Transformations of 3-Amino-N-[2-(5-methyl-2-furyl)ethyl]thieno[2,3-b]pyridine-2-carboxamides in Acidic Media

Tatyana A. Stroganova; Vladimir K. Vasilin; Gennady D. Krapivin

doi:10.1055/s-0035-1561400

Synlett, Table of Contents

Synlett 2016; 27(10): 1569-1571
DOI: 10.1055/s-0035-1561400

letter

Transformations of 3-Amino-N-[2-(5-methyl-2-furyl)ethyl]thieno[2,3-b]pyridine-2-carboxamides in Acidic Media

Tatyana A. Stroganova*

^aDepartment of Bioorganic Chemistry and Technical Microbiology, Kuban State Technological University, Moskovskaya st. 2, Krasnodar 350072, Russian Federation Email: tatka_s@mail.ru

,

Vladimir K. Vasilin

^aDepartment of Bioorganic Chemistry and Technical Microbiology, Kuban State Technological University, Moskovskaya st. 2, Krasnodar 350072, Russian Federation Email: tatka_s@mail.ru

,

Gennady D. Krapivin

^bResearch Institute of Heterocyclic Compounds Chemistry, Kuban State Technological University, Moskovskaya st. 2, Krasnodar 350072, Russian Federation

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Abstract

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Abstract

Acid-catalyzed transformations of N-(5-methyl-2-furyl)ethyl 3-aminothieno[2,3-b]pyridine-2-carboxamides accompanied with furan ring opening were investigated. Based on furan ring recyclization several derivatives of the new fused heterocyclic system – pyrrolo[1,2-a][1,4]diazocine – were obtained. The structures of the synthesized compounds were assigned by their NMR, IR, and MS data.

Key words

furans - ring opening - vicinal aminoamides - cyclization - pyrrolo[1,2-a]diazocines

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References

References and Notes
1 Wong HN. C, Yeung K.-S, Yang Z In Comprehensive Heterocyclic Chemistry III. Katritzky AR. Elsevier; Oxford: 2008

2a Padwa A, Flick AC In Advances in Heterocyclic Chemistry. Vol. 110; Katritzky AR. Academic Press, Elsevier; New York: 2013: 1
2b Gulbrandsen HS, Hennum M, Osheka M, Read ML, Gundersen L.-L. Eur. J. Org. Chem. 2014; 36: 8182
2c Zubkov FI, Nikitina EV, Galeev TR, Zaytsev VP, Khrustalev VN, Novikov RA, Orlova DN, Varlamov AV. Tetrahedron 2014; 70: 1659

3 Merino P. Org. React. 2015; 87: 1
4 Lee H.-K, Chan K.-F, Hui Ch.-W, Yim H.-K, Wu X.-W, Wong HN. C. Pure Appl. Chem. 2005; 77: 139
5 Wong HN. C, Yu P, Yick CY. Pure Appl. Chem. 1999; 71: 1041
6 Stroganova T, Vasilin V, Butin A, Nevolina T, Krapivin G. Synlett 2007; 1106

7a Satishkumar S, Periasamy M. Tetrahedron: Asymmetry 2009; 20: 2257
7b Valik M, Cejka J, Havlik M, Kral V, Dolensky B. Chem. Commun. 2007; 3835
7c Kim E.-I, Paliwal S, Wilcox CS. J. Am. Chem. Soc. 1998; 120: 11192
7d Crossley MJ, Mackay LG, Try AC. J. Chem. Soc., Chem. Commun. 1995; 1925
7e Weber E, Müller U, Worsch D, Vögtle F, Will G, Kirfel A. J. Chem. Soc., Chem. Commun. 1985; 1578

8a Veale EB, Frimannsson DO, Lawler M, Gunnlaugsson T. Org. Lett. 2009; 11: 4040
8b Tatibouёt A, Demeunynck M, Andraud C, Collet A, Lhomme J. Chem. Commun. 1999; 161

