Synlett 2017; 28(19): 2660-2664
DOI: 10.1055/s-0036-1588517
letter
© Georg Thieme Verlag Stuttgart · New York

Chemoselective Synthesis of N-(Aminoalkyl/amidino)phenyl Naphthalene-1-carboxamides and 5,6,7,8-Tetrahydronaphthalene-1-carboxamides and Their Anticoagulant Screening

Thi Ha Nguyena, b, Eunsook Ma*a
  • aCollege of Pharmacy, Catholic University of Daegu, Hayang-ro 13-13, Hayang-eup, Gyeongsan-si, Gyeongbuk 712-702, Republic of Korea   Email: masook@cu.ac.kr
  • bDepartment of Phytochemistry, National Institute of Medicinal Materials (NIMM), Hanoi 100000, Vietnam
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science, and Technology (2010-0013516)
Further Information

Publication History

Received: 13 May 2017

Accepted after revision: 03 July 2017

Publication Date:
08 August 2017 (eFirst)

Abstract

N-[(Aminoalkyl)phenyl]-1-naphthamides and N-[(amino­alkyl)phenyl]-5,6,7,8-tetrahydronaphthalene-1-carboxamides were selectively synthesized from the corresponding cyanonaphthamides by catalytic hydrogenation. N-(Amidinophenyl)-1-naphthalenecarbox­amides and N-(amidinophenyl)-5,6,7,8-tetrahydronaphthalene-1-carboxamides were chemoselectively obtained from the corresponding O-acetylamidoximes or amidoximes, respectively, by catalytic hydrogenation. The products were screened for their anticoagulant effects in human plasma, as measured by the activated partial thromboplastin time and the prothrombin time in vitro. Amidines and 5,6,7,8-tetra­hydronaphthamides were more active than aminoalkyl compounds and naphthamides.

Supporting Information

 
  • References and Notes

    • 1a Hirsh J. Dalen J. Anderson DR. Poller L. Bussey H. Ansell J. Deykin D. Chest 2001; 119: 8S
    • 1b Wells PS. Holbrook AM. Crowther NR. Hirsh J. Ann. Intern. Med. 1994; 121: 676
  • 2 Linkins L.-A. Weitz JI. Annu. Rev. Med. 2005; 56: 63
    • 3a Furugohri T. Isobe K. Honda Y. Kamisato-Matsumoto C. Sugiyama N. Nagahara T. Morishima Y. Shibano T. J. Thromb. Haemostasis 2008; 6: 1542
    • 3b Ishihara T. Koga Y. Mori K. Sugasawa K. Iwatsuki Y. Hirayama F. Bioorg. Med. Chem. 2014; 22: 6324
  • 4 Pinto DJ. P. Smallheer JM. Cheney DL. Knabb RM. Wexler RR. J. Med. Chem. 2010; 53: 6243
  • 5 Pasumansky L. Goralski CT. Singaram B. Org. Process Res. Dev. 2006; 10: 959
  • 6 Khurana JM. Kukreja G. Synth. Commun. 2002; 32: 1265
  • 7 Saavedra JZ. Resendez A. Rovira A. Eagon S. Haddenham D. Singaram B. J. Org. Chem. 2012; 77: 221
  • 8 Prasad AS. B. Kanth JV. B. Periasamy M. Tetrahedron 1992; 48: 4623
  • 9 Bagal DM. Bhanage BM. Adv. Synth. Catal. 2015; 357: 883
  • 10 Granik VG. Russ. Chem. Rev. 1983; 52: 377
  • 11 Aly AA. Nour-El-Din AM. ARKIVOC 2008; (i): 153
    • 12a Roger R. Neilson DG. Chem. Rev. 1961; 61: 179
    • 12b Schaefer FC. Peters GA. J. Org. Chem. 1961; 26: 412
    • 12c Schaefer FC. Krapcho AP. J. Org. Chem. 1962; 27: 1255
  • 13 Garigipati RS. Tetrahedron Lett. 1990; 31: 1969
  • 14 Mahajan US. Godinde RR. Mandhare PN. Synth. Commun. 2011; 41: 2195
  • 15 Nadrah K. Dolenc SM. Synlett 2007; 1257
  • 16 Brian DJ. Allen DG. Cook TA. Evans B. Sardharwala TE. Synth. Commun. 1996; 26: 4351
  • 17 Kim TH. Gu SK. Bae JS. J. Cell. Biochem. 2012; 113: 2877
  • 18 N-[(Aminoalkyl)phenyl]-2-ethoxynaphthalene-1-carboxamide Hydrochlorides 4–6; General Procedure 10% Pd/C (12 mg) and concd HCl (6.93 mg, 0.19 mmol) were added to a solution of the appropriate nitrile 13 (0.19 mmol) in absolute EtOH (15 mL), and the mixture was hydrogenated (40 psi) at r.t. for 3 h. The mixture was filtered through a Celite pad that was washed with cold EtOH. The filtrate was evaporated under reduced pressure to give a beige solid that was crystallized from EtOH–Et2O to give pure white or pale-yellow crystals. N-[3-(Aminomethyl)phenyl]-2-ethoxy-1-naphthamide Hydrochloride (4) White solid; yield: 31 mg (51%); mp 88–89 °C. 1H NMR (400 MHz, DMSO-d 6): δ = 10.57 (s, 1 H, NH), 8.25 (br s, 3 H, NH2·HCl), 8.03 (d, J = 9.2 Hz, 1 H, H-8), 8.00 (s, 1 H, H-2′), 7.93 (d, J = 8.4 Hz, 1 H, H-5), 7.69 (d, J = 8.4 Hz, 1 H, H-4), 7.63 (d, J = 8.0 Hz, 1 H, H-6′), 7.47–7.55 (m, 2 H, H-3,7), 7.35–7.44 (m, 2 H, H-6,5′), 7.26 (d, J = 7.2 Hz, 1 H, H-4′), 4.24 ( q, J = 6.8 Hz, 2 H, OCH2), 3.96 (s, 2 H, CH2) 1.29 (t, J = 6.8 Hz, 3 H, CH3). 13C NMR (100 MHz, DMSO-d 6): δ = 165.5 (C=O), 152.6 (C-2), 139.7 (C-3′), 136.0 (C-1′), 131.0 (C-4), 130.9 (C-5′), 130.6 (C-7), 129.1 (C-8a), 128.2 (C-5), 128.1 (C-4a), 127.3 (C-6), 124.0 (C-4′), 123.8 (C-3), 123.6 (C-8), 122.0 (C-6′), 119.2 (C-2′), 115.4 (C-1), 64.8 (OCH2), 42.6 (CH2), 15.0 (CH3). DIP-MS (EI): m/z = 320 [M – HCl]+. HRMS (FAB): m/z [M + H]+ calcd for C20H20N2O2: 321.1603; found: 321.1621.