Synlett 2014; 25(19): 2797-2801
DOI: 10.1055/s-0034-1379100
letter
© Georg Thieme Verlag Stuttgart · New York

Multipathways for the Synthesis of Fused Bicyclic 2-Aminothiazolyl Compounds Tuned by Ring Size

Pengfei Liu
a   Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, P. R. of China   Fax: +86(21)64252603   Email: xyxu@ecust.edu.cn
,
Hongfeng Shen
a   Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, P. R. of China   Fax: +86(21)64252603   Email: xyxu@ecust.edu.cn
,
Xusheng Shao
a   Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, P. R. of China   Fax: +86(21)64252603   Email: xyxu@ecust.edu.cn
,
Zhong Li
a   Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, P. R. of China   Fax: +86(21)64252603   Email: xyxu@ecust.edu.cn
b   Shanghai Collaborative Innovation Center for Biomanufacturing Technology, 130 Meilong Road, Shanghai 200237, P. R. of China
,
Xiaoyong Xu*
a   Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, P. R. of China   Fax: +86(21)64252603   Email: xyxu@ecust.edu.cn
b   Shanghai Collaborative Innovation Center for Biomanufacturing Technology, 130 Meilong Road, Shanghai 200237, P. R. of China
› Author Affiliations
Further Information

Publication History

Received: 20 June 2014

Accepted after revision: 18 August 2014

Publication Date:
16 October 2014 (online)


Abstract

A new methodology for the synthesis of fused bicyclic 2-aminothiazolyl compounds has been developed, using cyclo­condensation of aromatic thioureas with α,β-epoxy cycloketones in alcohol under microwave irradiation without any catalyst. The product distribution is related to the ring size of α,β-epoxy cyclo­ketones. Mechanistic studies suggest that the reactions share analogous bicyclic dihydroxy intermediates but undergo different further reactions to give diverse products.