9 Wilcox CS, Cowart MD. Tetrahedron Lett. 1986; 27: 5563

10a Weilandt T, Kiehne U, Schnakenburg G, Lützen A. Chem. Commun. 2009; 2320
10b Khoshbin MS, Ovchinnikov MV, Mirkin CA, Golen JA, Rheingold AL. Inorg. Chem. 2006; 45: 2603

11 Kiehne U, Bruhn T, Schnakenburg G, Fröhlich R, Bringmann G, Lützen A. Chem. Eur. J. 2008; 14: 4246
12 Galaso V, Jones D, Modelli A. Chem. Phys. 2003; 33–42: 288

13a Sergeyev S. Helv. Chim. Acta 2009; 92: 415
13b Dolensky B, Elguero J, Kral V, Pardo C, Valik M. Adv. Heterocycl. Chem. 2007; 93: 1
13c Demeunynck M, Tatibouёt A. Prog. Heterocycl. Chem. 1999; 11: 1
13d Pardo C, Alkorta I, Elguero J. Tetrahedron: Asymmetry 2006; 17: 191
13e Aamouche A, Devlin FJ, Stephens PJ. J. Am. Chem. Soc. 2000; 122: 2346
13f Wilen SH, Qi JZ, Williard PG. J. Org. Chem. 1991; 56: 485

14a Corres N, Delgado JJ, Garćia-Valverde M, Marcaccini S, Rodriguez T, Rojo J, Torroba T. Tetrahedron 2008; 64: 2225
14b Fuwa H, Okamura Y, Morohashi Y, Tomita T, Iwatsubo T, Kan T, Fukuyama T, Natsugari H. Tetrahedron Lett. 2004; 45: 2323

