Scalable and Straightforward Synthesis of a 2-Alkyl-7-Arylbenzo­thiophene as a GPR52 Agonist via a Hemithioindigo Derivative

Naohiro Fukuda; Tomomi Ikemoto

doi:10.1055/s-0034-1378746

Synthesis, Inhaltsverzeichnis

Synthesis 2015; 47(22): 3467-3472
DOI: 10.1055/s-0034-1378746

paper

Scalable and Straightforward Synthesis of a 2-Alkyl-7-Arylbenzothiophene as a GPR52 Agonist via a Hemithioindigo Derivative

Naohiro Fukuda*

Chemical Development Laboratories, Takeda Pharmaceutical Company Limited, Yodogawa-ku, Osaka 532-8686, Japan eMail: naohiro.fukuda@takeda.com

,

Tomomi Ikemoto

Chemical Development Laboratories, Takeda Pharmaceutical Company Limited, Yodogawa-ku, Osaka 532-8686, Japan eMail: naohiro.fukuda@takeda.com

› Institutsangaben

Abstract

Alle Artikel dieser Rubrik

Abstract

A simple and efficient procedure has been developed for the synthesis of the GPR52 agonist N-(2-amino-2-oxoethyl)-3-{4-fluoro-2-[3-(trifluoromethyl)benzyl]-1-benzothien-7-yl}benzamide. The benzothiophene unit was directly constructed by reduction of a hemithioindigo derivative prepared by an intramolecular Friedel–Crafts cyclization of (phenylsulfanyl)acetic acid, followed by dehydrative benzylidene formation.

Key words

benzothiophenes - Friedel–Crafts reactions - cyclizations - scalable syntheses - medicinal chemistry

Volltext

Referenzen

References
1 Sawzdargo M, Nguyen T, Lee DK, Lynch KR, Cheng R, Heng HH. Q, George SR, O’Dowd BF. Mol. Brain Res. 1999; 64: 193

2a Setoh M, Ishii N, Kono M, Miyanohana Y, Shiraishi E, Harasawa T, Ota H, Odani T, Kanzaki N, Aoyama K, Hamada T, Kori M. J. Med. Chem. 2014; 57: 5226
2b Komatsu H, Maruyama M, Yao S, Shinohara T, Sakuma K, Imaichi S, Chikatsu T, Kuniyeda K, Sui FK, Peng LS, Zhuo K, Mun LS, Han TM, Matsumoto Y, Hashimoto T, Miyajima N, Ito Y, Ogi K, Habata Y, Mori M. PLoS One 2014; 9: e90134
2c Setoh M, Kobayashi T, Tanaka T, Baba A. WO 2009107391, 2009

3a Horton DA, Bourne GT, Smythe ML. Chem. Rev. 2003; 103: 893
3b Berrade L, Aisa B, Ramirez MJ, Galiano S, Guccione S, Moltzau LR, Levy FO, Nicoletti F, Battaglia G, Molinaro G, Aldana I, Monge A, Perez-Silanes S. J. Med. Chem. 2011; 54: 3086
3c Qin Z, Kastrati I, Chandrasena RE. P, Liu H, Yao P, Petukhov PA, Bolton JL, Thatcher GR. J. J. Med. Chem. 2007; 50: 2682
3d Flynn BL, Hamel E, Jung MK. J. Med. Chem. 2002; 45: 2670
3e Hsiao C.-N, Kolasa T. Tetrahedron Lett. 1992; 33: 2629

4a Fouad I, Mechbal Z, Chane-Ching KI, Adenier A, Maurel F, Aaron J.-J, Vodicka P, Cernovska K, Kozmik V, Svoboda J. J. Mater. Chem. 2004; 14: 1711
4b Jung KH, Kim KH, Lee DH, Jung DS, Park CE, Choi DH. Org. Electron. 2010; 11: 1584
4c Pu S, Li M, Fan C, Liu G, Shen L. J. Mol. Struct. 2009; 919: 100
4d Um M.-C, Kwak J, Hong J.-P, Kang J, Yoon DY, Lee SH, Lee C, Hong J.-I. J. Mater. Chem. 2008; 18: 4698