Supporting Information

 
  • References and Notes

    • 1a Gorczynski MJ, Leal RM, Mooberry SL, Bushweller JH, Brown ML. Bioorg. Med. Chem. 2004; 12: 1029
    • 1b Wang W.-L, Yao D.-Y, Gu M, Fan M.-Z, Li J.-Y, Xing Y.-C, Nan F.-J. Bioorg. Med. Chem. Lett. 2005; 15: 5284
    • 1c Di Francesco ME, Dessole G, Nizi E, Pace P, Koch U, Fiore F, Pesci S, Di Muzio J, Monteagudo E, Rowley M, Summa V. J. Med. Chem. 2009; 52: 7014
    • 1d Llinàs-Brunet M, Bailey MD, Goudreau N, Bhardwaj PK, Bordeleau J, Bös M, Bousquet Y, Cordingley MG, Duan J, Forgione P, Garneau M, Ghiro E, Gorys V, Goulet S, Halmos T, Kawai SH, Naud J, Poupart M.-A, White PW. J. Med. Chem. 2010; 53: 6466
  • 2 Griss G, Schneider C, Hurnaus R, Kobinger W, Pichler L, Bauer R, Mierau J, Hinzen D, Schingnitz G. EPO 186087, 1986 ; Chem. Abstr. 1987, 106, 5015.
  • 3 Prasanna DS, Kavitha CV, Vinaya K, Ranganatha SR, Raghava B, Kumar YC. S, Raghavan SC, Rangappa KS. B. Chem. Soc. Jpn. 2010; 83: 689
  • 4 Moyes CR, Berger R, Goble SD, Harper B, Shen D.-M, Wang L, Bansal A, Brown PN, Chen AS, Dingley KH, Di Salvo J, Fitzmaurice A, Gichuru LN, Hurley AL, Jochnowitz N, Miller RR, Mistry S, Nagabukuro H, Salituro GM, Sanfiz A, Stevenson AS, Villa K, Zamlynny B, Struthers M, Weber AE, Edmondson SD. J. Med. Chem. 2014; 57: 1437
  • 5 Pinacho Crisóstomo FR, Feng Y, Zhu X, Welsh K, An J, Reed JC, Huang Z. Bioorg. Med. Chem. Lett. 2009; 19: 6413
    • 6a Barchéchath SD, Tawatao RI, Corr M, Carson DA, Cottam HB. J. Med. Chem. 2005; 48: 6409
    • 6b Lv P.-C, Zhou C.-F, Chen J, Liu P.-G, Wang K.-R, Mao W.-J, Li H.-Q, Yang Y, Xiong J, Zhu H.-L. Bioorg. Med. Chem. 2010; 18: 314
  • 7 Ritchie TJ, Macdonald SJ. F, Young RJ, Pickett SD. Drug Discov. Today 2011; 16: 164
    • 8a Zhang W, Yue Y, Yu D, Song L, Xu YY, Tian YJ, Guo YJ. Adv. Synth. Catal. 2012; 354: 2283
    • 8b Wang R, Yang W.-j, Yue L, Pan W, Zeng H.-y. Synlett 2012; 23: 1643
    • 8c Yang J, Li P, Wang L. Tetrahedron 2011; 67: 5543
    • 8d Wang R, Chen Z, Yue L, Pan W, Zhao J.-J. Tetrahedron Lett. 2012; 53: 4529
    • 8e Shen G, Lv X, Bao W. Eur. J. Org. Chem. 2009; 5897
    • 8f Rout SK, Guin S, Nath J, Patel BK. Green Chem. 2012; 14: 2491
    • 8g Cano R, Ramón DJ, Yus M. J. Org. Chem. 2010; 76: 654
    • 8h Saha P, Ramana T, Purkait N, Ali MA, Paul R, Punniyamurthy T. J. Org. Chem. 2009; 74: 8719
    • 8i McGowan MA, Henderson JL, Buchwald SL. Org. Lett. 2012; 14: 1432
    • 8j Ma D, Lu X, Shi L, Zhang H, Jiang Y, Liu X. Angew. Chem. Int. Ed. 2011; 50: 1118
    • 8k Zhao J, Huang H, Wu W, Chen H, Jiang H. Org. Lett. 2013; 15: 2604
    • 8l Mitamura T, Iwata K, Ogawa A. J. Org. Chem. 2011; 76: 3880
    • 8m Gao H, Ess DH, Yousufuddin M, Kürti LS. J. Am. Chem. Soc. 2013; 135: 7086
    • 8n Esmaili R, Nematollahi D. J. Org. Chem. 2013; 78: 5018
    • 9a Hantzsch A, Weber JH. Ber. Dtsch. Chem. Ges. 1887; 20: 3118
    • 9b Shen S.-S, Lei M.-Y, Wong Y.-X, Tong M.-L, Teo PL.-Y, Chiba S, Narasaka K. Tetrahedron Lett. 2009; 50: 3161
    • 9c Guernon JM, Wu Y.-J. Tetrahedron Lett. 2011; 52: 3633
    • 9d Lübbers T, Flohr A, Jolidon S, David-Pierson P, Jacobsen H, Ozmen L, Baumann K. Bioorg. Med. Chem. Lett. 2011; 21: 6554
    • 9e Schwarz O, Jakupovic S, Ambrosi H.-D, Haustedt LO, Mang C, Müller-Kuhrt L. J. Comb. Chem. 2007; 9: 1104
