A Convenient Preparation of 4-Carboxamide Derivatives of Pyridazino[4,5-b]indoles and Pyridazino[4,5-b]benzo[b]furans

José C.  González-Gómez; Eugenio  Uriarte

doi:10.1055/s-2002-35569

Subscribe to RSS

Please copy the URL and add it into your RSS Feed Reader.

https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000083.xml

Share / Bookmark

Facebook X Linkedin Weibo

Download PDF

Synlett 2002(12): 2095-2097
DOI: 10.1055/s-2002-35569

LETTER

A Convenient Preparation of 4-Carboxamide Derivatives of Pyridazino[4,5-b]indoles and Pyridazino[4,5-b]benzo[b]furans

José C. González-Gómez*, Eugenio Uriarte
Departamento de Química Orgánica, Facultad de Farmacia, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain
Fax: +34(981)594912; e-Mail: jcgg1971@yahoo.es;

Further Information

Publication History

Received 22 August 2002
Publication Date:
20 November 2002 (online)

Abstract
Full Text
References

Permissions and Reprints All articles of this category

Abstract

Diels-Alder reaction of indole or 3-coumaranone with 3,6-dicarbomethoxy-1,2,4,5-tetrazine followed by MgCl₂-mediated C-4 regioselective amidation of the tricyclic diester and subsequent Krapcho dealkoxycarbonylation, provided a convenient route to 4-carboxamide derivatives of pyridazino[4,5-b]indoles and pyridazino[4,5-b]benzo[b]furans. 1,4-Biscarboxamide derivatives were also obtained by full amidation of diester intermediates with an excess of the amine.

Key words

Diels-Alder reaction - regioselectivity - pyridazine - indoles - benzofurans

References

For recent reviews
1a Braña MR. Cacho M. Gradillas A. De Pascual-Teresa B. Ramos A. Curr. Pharm. Design 2001, 7: 1745

Google Scholar
1b Dalla Via L. Marciani Magno S. Curr. Med. Chem. 2001, 8: 1405

Google Scholar
2a Boger DL. Coleman RS. Panek JS. Yohannes D. J. Org. Chem. 1984, 49: 4405

Google Scholar
2b Boger DL. Panek JS. Patel M. Org. Synth. 1991, 70: 79

Google Scholar
3 González-Gómez JC. Santana L. Uriarte E. Synthesis 2002, 43

Article in Thieme Connect Google Scholar
4a Scitz G. Kampchen T. Arch. Pharm. (Weinheim, Ger.) 1976, 309: 679

Google Scholar
4b González JC. Dedola T. Santana L. Uriarte E. Begala M. Copez D. Podda G. J. Heterocycl. Chem. 2000, 37: 907

Google Scholar
6 For preparation of the trimethylsilyl enol 3 we followed the general procedure described in: Lin J.-M. Liu B.-S. Synth. Commun. 1997, 27: 739

Crossref Google Scholar
7 Jung ME. Abrecht S. J. Org. Chem. 1988, 53: 423

Google Scholar
8a Benson SC. Palabrica CA. Snyder JK. J. Org. Chem. 1987, 52: 4610

Crossref Google Scholar
8b Daly K. Nomak R. Snyder JK. Tetrahedron Lett. 1997, 38: 8611

Crossref Google Scholar
9a Shimizu T. Osako K. Nakata T. Tetrahedron Lett. 1997, 38: 2685

Crossref Google Scholar
9b Akakura M. Yamamoto H. Synlett 1997, 38: 2685

Crossref Google Scholar
9c Patterson JW. J. Org. Chem. 1995, 60: 4542

Crossref Google Scholar
9d Beerli R. Rebek J. Tetrahedron Lett. 1995, 36: 1813

Crossref Google Scholar
9e Schlecker W. Huth A. Ottow E. Mulzer J. Synthesis 1995, 1225

Crossref Google Scholar
9f Sidler DR. Lovelace TC. McNamara JM. Reider PJ. J. Org. Chem. 1994, 59: 1231

Crossref Google Scholar
10 Guo Zh. Dowdy ED. Li W.-S. Polniaszek R. Delaney E. Tetrahedron Lett. 2001, 42: 1843

Crossref Google Scholar
11 The same regioselectivity on the amidation of 7 was observed using the Weinreb protocol: Benson SC. Ph.D. Dissertation Boston University; Boston MA: 1992.