5a Gabriele B, Mancuso R, Lupinacci E, Veltri L, Salerno G, Carfagna C. J. Org. Chem. 2011; 76: 8277
5b Duan Z, Ranjit S, Liu X. Org. Lett. 2010; 12: 2430
5c Wang Z, Geng W, Wang H, Zhang S, Zhang W.-X, Xi Z. Tetrahedron Lett. 2011; 52: 6997
5d Benati L, Montevecchi PC, Spagnolo P. J. Chem. Soc., Perkin Trans. 1 1992; 1659
5e Hari DP, Hering T, König B. Org. Lett. 2012; 14: 5334
5f Clark PD, Kirk A, Yee JG. K. J. Org. Chem. 1995; 60: 1936
5g Lin C.-H, Chen C.-C, Wu M.-J. Chem. Eur. J. 2013; 19: 2578

6a Capozzi G, Melloni G, Modena G. J. Chem. Soc. C 1970; 2621
6b Jones CD, Jevnikar MG, Pike AJ, Peters MK, Black LJ, Thompson AR, Falcone JF, Clemens JA. J. Med. Chem. 1984; 27: 1057
6c Pinney KG, Bounds AD, Dingeman KM, Mocharla VP, Pettit GR, Bai R, Hamel E. Bioorg. Med. Chem. Lett. 1999; 9: 1081

7a Sun L.-L, Deng C.-L, Tang R.-Y, Zhang X.-G. J. Org. Chem. 2011; 76: 7546
7b Kashiki T, Shinamura S, Kohara M, Miyazaki E, Takimiya K, Ikeda M, Kuwabara H. Org. Lett. 2009; 11: 2473

8a Ebata H, Miyazaki E, Yamamoto T, Takimiya K. Org. Lett. 2007; 9: 4499
8b Zhou Y, Liu W.-J, Ma Y, Wang H, Qi L, Cao Y, Wang J, Pei J. J. Am. Chem. Soc. 2007; 129: 12386
8c Hessian KO, Flynn BL. Org. Lett. 2003; 5: 4377
8d Larock RC, Yue D. Tetrahedron Lett. 2001; 42: 6011
8e Flynn BL, Verdier-Pinard P, Hamel E. Org. Lett. 2001; 5: 651

9a Kuhn M, Falk FC, Paradies J. Org. Lett. 2011; 13: 4100
9b Lyons TW, Sanford MS. Chem. Rev. 2010; 110: 1147
9c Bryan CS, Braunger JA, Lautens M. Angew. Chem. Int. Ed. 2009; 48: 7064

10a Yu H, Zhang M, Li Y. J. Org. Chem. 2013; 78: 8898
10b Newman SG, Aureggi V, Bryan CS, Lautens M. Chem. Commun. 2009; 5236
10c Lu W.-D, Wu M.-J. Tetrahedron 2007; 63: 356
10d Kunz T, Knochel P. Angew. Chem. Int. Ed. 2012; 51: 1958

11 Liu K, Jia F, Xi H, Li Y, Zheng X, Guo Q, Shen B, Li Z. Org. Lett. 2013; 15: 2026
12 Nakamura I, Sato T, Yamamoto Y. Angew. Chem. Int. Ed. 2006; 45: 4473
13 Godoi B, Schumacher RF, Zeni G. Chem. Rev. 2011; 111: 2937
14 Inamoto K, Arai Y, Hiroya K, Doi T. Chem. Commun. 2008; 5529

15a Duez S, Steib AK, Knochel P. Org. Lett. 2012; 14: 1951
15b Shrestha S, Hwang SY, Lee K.-H, Cho H. Bull. Korean Chem. Soc. 2005; 26: 1138
15c Lapointe D, Fagnou K. Org. Lett. 2009; 11: 4160
15d Imamura M, Nakanishi K, Suzuki T, Ikegai K, Shiraki R, Ogiyama T, Murakami T, Kurosaki E, Noda A, Kobayashi Y, Yokota M, Koide T, Kosakai K, Ohkura Y, Takeuchi M, Tomiyama H, Ohta M. Bioorg. Med. Chem. 2012; 20: 3263
15e Robbins DW, Hartwig JF. Angew. Chem. Int. Ed. 2013; 52: 933

