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Synlett 2016; 27(10): 1569-1571
DOI: 10.1055/s-0035-1561400
letter
© Georg Thieme Verlag Stuttgart · New York

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

Tatyana A. Stroganova*
a   Department 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
a   Department 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
b   Research Institute of Heterocyclic Compounds Chemistry, Kuban State Technological University, Moskovskaya st. 2, Krasnodar 350072, Russian Federation
› Institutsangaben
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Publikationsverlauf

Received: 10. Januar 2016

Accepted after revision: 05. Februar 2016

Publikationsdatum:
07. März 2016 (online)

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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

Supporting Information

    Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0035-1561400.
  • Supporting Information
 

  • References and Notes

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  • 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.