP. Magnuson SR. Pastor R. Rawson TE. Zhou A. Zhu B.-Y. WO2010051549 A1, 2010; US Patent 063014, 2009
• 17k Hölder S. Vennemann M. Beneke G. Zülch A. Gekeler V. Beckers T. Zimmermann A. Joshi H. WO2009021992 A2, 2009 ; EP Patent 060690, 2008
• 17l Emelina EE. Petrov AA. Selivanov SI. Filyukov DV. Russ. J. Org. Chem. 2008; 2: 251
• 17m Al-Afaleq EI. Synth. Commun. 2000; 30: 1985
• 18a Gompper R. Toepfl W. Chem. Ber. 1962; 95: 2861
• 18b Ried W. Peuchert KP. Justus Liebigs Ann. Chem. 1962; 660: 104
• 18c Saikia P. Gogoi S. Boruah RC. J. Org. Chem. 2015; 80: 6885
• 19a Elnagdi MH. Elmoghayar MR. H. Elgemeie GE. H. Adv. Heterocycl. Chem. 1987; 41: 319
• 19b Quiroga J. Hormaza A. Insuasty B. Saitz C. Jullian C. Cannete A. J. Heterocycl. Chem. 1998; 35: 61
• 19c El-Taweel FM. A. Abu Elmaati TM. J. Chin. Chem. Soc. 2002; 49: 1051
• 19d Daniels R. Kim K. Lebois E. Muchalski H. Hughes M. Lindsley C. Tetrahedron Lett. 2008; 49: 305
• 19e Behbehani H. Ibrahim HM. Makhseed S. ARKIVOC 2010; (ii): 267
• 19f Ivachtchenko AV. Golovina ES. Kadieva MG. Kysil VM. Mitkin OD. Tkachenko SE. Okun IM. J. Med. Chem. 2011; 54: 8161
• 19g Ahmetaj S. Velikanje N. Grošelj U. Šterbal I. Prek B. Golobič A. Kočar D. Dahmann G. Stanovnik B. Svete J. Mol. Diversity 2013; 17: 731
• 19h Khalil KD. Al-Matar HM. Al-Dorri DM. Elnagdi MH. Tetrahedron 2009; 65: 9421
• 19i Simon C. Constantieux T. Rodriguez J. Eur. J. Org. Chem. 2004; 4957
• 19j Quiroga J. Mejia D. Insuasty B. Abonia R. Nogueras M. Sanchez A. Cobo J. J. Heterocycl. Chem. 2002; 39: 51
• 20 Zhang X. Song Y. Gao L. Guo X. Fan X. Org. Biomol. Chem. 2014; 12: 2099
• 21 Shekarrao K. Kaishap PP. Saddanapu V. Addlagatta A. Gogoi S. Boruah RC. RSC Adv. 2014; 4: 27001
• 22a Aggarwal R. Masan E. Kaushik P. Kaushik D. Sharma C. Aneja KR. J. Fluorine Chem. 2014; 168: 16
• 22b Yoshida M. Mori A. Inaba A. Oka M. Makino H. Yamaguchi M. Fujita H. Kawamoto T. Goto M. Kimura H. Baba A. Yasuma T. Bioorg. Med. Chem. 2010; 18: 8501
• 22c Emelina EE. Petrov AA. Selivanov SI. Nelyubina YV. Antipin MY. J. Fluorine Chem. 2009; 130: 861
• 22d Shaaban MR. J. Fluorine Chem. 2008; 129: 1156
• 22e Petrov AA. Emelina EE. Selivanov SI. Russ. J. Org. Chem. 2008; 44: 263
• 22f Martins MA. P. Cunico W. Scapin E. Emmerich DJ. Fiss GF. Rosa FA. Bonacorso HG. Zanatta N. Flores AF. C. Lett. Org. Chem. 2006; 3: 358
• 22g Krasovsky AL. Hartulyari AS. Nenajdenko VG. Balenkova ES. Synthesis 2002; 133
• 22h Emelina EE. Petrov AA. Firsov AV. Russ. J. Org. Chem. 2001; 37: 852
• 23a Welch JW. Eswarakrishnan S. In Fluorine in Bioorganic Chemistry . Wiley-Interscience; New York: 1991
• 23b Filler R. Naqui SM. In Biomedical Aspects of Fluorine Chemistry . Elsevier Biomedical; Amsterdam: 1982
• 23c Chemistry of Organic Fluorine Compounds II: A Critical Review, ACS Monograph 187. Hudlický M. Pavlath AE. American Chemical Society; Washington DC: 1995
• 23d Kitazume T. Yamazaki T. Experimental Methods in Organic Fluorine Chemistry . Gordon and Breach Science Publishers; Tokyo: 1998