16a Anderson NG. Practical Process Research and Development: A Guide for Organic Chemists . 2nd ed. Elsevier Academic Press; Amsterdam: 2012
16b Repič O. Principles of Process Research and Chemical Development in the Pharmaceutical Industry. Wiley; New York: 1998

17 Varedian M, Langer V, Bergquist J, Gogoll A. Tetrahedron Lett. 2008; 49: 6033
18 Kurosawa K, Morita Y. Bull. Chem. Soc. Jpn. 1981; 54: 635

19a Burger U, Bringhen AO. Helv. Chim. Acta 1989; 72: 93
19b Sainsbury M, Webb B, Schinazi R. J. Chem. Soc., Perkin Trans. 1 1975; 289

20 The selectivity was determined by ¹H NMR. Ethyl [(2-Bromo-5-fluorophenyl)sulfanyl]acetate (12) ¹H NMR (600 MHz, CDCl₃): δ = 1.27 (t, J = 7.2 Hz, 3 H), 3.68 (s, 2 H), 4.21 (q, J = 7.2 Hz, 2 H), 6.79 (t, J = 8.3 Hz, 1 H), 7.09 (dd, J = 9.3, 2.8 Hz, 1 H), 7.49 (t, J = 7.5 Hz, 1 H); ¹³C NMR (151 MHz, CDCl₃): δ = 14.1, 35.4, 61.9, 114.4 (d, J = 22.3 Hz), 115.6 (d, J = 25.6 Hz), 117.4 (d, J = 3.3 Hz), 134.0 (d, J = 8.2 Hz), 139.0 (d, J = 8.2 Hz), 162.1 (d, J = 249.0 Hz), 168.6. Ethyl [(4-Bromo-3-fluorophenyl)sulfanyl]acetate (Regioisomer of 12) ¹H NMR (600 MHz, CDCl₃): δ = 1.25 (t, J = 7.1 Hz, 3 H), 3.64 (s, 2 H), 4.19 (q, J = 7.3 Hz, 2 H), 7.05 (ddd, J = 8.4, 2.2, 0.8 Hz, 1 H), 7.17 (dd, J = 9.0, 2.1 Hz, 1 H), 7.46 (dd, J = 8.2, 7.3 Hz, 1 H); ¹³C NMR (151 MHz, CDCl₃): δ = 14.1, 36.3, 61.8, 107.3 (d, J = 21.3 Hz), 117.3 (d, J = 24.5 Hz), 126.1 (d, J = 3.3 Hz), 133.7, 136.9 (d, J = 7.1 Hz), 159.0 (d, J = 250.1 Hz), 169.1.
21 Eggers K, Fyles TM, Montoya-Pelaez PJ. J. Org. Chem. 2001; 66: 2966

22a Fukuda N, Kajiwara T, Katou T, Majima K, Ikemoto T. Synlett 2013; 24: 1438
22b Fukuda N, Izumi M, Ikemoto T. Tetrahedron Lett. 2015; 56: 3905

23 Zhang TY. Handbook of Green Chemistry and Technology . Clark J, Macquarrie D. Blackwell Science; Oxford: 2002: 312
24 Rueping M, Vila C, Szadkowska A, Koenigs RM, Fronert J. ACS Catal. 2012; 2: 2810

Zusatzmaterial

Supporting Information

Scalable and Straightforward Synthesis of a 2-Alkyl-7-Arylbenzo­thiophene as a GPR52 Agonist via a Hemithioindigo Derivative

Scalable and Straightforward Synthesis of a 2-Alkyl-7-Arylbenzothiophene as a GPR52 Agonist via a Hemithioindigo Derivative