Synthesis of 2-(2-Dialkylamino-4H-3,1-benzothiazin-4-yl)acetic Acid Derivatives
and 2-(2-Thioxo-1,2,3,4-tetrahydroquinazolin-4-yl)acetic Acid Derivatives

Shuhei Fukamachi; Hisatoshi Konishi; Kazuhiro Kobayashi

doi:10.1055/s-0029-1218746

PAPER

Synthesis of 2-(2-Dialkylamino-4H-3,1-benzothiazin-4-yl)acetic Acid Derivatives and 2-(2-Thioxo-1,2,3,4-tetrahydroquinazolin-4-yl)acetic Acid Derivatives

Shuhei Fukamachi, Hisatoshi Konishi, Kazuhiro Kobayashi*
Division of Applied Chemistry, Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University, 4-101 Koyama-minami, Tottori 680-8552, Japan
Fax: +81(857)315263; e-Mail: kkoba@chem.tottori-u.ac.jp;

Abstract

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Abstract

An efficient method for the preparation of 2-(4H-3,1-benzothiazin-4-yl)acetic acid derivatives and 2-(2-thioxo-1,2,3,4-tetrahydroquinazolin-4-yl)acetic acid derivatives has been developed. The reaction of 3-(2-isothiocyanatophenyl)propenoic acid derivatives with secondary amines in methanol at room temperature gave the corresponding thiourea intermediates, which on heating at reflux temperature cyclized by an attack of the sulfur atom on the propenoic moiety in a 1,4-addition manner, to give 2-(2-dialkylamino-4H-3,1-benzothiazin-4-yl)acetic acid derivatives in one pot. A similar sequence using primary amines in place of secondary amines afforded 2-[3-alkyl(or aryl)-2-thioxo-1,2,3,4-tetrahydroquinazolin-4-yl]acetic acid derivatives.

Key words

4H-3,1-benzothiazines - 2-thioxo-1,2,3,4-tetrahydroquinazolines - 3-(2-isothiocyanatophenyl)propenoic acids - thioureas - 1,4-addition

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References

1a Schilling S, Cynis H, Hoffmann T, and Demuth H.-U. inventors; US Pat. Appl. US 068699. ; Chem. Abstr. 2009, 150, 322579

1b Anzini M, Giordani A, Makovec F, Cappelli A, Vomero S, Caselli G, Rovati G, and Lucio C. inventors; PCT Int. Pat. Appl. 040331. ; Chem. Abstr. 2009, 150, 374522

1c Reynisson J. Court W. O’Neill C. Day J. Patterson L. McDonald E. Workman P. Katan M. Eccles SA. Bioorg. Med. Chem. 2009, 17: 3169

1d Anthes JC, McCormick KD, Hey JA, Aslanian RG, Biju PJ, Berlin MY, Solomon DM, Wang DM, Wang H, Lim Y.-H, Lee YJ, and Bitar R. D. inventors; PCT Int. Pat. Appl. WO 085879. ; Chem. Abstr. 2009, 151, 124232

1e Nielsen M, Liljefors T, Nilsson J, and Sterner O. inventors; PCT Int. Pat. Appl. WO 123536. ; Chem. Abstr. 2009, 151, 425736

2a Beilenson B. Hamer FM. J. Chem. Soc. 1942, 98

2b Besson T. Guillaumet G. Lamazzi C. Rees CW. Thiery V. J. Chem. Soc., Perkin Trans. 1 1998, 4057

2c El-Desoky SI. Kandeel EM. Abd-el-Rahman AH. Schmidt RR. J. Heterocycl. Chem. 1999, 36: 153

2d Hari A. Miller BL. Org. Lett. 2000, 2: 3667

2e Femandes MA. Reid DA. Synlett 2003, 2231

3 After completion of our work, we became aware of a report by Gimbert and Vallribera, which describe a synthesis of 2-[2-alkyl(or aryl)-4H-3,1-benzothiazin-4-yl]acetic acid derivatives by the reaction of 3-(2-acylamino-phenyl)propenoic acid derivatives with Lawesson’s reagent in refluxing toluene: Gimbert C. Vallribera A. Org. Lett. 2009, 11: 269

4a Hasegawa H. Muraoka M. Ohmori M. Matsui K. Kojima A. Bioorg. Med. Chem. 2005, 13: 3721

4b Sarli V. Huemmer S. Sunder-Plassmann N. Mayer TU. Giannis A. ChemBioChem 2005, 6: 2005

4c Peters J.-U. Luebbers T. Alanine A. Kolczewski S. Blasco F. Steward L. Bioorg. Med. Chem. Lett. 2008, 18: 256

4d Peters J.-U. Luebbers T. Alanine A. Kolczewski S. Blasco F. Steward L. Bioorg. Med. Chem. Lett. 2008, 18: 262

5a Pflegel P. Kuehmstedt C. Richter P. Pharmazie 1981, 36: 65

5b Richter P. Oertel F. Pharmazie 1990, 45: 721

5c Pfeiffer WD. Pazdera P. Hetzheim A. Muecke J. Pharmazie 1995, 50: 21

6 Fujiwara S. Shin-Ike T. Sonoda N. Aoki M. Okada K. Miyoshi N. Kambe N. Tetrahedron Lett. 1991, 32: 3503

7 Xiao W.-J. Alper H. J. Org. Chem. 1999, 64: 9646

8 Hays SJ. Caprathe BW. Gilmore JL. Amin N. Emmerling MR. Michael W. Nadimpalli R. Nath R. Raser KJ. Stafford D. Watson D. Wang K. Jaen JC. J. Med. Chem. 1998, 41: 1060

9 Kobayashi K. Yoneda K. Miyamoto K. Morikawa O. Konishi H. Tetrahedron 2004, 60: 11639

10 Ziegler CB. Heck RF. J. Org. Chem. 1978, 43: 2941

11 Tokuyama H. Kaburagi Y. Chen X. Fukuyama T. Synthesis 2000, 429

12 Ito Y. Kobayashi K. Seko N. Saegusa T. Bull. Chem. Soc. Jpn. 1984, 54: 73