Google Scholar
13 Nomak R. Snyder JK. Tetrahedron Lett. 2001, 42: 7929

Crossref Google Scholar
14a An example of dealkoxycarbonylation on 1,4-diester piridazine systems was previously described refluxing in 1:1 HCl-HOAc: Wan Z.-K. Woo GHC. Snyder JK. Tetrahedron 2001, 57: 5497

Article in Thieme Connect Google Scholar
14b For reviews of dealkoxycarbonylations see: Krapcho AP. Synthesis 1982, 822 ; we are currently working on the optimization of this reaction for the synthesis of related monocarboxamides

Article in Thieme Connect Google Scholar
14c Krapcho AP. Synthesis 1982, 893 ; we are currently working on the optimization of this reaction for the synthesis of related monocarboxamides

Article in Thieme Connect Google Scholar
16 González JC. Lobo-Antunes J. Pérez-Lourido P. Santana L. Uriarte E. Synthesis 2002, 475

Article in Thieme Connect Google Scholar

5

Preparation of 1,4-dicarbomethoxypyridazine[4,5-f]benzo[b]furan(6). Benzofuran-3(2H)-one (7; 142 mg, 1.05 mmol) was added to a dioxane (4 mL) solution of 3,6-dicarbomethoxy-1,2,4,5-tetrazine (190 mg, 0.96 mmol) with a catalytic amount of p-TsOH (10 mg). The reaction mixture was refluxed for 6 h until the red color of the tetrazine had disappeared. The solvent was removed under vacuum and the residue was purified by flash chromatography using 1:2 Hex-EtOAc as eluent, giving pure 6; yield: 200 mg (73%).

12

Amidation of 6 in the absence of MgCl₂ afforded mixtures of monocarboxamides C-4/C-1 in 65/35 for pyrrolidine and
70/30 for N,N-dimethylethylenediamine, as determined by ¹H NMR integration of H-9.