    • 9f Alam M, Khan S, Shaheen Khan M. J. Chil. Chem. Soc. 2008; 53: 1714
    • 9g Hong S.-P, Liu KG, Ma G, Sabio M, Uberti MA, Bacolod MD, Peterson J, Zou ZZ, Robichaud AJ, Doller DO. J. Med. Chem. 2011; 54: 5070
    • 9h John OR, Killeen NM, Knowles DA, Yau SC, Bagley MC, Tomkinson NC. Org. Lett. 2007; 9: 4009
  • 10 Yadav JS, Reddy BV. S, Rao YG, Narsaiah AV. Tetrahedron Lett. 2008; 49: 2381
  • 11 Gasteiger J, Herzig C. Tetrahedron 1981; 37: 2607
  • 12 Ohler E. Monatsh. Chem. 1993; 124: 763
  • 13 Bicyclic dihydroxy intermediates for the seven-membered ring were not obtained due to the low reaction activities of benzothioamide and α,β-epoxycyclopentanone.
    • 14a Kasturi T, Chandra R. J. Org. Chem. 1988; 53: 3178
    • 14b Kasturi TR, Chandra R, Reddy SM, Venkatesan K, Srikrishnan T, Row TN. G, Puranik VG, Tavale SS. J. Chem. Soc., Chem. Commun. 1987; 75
  • 15 Schmittel M, Steffen J.-P, Auer D, Maywald M. Tetrahedron Lett. 1997; 38: 6177
  • 16 General Procedure for the Preparation of Fused Bicyclic 2-Aminothiazolyl Compounds To a microwave vial (2–5 mL) were added aryl thiourea 1 (1 mmol), α,β-epoxy cycloketone 2 (1.05 mmol), and the corresponding alcohol (2 mL). The sealed vial was heated in the Biotage Initiator Synthesizer for an appropriate time. The mixture was then cooled to r.t., and the residue was obtained after evaporating under vacuum. The residue was subjected to purification over silica gel chromatography eluting with PE–EtOAc (9:1, v/v) to afford target compounds. N-(4-Chlorophenyl)-7-methoxy-4,5,6,7-tetrahydrobenzo[d]thiazol-2-amine (3a) White solid; yield: 273 mg (93%); mp 113.5–114.2 °C. 1H NMR (400 MHz, DMSO-d 6): δ =10.25 (s, 1 H), 7.65 (d, J = 8.6 Hz, 2 H), 7.34 (d, J = 8.6 Hz, 2 H), 4.37 (t, J = 4.2 Hz, 1 H), 3.33 (s, 3 H), 2.62–2.48 (m, 2 H), 1.89–1.78 (m, 4 H). 13C NMR (100 MHz, DMSO-d 6): δ = 162.4, 148.8, 140.5, 129.2, 124.8, 118.7, 118.5, 72.6, 55.9, 28.7, 27.1, 19.3. ESI-HRMS: m/z [M + H]+ calcd for C14H16 35ClN2OS+: 295.0672; found: 295.0674; calcd for C14H16 37ClN2OS+: 297.0642; found: 297.0642. 2-[(4-Chlorophenyl)amino]-4,5-dihydro-3aH-cyclopenta[d]thiazol-6(6aH)-one (4a) White solid; yield: 226 mg (85%); mp 147.0–148.2 °C. 1H NMR (400 MHz, CDCl3): δ = 7.26 (d, J = 8.8 Hz, 2 H), 7.12 (d, J = 8.8 Hz, 2 H), 6.68 (s, 1 H), 4.89–4.84 (m, 1 H), 3.96 (d, J = 7.2 Hz, 1 H), 2.64–2.52 (m, 1 H), 2.43–2.32 (m, 1 H), 2.32–2.17 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ = 214.0, 159.4, 143.7, 129.2, 129.0, 122.2, 66.6, 54.1, 34.4, 27.9. ESI-HRMS: m/z [M + H]+ calcd for C12H12 35ClN2OS+: 267.0359; found: 267.0366; calcd for C12H12 37ClN2OS+: 269.0329; found: 269.0335. N-(4-Chlorophenyl)-5,6-dihydro-4H-cyclohepta[d]thiazol-2-amine (5a) Light yellow solid; yield: 190 mg (69%); mp 126.5–128.0 °C.1H NMR (400 MHz, DMSO-d 6): δ = 10.21 (s, 1 H), 7.62 (d, J = 8.8 Hz, 2 H), 7.33 (d, J = 8.8 Hz, 2 H), 6.17 (d, J = 11.6 Hz, 1 H), 5.77–5.70 (m, 1 H), 2.92 (t, J = 5.6 Hz, 2 H), 2.41–2.36 (m, 2 H), 1.85 (dt, J = 11.2, 5.6 Hz, 2 H). 13C NMR (100 MHz, DMSO-d 6): δ = 160.2, 150.6, 140.5, 129.4, 129.2, 124.8, 118.7, 118.3, 118.0, 33.5, 30.6, 22.9. ESI-HRMS: m/z [M + H]+ calcd for C14H14 35ClN2S+: 277.0566; found: 236.0568; calcd for C14H14 37ClN2S+: 279.0537; found: 279.0542.