15 Synthesis of 3-Amino-N-[2-(5-methyl-2-furyl)ethyl]thieno-[2,3-b]pyridine-2-carboxamides 1a–c – General Procedure To a mixture of the corresponding pyridine-2-thione 2a–c (2 mmol) and aq KOH (10%, 11.2 mL, 2 mmol) in DMF (20 mL) N-(5-methylfuryl-2)ethyl chloroacetamide (3, 2 mmol) was added, and the resulted mixture was stirred for 30–40 min at r.t. Then a second portion of aq KOH (11.2 mL, 2 mmol) was added, and the resultant mixture was magnetically stirred for 0.5–1 h until precipitate formation. The crystals were filtered off, washed with cold aq EtOH and dried to yield 3-amino-N-[2-(5-methyl-2-furyl)ethyl]thieno[2,3-b]pyridine-2-carboxamides 1a–c in 60–72% yield. 3-Amino-4,6-dimethyl-N-[2-(5-methyl-2-furyl)ethyl]thieno-[2,3-b]pyridine-2-carboxamide (1a) Yield 68%; pale yellow crystals; mp 136–138 °C. IR (ATR): 3429 (NH₂), 3386 (NH₂), 3256 (NH), 1621 (C=O) cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 2.19 (3 H, s, 5′′-CH₃), 2.46 (3 H, s, 6-CH₃), 2.68 (3 H, s, 4-CH₃), 2.72 (2 H, t, ³J = 7.4 Hz, 2′-CH₂), 3.48 (2 H, dt, ³J = 7.6, 5.7 Hz, 1′-CH₂), 5.91 (1 H, d, ³J = 3.0 Hz, 4′′-H), 5.99 (1 H, d, ³J = 3.0 Hz, 3′′-H), 6.75 (2 H, s, NH₂), 6.94 (1 H, s, 5-H), 7.75 (1 H, t, ³ J = 5.7 Hz, CONH). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 13.7 (C-5′′-CH₃), 20.2 (C-4-CH₃), 24.2 (C-6-CH₃), 28.5 (C-2′), 38.4 (C-1′), 97.9 (C-2), 106.7 (C-4′′), 106.8 (C-3′′), 122.2 (C-5), 123.6 (C-3a), 144.8 (C-4), 148.1 (C-3), 150.4 (C-5′′), 151.9 (C-2′′), 158.8 (C-6), 158.9 (C-7a), 165.8 (C=O). MS (EI, 70 eV): m/z (%) = 330 (8) [M + 1], 329 (33) [M]⁺, 222 (18), 206 (11), 205 (100), 204 (46), 177 (8), 133 (7), 43 (16). Anal. Calcd for C₁₇H₁₉N₃O₂S: C, 61.98; H, 5.81; N, 12.76. Found: C, 62.05; H, 5.74; N, 12.86.
16 General Procedure for the Reaction of Aminoamides 1a–c in HCl–AcOH – Method A A mixture of aminoamide 1 (2 mmol), AcOH (10 mL), and concd HCl (1.5 mL) was stirred at r.t. until no initial compound remained (monitoring by TLC). Then the mixture was poured into cold H₂O (100 mL), neutralized with NaHCO₃ to pH 6–7, and extracted with EtOAc (3 × 15 mL). The extracts were dried (Na₂SO₄), filtered, evaporated in vacuo to dryness, and the residue purified by column chromatography. The eluent was selected individually for each case. 3-Amino-N-[3,6-dioxoheptyl-4,6-dimethylthieno[2,3-b]pyridine-2-carboxamide (4a) Yield 67%; white powder; mp 133–135 °C. IR (ATR): 3433 (NH₂), 3313 (NH₂), 3225 (NH), 1710 (C=O), 1602 (NHC=O) cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 2.08 (3 H, s, 7′-CH₃), 2.46 (3 H, s, 6-CH₃), 2.62 (4 H, s, 4′-CH₂ + 5′-CH₂), 2.68 (3 H, s, 4-CH₃), 2.70 (2 H, t, ³J = 7.1 Hz, 2′-CH₂), 3.39 (2 H, dt, ³J = 7.1, 5.6 Hz, 1′-CH₂), 6.75 (2 H, s, NH₂), 6.99 (1 H, s, 5-H), 7.50 (1 H, t, ³ J = 5.6 Hz, CONH). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 20.2 (C-4-CH₃), 24.2 (C-6-CH₃), 30.0 (C-7′), 34.9 (C-1′), 36.3 (C-4′), 37.0 (C-5′), 42.4 (C-3′), 97.8 (C-2), 122.2 (C-5), 123.6 (C-3a), 144.9 (C-4), 148.1 (C-3), 158.9 (C-7a), 159.0 (C-6), 165.8 (C=O), 207.7 (C-6′-C=O), 208.6 (C-3′-C=O). MS (EI, 70 eV): m/z (%) = 348 (5) [M + 1], 347 (29) [M]⁺, 221 (21), 205 (100), 204 (24), 178 (19), 144 (6), 99 (15), 77 (8), 43 (28). Anal. Calcd for C₁₇H₂₁N₃O₃S: C, 58.77; H, 6.09; N, 12.09. Found: C, 58.89; H, 6.00; N, 12.19. 