Synthesis of 2-Alkylidene-3-acylquinoxalines from N-Aryl-2-nitrosoanilines and 1,3-Diketones

Abstract

In the reaction of N-aryl-2-nitrosoanilines with β-diketones, a condensation of the nitroso group with diketone carbanion followed by condensation of the amino function with the less crowded carbonyl group leads to 2-alkylidene-3-acyl-1,2-dihydroquinoxalines under mild basic conditions.

Key words

cyclization - condensation - heterocycles - annulation - ring closure

• References and Notes

• 1a Wróbel Z, Kwast A. Synlett 2007; 1525
• 1b Wróbel Z, Kwast A. Synthesis 2010; 3865
• 2a Wróbel Z, Stachowska K, Grudzień K, Kwast A. Synlett 2011; 1439
• 2b Bujok R, Cmoch P, Wróbel Z. Tetrahedron Lett. 2014; 55: 3410
• 2c Łukasik E, Wróbel Z. Synlett 2014; 25: 217
• 3 Kwast A, Stachowska K, Trawczyński A, Wróbel Z. Tetrahedron Lett. 2011; 52: 6484
• 4a Wróbel Z, Stachowska K, Kwast A, Gościk A, Królikiewicz M, Pawłowski R, Turska I. Helv. Chim. Acta 2013; 96: 956
• 4b Królikiewicz M, Cmoch P, Wróbel Z. Synlett 2013; 24: 973
• 4c Wróbel Z, Królikiewicz M. J. Heterocycl. Chem. 2014; 51: 123
• 4d Królikiewicz M, Błaziak K, Danikiewicz W, Wróbel Z. Synlett 2013; 24: 1945