• 23e Fluorine in Medicinal Chemistry and Chemical Biology. Ojima I. Wiley-Blackwell; Chichester: 2009
• 24a Welch JT. Tetrahedron 1987; 43: 3123
• 24b Selective Fluorination in Organic and Bioorganic Chemistry, ACS Symposium Series 456. Welch JT. American Chemical Society; Washington DC: 1991
• 24c Biomedical Frontiers of Fluorine Chemistry, ACS Symposium Series 639. Ojima I. McCarthy JR. Welch JT. American Chemical Society; Washington DC: 1996
• 24d Purser S. Moore PR. Swallow S. Gouverneur V. Chem. Soc. Rev. 2008; 37: 320
• 24e Hagmann WK. J. Med. Chem. 2008; 51: 4359
• 24f Fustero S. Sanz-Cervera JF. Acena JL. Sanchez-Rosello M. Synlett 2009; 525
• 24g Hunter L. Beilstein J. Org. Chem. 2010; 6: No. 38
• 24h Qing FL. Zheng F. Synlett 2011; 1052
• 24i Gillis EP. Eastman KJ. Hill MD. Donnelly DJ. Meanwell NA. J. Med. Chem. 2015; 58: 8315
• 24j Zhou Y. Wang J. Gu Z. Wang S. Zhu W. Acena JL. Soloshonok VA. Izawa K. Liu H. Chem. Rev. 2016; 116: 422
• 24k Yerien DE. Bonesi S. Postigo A. Org. Biomol. Chem. 2016; 14: 8398 ; and references cited therein
• 25a Petrignet J. Thiery E. Silpa L. Abarbri M. Synthesis 2014; 46: 947
• 25b Silpa L. Petrignet J. Abarbri M. Synlett 2014; 25: 1827
• 25c Silpa L. Niepceron A. Laurent F. Brossier F. Pénichon M. Enguehart-Gueiffier C. Abarbri M. Silvestre A. Petrignet J. Bioorg. Med. Chem. Lett. 2016; 26: 114
• 26a Richard S. Prie G. Guignard A. Thibonnet J. Parrain J.-L. Duchêne A. Abarbri M. Helv. Chim. Acta 2003; 86: 726
• 26b Ella Ndong GJ. Parrain J.-L. Abarbri M. Synthesis 2015; 47: 2635
• 27 Jismy B. Guillaumet G. Allouchi H. Akssira M. Abarbri M. Eur. J. Org. Chem. 2017; 6168
• 28 CCDC 1578767 (pyrazolo[1,5-a]pyrimidin-5-one 3a) contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
• 29a Hauck S. Hiesinger K. Khageh Hosseini S. Achenbach J. Biondi RM. Proschak E. Zörnig M. Odadzic D. Bioorg. Med. Chem. 2016; 24: 5717
• 29b Singh SP. Kapoor JK. Kumar D. Threadgill MD. J. Fluorine Chem. 1997; 83: 73
• 30a Kang FA. Sui Z. Murray WV. J. Am. Chem. Soc. 2008; 130: 11300
• 30b Kang FA. Sui Z. Murray WV. Eur. J. Org. Chem. 2009; 461
• 30c Kang F.-A. Lanter JC. Cai C. Sui Z. Murray WV. Chem. Commun. 2010; 46: 1347
• 30d Shi C. Aldrich CC. Org. Lett. 2010; 12: 2286
• 30e Mehta VP. Modha SG. Van der Eycken E. J. Org. Chem. 2010; 75: 976
• 30f Li S.-M. Huang J. Chena G.-J. Han F.-S. Chem. Commun. 2011; 47: 12840
• 30g Belaroussi R. El Hakmaoui A. Akssira M. Guillaumet G. Routier S. Eur. J. Org. Chem. 2016; 21: 3550
• 31 Miyaura N. Suzuki A. Chem. Rev. 1995; 95: 2457
• 32 Sonogashira K. Tohda Y. Hagihara N. Tetrahedron Lett. 1975; 16: 4467
• 33 Hanan EJ. van Abbema A. Barrett K. Blair WS. Blaney J. Chang C. Eigenbrot C. Flynn S. Gibbons P. Hurley CA. Kenny JR. Kulagowski J. Lee L. Magnuson SR. Morris C. Murray J. Pastor RM. Rawson T. Siu M. Ultsch M. Zhou A. Sampath D. Lyssikatos JP. J. Med. Chem. 2012; 55: 10090
• 34 Saijo R. Watanabe G. Kurihara K.-i. Kawase M. Heterocycles 2014; 89: 2334