2,4,5a-Trimethyl-5,5a,6,7,9,10-hexahydropyrido[3′′,2′′:4′,5′]-thieno[3′,2′:4,5]pyrimido[1,2-a]azepine-8,12-dione (5) Yield 8%; white powder; mp 277–278 °C. IR (ATR): 3350 (NH), 1708 (C=O), 1603 (NHC=O) cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 1.49 (3 H, s, 5a-CH₃), 2.26–2.40 (2 H, m, 6-CH₂), 2.36 (1 H, ddd, ² J = 15.2 Hz, ³ J = 3.5, 10.1 Hz, 7-He), 2.39–2.46 (2 H, m, 9-CH₂), 2.48 (3 H, s, 2-CH₃), 2.66 (3 H, s, 4-CH₃), 3.03 (1 H, ddd, ² J = 15.2 Hz, ³ J = 10.1, 3.5 Hz, 7-Ha), 3.25 (1 H, ddd, ² J = 14.2 Hz, ³ J = 3.5, 6.0 Hz, 10-CHe), 4.31 (1 H, ddd, ² J = 14.2 Hz, ³ J = 6.0 Hz, ³ J = 10.0 Hz, 10-CHa), 6.13 (1 H, s, NH), 7.03 (1 H, s, 3-H). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 20.0 (C-4-CH₃), 23.3 (C-5a-CH₃), 24.3 (C-2-CH₃), 33.3 (C-6), 33.4 (C-10), 39.0 (C-7), 44.1 (C-9), 76.6 (C-5a), 103.6 (C-12a), 121.9 (C-3), 122.8 (C-4a), 144.1 (C-4b), 145.0 (C-4), 158.9 (C-2), 160.2 (C-12-C=O), 161.9 (C-13a), 209.8 (C-8-C=O). MS (EI, 70 eV): m/z (%) = 330 (8) [M + 1], 329 (41) [M]⁺, 314 (27), 273 (10), 247 (11), 205 (17), 204 (100), 149 (17), 129 (8), 105 (10), 90 (7), 54 (17), 43 (22). Anal. Calcd for C₁₇H₁₉N₃O₂S: C, 61.98; H, 5.81; N, 12.76. Found: C, 62.11; H, 5.84; N, 12.66.
17 General Procedure for the Reaction of Aminoamides 1a–c with HCl–AcOH – Method B A mixture of amide 1 (2 mmol), AcOH (10 mL), and concd HCl (1.5 mL) was heated at 55–60 °C with stirring until no initial amide or intermediate diketone 4 remained (monitoring by TLC). Then the mixture was poured into cold H₂O (100 mL), neutralized with NaHCO₃ to pH 6–7, and extracted with EtOAc (3 × 15 mL). The extracts were dried (Na₂SO₄), filtered, evaporated in vacuo to dryness, and the residue purified by column chromatography. The eluent was selected individually for each case. 1,10,12-Trimethyl-5,6-dihydropyrido[3′,2′:4,5]thieno[2,3-g]pyrrolo[1,2-a][1,5]diazocin-7(4H)-one (6a) Yield 56%; white powder; mp 294–296 °C. IR (ATR): 3391 (NH), 1641 (C=O) cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.75 (3 H, s, 12-CH₃), 2.01 (3 H, s, 1-CH₃), 2.23 (1 H, ddd, ² J = 16.2 Hz, ³ J = 8.5, 2.3 Hz, 4-Ha), 2.38 (1 H, ddd, ² J = 16.2 Hz, ³ J = 11.6, 3.5 Hz, 4-He), 2.63 (3 H, s, 10-CH₃), 3.20 (1 H, dddd, ² J = 12.0 Hz, ³ J = 9.0, 3.5, 8.5 Hz, 5-Ha), 4.22 (1 H, dddd,, ² J = 12.0 Hz, ³ J = 2.3, 11.6, 2.3 Hz, 5-He), 5.74 (1 H, d,³ J = 3.5 Hz, 3-H), 5.96 (1 H, dd, ³ J = 9.0, 2.3 Hz NH-5-CH₂), 6.11 (1 H, d,³ J = 3.5 Hz, 2-H), 6.93 (1 H, s, 11-H). ¹³C NMR (100 MHz, CDCl₃): δ = 12.2 (C-1-CH₃), 16.4 (C-12-CH₃), 24.4 (C-10-CH₃), 27.5 (C-4), 35.3 (C-5), 107.6 (C-3), 109.4 (C-2), 123.1 (C-11), 127.0 (C-12a), 127.1 (C-7a), 128.8 (C-3a), 129.5 (C-1), 135.2 (C-12b), 143.6 (C-12), 158.9 (C-10), 159.7 (C-8a), 160.2 (C=O). MS (EI, 70 eV): m/z (%) = 312 (24) [M + 1], 311 (100) [M]⁺, 269 (12), 267 (33), 255 (8), 215 (6), 43 (25). Anal. Calcd for C₁₇H₁₇N₃OS: C, 65.57; H, 5.50; N, 13.49. Found: C, 65.73; H, 5.59; N, 13.54.

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