15

Selected physical and spectroscopic data of new compounds. Compound 6: mp 218-220 ºC(dioxane). ¹H NMR (CDCl₃): δ = 8.87 (d, J = 7.95 Hz, 1 H, H-9), 7.82 (m, 2 H), 7.61 (dt, J = 6.60, 1.70 Hz, 1 H), 4.24 (s, 3 H, OCH₃), 4.22 (s, 3 H, OCH₃); ¹³C NMR (CDCl₃): δ = 165.08, 162.57, 157.87, 155.06, 147.87, 140.02, 133.24 (CH), 127.90 (CH), 125.95 (CH), 125.82, 118.48, 113.08 (CH), 54.03 (CH₃), 53.94 (CH₃); MS (EI): m/z (%) = 286 (M⁺, 1.9), 169 (100). Compound 8a: mp 192-194 ºC. ¹H NMR (CDCl₃): δ = 8.89 (d, J = 8.15 Hz, 1 H, H-9), 7.82 (m, 2 H), 7.60 (dt, J = 6.60, 1.70 Hz, 1 H), 4.24 (s, 3 H, OCH₃), 3.88 (t, J = 6.70 Hz, 2 H), 3.74 (t, J = 6.55 Hz, 2 H), 1.96-2.08 (m, 4 H); MS (EI): m/z (%) = 325 (M⁺, 23), 70 (100). Compound 8b: mp 168-171 ºC. ¹H NMR (CDCl₃): δ = 8.89 (d, J = 8.15 Hz, 1 H, H-9), 8.72 (s, 1 H, NH), 7.87 (m, 1 H), 7.82 (m, 1 H), 7.60 (m, 1 H), 4.23 (s, 3 H, OCH₃), 3.68 (t, J = 5.75 Hz, 2 H), 2.62 (t, J = 6.10 Hz, 2 H), 2.33 (s, 6 H). Compound 9a: ¹H NMR (CDCl₃): δ = 11.00 (s, 1 H, NH), 8.84 (d, 1 H, J = 8.25 Hz, H-9), 7.57 (m, 2H, H-6/H-7), 7.37 (m, 1 H, H-8), 4.29 (t, J = 6.50 Hz, 2 H), 4.14 (s, 3 H, OCH₃), 3.77 (t, J = 6.55 Hz, 2 H), 1.95 (m, 4 H); MS (EI): m/z (%) = 324 (M⁺, 15), 168 (100). Compound 9b: ¹H NMR (CDCl₃): δ = 10.83 (s,
1 H, NH), 8.92 (d, J = 8.25 Hz, 1 H, H-9), 8.84 (s, 1 H, NH), 7.70 (m, 2 H), 7.49 (m, 1 H), 4.22 (s, 3 H, OCH₃), 3.69 (m, 2 H), 2.64 (m, 2 H), 2.34 (s, 3 H), 2.33 (s, 3 H). Compound 10a: mp 190-193 ºC. ¹H NMR (CDCl₃): δ = 8.42 (d, J = 7.90 Hz, 1 H, H-9), 7.75 (m, 2 H), 7.55 (m, 1 H), 3.80 (m, 8 H), 2.00 (m, 8 H); MS (EI): m/z (%) = 364 (M⁺, 29), 70 (100). Compound 10b: mp 161-162 ºC. ¹H NMR (CDCl₃): δ = 9.27 (d, J = 8.15 Hz, 1 H, H-9), 8.76 (t, J = 4.80 Hz, 1 H, NH), 8.56 (t, J = 4.80 Hz, 1 H, NH), 7.88 (d, J = 8.45 Hz, 1 H), 7.77 (dt, J = 7.20, 1.35 Hz, 1 H), 7.58 (t, J = 8.18 Hz, 1 H), 3.73 (m, 4 H), 2.63 (m, 4 H), 2.33 (s, 6 H), 2.32 (s, 6 H). Compound 11a: ¹H NMR (CDCl₃): δ = 8.34 (d, J = 8.10 Hz, 1 H, H-9), 7.65 (m, 2 H), 7.40 (m, 1 H), 4.35 (t, J = 6.40 Hz, 2 H), 3.88 (m, 4 H), 3.56 (t, J = 6.50 Hz, 2 H), 2.00 (m, 8 H); MS (EI): m/z (%) = 363 (M⁺, 4), 70 (100). Compound 11b: ¹H NMR (CDCl₃): δ = 10.86 (s, 1 H, NH), 9.35 (d, J = 8.20 Hz, 1 H), 8.73 (m, 2 H, 2NH), 7.65 (m, 2 H), 7.44 (m, 1 H), 3.75 (m, 2 H), 3.68 (m, 2 H), 2.67 (m, 2 H), 2.63 (m, 2 H), 2.35 (s, 6 H), 2.34 (s, 6 H). Compound 12: ¹H NMR (CDCl₃): δ = 9.86 (s, 1 H, H-1), 8.13 (d, J = 7.80 Hz, 1 H, H-9), 7.75 (m, 2 H), 7.56 (m, 1 H), 3.86 (t, J = 6.80 Hz, 2 H), 3.76 (t, J = 6.50 Hz, 2 H), 2.00 (m, 4 H); ¹³C NMR (CDCl₃): δ = 162.29, 156.91, 152.28, 146.09, 145.02, 131.80 (CH), 125.45 (CH), 124.49, 122.66 (CH), 119.56 (CH), 113.67 (CH), 49.11 (CH₂), 46.99 (CH₂), 26.67 (CH₂), 24.56 (CH₂). Compound 13: ¹H NMR (CDCl₃): δ = 10.62 (s, 1 H, NH), 9.76 (s, 1 H, H-1), 8.15 (d, J = 7.95 Hz, 1 H, H-9), 7.57 (m, 2 H), 7.36 (m, 1 H), 4.30 (t, J = 6.40 Hz, 2 H), 3.77 (t, J = 6.50 Hz, 2 H), 1.90 (m, 4 H); ¹³C NMR (CDCl₃): δ = 163.25, 143.07, 140.42, 138.96, 135.26, 128.66 (CH), 121.06 (CH), 120.88, 120.21 (CH), 118.41 (CH), 111.55 (CH), 49.16 (CH₂), 46.98 (CH₂), 25.90 (CH₂), 22.57 (CH₂).