For a review of recent advances in the synthesis of quinoxalines and medicinal compounds containing a quinoxaline moiety, see:
• 5a Mamedov VA, Zhukova NA. Prog. Heterocycl. Chem. 2012; 24: 55
• 5b Eary CT, Jones ZS, Groneberg RD, Burgess LE, Mareska DA, Drew MD, Blake JF, Laird ER, Balachari D, O’Sullivan M, Allen A, Marsh V. Bioorg. Med. Chem. Lett. 2007; 17: 2608
• 5c Ohtake Y, Naito A, Hasegawa H, Kawano K, Morizono D, Taniguchi M, Tanaka Y, Matsukawa H, Naito K, Oguma T, Ezure Y, Tsuriya Y. Bioorg. Med. Chem. 1999; 7: 1247
• 5d Torisu K, Kobayashi K, Iwahashi M, Nakai Y, Onoda T, Sugimoto I, Okada Y, Matsumoto R, Nanbu F, Ohuchida S, Nakai H, Toda M. Bioorg. Med. Chem. 2004; 12: 5361
• 5e Sikorski JA. J. Med. Chem. 2006; 49: 1
• 5f Jacobsen EJ, Stelzer LS, Belonga KL, Carter DB, Im WB, Sethy VH, Tang AH, VonVoigtlander PF, Petke JD. J. Med. Chem. 1996; 39: 3820
• 5g Barrows TH, Farina PR, Chrzanowski RL, Benkovic PA, Benkovic SJ. J. Am. Chem. Soc. 1976; 98: 3678
• 6 General Procedure for the Synthesis of Compounds 3 To a solution of N-aryl-2-nitrosobenzamine (0.5 mmol) and an appropriate 1,3-diketone (0.6 mmol) in dry DMF (5 mL) was added DBU (1 mmol). The mixture was stirred at r.t. for 24 h. The mixture was then poured into sat. NH₄Cl solution and extracted with EtOAc, the combined extract was washed with H₂O, dried (Na₂SO₄), and concentrated. The products were isolated by column chromatography (SiO₂; hexane–toluene, 1:1).
• 7 Analytical Data for New Compounds 1 and 3 Compound 1g: dark green solid; mp 90–92 °C. ¹H NMR (400 MHz, CDCl₃): δ = 1.20 (t, J = 7.6 Hz, 3 H), 2.57 (q, J = 7.6 Hz, 2 H), 6.81 (d, J = 2.0 Hz, 1 H), 6.92–6.95 (m, 1 H), 7.22–7.32 (m, 3 H), 7.33–7.37 (m, 1 H), 8.69 (br s, 1 H), 12.00 (br s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 14.7, 24.7, 114.6, 118.6, 126.8, 127.2, 128.0, 130.0, 134.3, 140.1, 144.8, 155.3 (two C missing). ESI-MS (MeOH): m/z = 261 [M + H]⁺, 283 [M + Na]⁺. ESI-HRMS (MeOH): m/z calcd for C₁₄H₁₃N₂ONaCl: 283.0614; found: 283.0604. Compound 1h: dark green solid; mp 69–71 °C. ¹H NMR (400 MHz, CDCl₃): δ = 1.37 (s, 9 H), 6.71–6.76 (m, 1 H), 6.90–6.93 (m, 1 H), 7.16–7.19 (m, 1 H), 7.21–7.33 (m, 2 H), 7.50–7.54 (m, 1 H), 8.70 (br s, 1 H), 12.26 (br s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 14.7, 24.7, 114.6, 118.6, 126.8, 127.2, 128.0, 130.0, 134.3, 140.1, 144.8, 155.3 (two C missing). ESI-MS (MeOH): m/z = 289 [M + H]⁺, 311 [M + Na]⁺, 599 [2 M + Na]⁺. ESI-HRMS (MeOH): m/z calcd for C₁₆H₁₇N₂ONaCl: 311.0927; found: 311.0923. Compound 3aa: yellow solid; mp 157–159 °C. ¹H NMR (500 MHz, CDCl₃): δ = 2.17 (s, 6 H), 3.52 (br s, 1 H), 3.98 (br s, 1 H), 5.98 (d, J = 1.7 Hz, 1 H), 6.83 (dd, J = 8.3, 1.9 Hz, 1 H), 7.25–7.30 (m, 3 H), 7.49–7.53 (m, 2 H), 7.34 (d, J = 8.3 Hz, 1 H), 7.62–7.66 (m, 1 H), 8.06–8.10 (m, 2 H). ¹³C NMR (125 MHz, CDCl₃): δ = 17.7, 88.5, 111.3, 120.8, 128.8, 129.4, 130.0, 130.1, 130.4, 131.1, 134.1, 134.4, 134.5, 135.6, 136.4, 136.6, 159.5, 192.1 (one C missing). MS (EI): m/z (%) = 388 (44), 386 (100) [M⁺], 373 (20), 372 (15), 371 (56), 359 (19), 358 (17), 357 (51), 283 (28), 282 (18), 281 (84), 267 (12), 266 (26), 265 (17), 105 (49), 77 (44). HRMS (EI): m/z calcd for C₂₄H₁₉N₂OCl: 386.1186; found: 386.1192. Compound 3ab: dark red solid; mp 66–68 °C. ¹H NMR (500 MHz, CDCl₃): δ = 2.10 (s, 6 H), 2.60 (s, 3 H), 3.55 (d, J = 1.5 Hz, 1 H), 4.84 (d, J = 1.5 Hz, 1 H), 5.84 (d, J = 1.9 Hz, 1 H), 6.77 (dd, J = 8.3, 1.9 Hz, 1 H), 7.23–7.29 (m, 3 H), 7.31 (d, J = 8.3 Hz, 1 H). ¹³C NMR (125 MHz, CDCl₃): δ = 17.7, 27.7, 88.9, 111.2, 120.5, 129.2, 130.0, 130.7, 131.0, 134.0, 134.4, 136.5, 136.6, 137.6, 155.2, 199.2. MS (EI): m/z (%) = 326 (27), 324 (67) [M⁺], 311 (30), 310 (18), 309 (88), 283 (33), 282 (21), 281 (100), 268 (13), 267 (23), 266 (32), 265 (15), 252 (10), 77 (11), 44 (22). HRMS (EI): m/z calcd for C₁₉H₁₇N₂OCl: 324.1029; found: 324.1028. Compound 3ba: orange solid; mp 202–204 °C (dec.). ¹H NMR (500 MHz, CDCl₃): δ = 2.21 (s, 6 H), 3.50 (d, J = 2.2 Hz, 1 H), 3.97 (d, J = 2.2 Hz, 1 H), 6.20 (d, J = 1.5 Hz, 1 H), 7.09 (dd, J = 8.0, 1.5 Hz, 1 H), 7.24–7.31 (m, 4 H), 7.32–7.38 (m, 4 H), 7.47–7.54 (m, 3 H), 7.61–7.65 (m, 1 H), 8.12 (m, 2 H). ¹³C NMR (125 MHz, CDCl₃): δ = 17.8, 87.4, 109.8, 119.7, 127.0, 127.7, 128.7, 128.8, 129.1, 129.7, 129.9, 130.1, 131.9, 134.2, 134.6, 134.8, 134.9, 136.3, 136.8, 140.4, 143.7, 159.3, 192.4. MS (EI): m/z (%) = 428 (83) [M⁺], 414 (18), 413 (57), 400 (23), 399 (57), 324 (26), 323 (100), 308 (27), 307 (20), 297 (10), 214 (11), 105 (43), 77 (36). HRMS (EI): m/z calcd for C₃₀H₂₄N₂O: 428.1889; found: 428.1886. Compound 3bb: dark red solid; mp 82–85 °C. ¹H NMR (400 MHz, CDCl₃): δ = 2.14 (s, 6 H), 2.63 (s, 3 H), 3.53 (d, J = 1.6 Hz, 1 H), 4.83 (d, J = 1.6 Hz, 1 H), 6.07 (d, J = 2.0 Hz, 1 H), 7.05 (dd, J = 8.0, 2.0 Hz, 1 H), 7.22–7.26 (m, 4 H), 7.33–7.36 (m, 4 H), 7.46 (d, J = 8.0 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 17.9, 27.9, 87.9, 109.8, 119.6, 127.1, 128.0, 128.8, 129.1, 130.0, 130.5, 131.7, 134.8, 135.0, 136.0, 136.9, 140.5, 144.9, 155.1, 199.6. MS (EI): m/z (%) = 366 (72) [M⁺], 352 (30), 351 (83), 324 (40), 323 (100), 321 (11), 309 (26), 308 (37), 307(27), 294 (15), 43 (12). HRMS (EI): m/z calcd for C₂₅H₂₂N₂O: 366.1732; found: 366.1736. Compound 3bc: red solid; mp 151–154 °C. ¹H NMR (400 MHz, CDCl₃): δ = 1.23 (d, J = 7.2 Hz, 6 H), 2.14 (s, 6 H), 3.48 (d, J = 2.0 Hz, 1 H), 3.70 (sept, J = 7.2 Hz, 1 H), 4.42 (d, J = 2.0 Hz, 1 H), 6.10 (d, J = 1.6 Hz, 1 H), 7.06 (dd, J = 8.0, 1.6 Hz, 1 H), 7.22–7.27 (m, 4 H), 7.32–7.34 (m, 4 H), 7.45 (d, J = 8.0 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 17.8, 17.9, 37.4, 87.3, 109.8, 119.6, 127.1, 127.9, 128.4, 129.1, 130.0, 130.1, 131.8, 135.1, 135.5, 135.6, 136.9, 140.5, 144.3, 157.5, 205.3. MS (EI): m/z (%) = 394 (100) [M⁺], 393 (31), 380 (17), 379 (58), 324 (28), 323 (90), 309 (17), 308 (20), 307 (14), 44 (13). HRMS (EI): m/z calcd for C₂₇H₂₆N₂O: 394.2045; found: 394.2048. Compound 3bd (1:1 mixture of E and Z isomers): dark red solid; mp 120–122 °C. ¹H NMR (400 MHz, CDCl₃): δ = 0.85 (d, J = 8.0 Hz, 3 H), 1.20 (t, J = 7.2 Hz, 3 H), 1.25 (t, J = 7.2 Hz, 3 H), 1.37 (d, J = 7.6 Hz, 3 H), 2.13 (s, 6 H), 2.28 (s, 6 H), 2.97 (q, J = 7.2 Hz, 2 H), 3.10 (q, J = 7.2 Hz, 2 H), 4.19 (q, J = 7.6 Hz, 1 H), 4.69 (q, J = 8.0 Hz, 1 H), 6.08 (d, J = 2.0 Hz, 1 H), 6.13 (d, J = 2.0 Hz, 1 H), 6.99 (dd, J = 6.0, 1.6 Hz, 1 H), 7.01 (dd, J = 6.4, 2.0 Hz, 1 H), 7.13–7.17 (m, 2 H), 7.21–7.30 (m, 6 H), 7.30–7.36 (m, 9 H), 7.46 (d, J = 8.0 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 7.7, 7.8, 10.8, 14.0, 29.8, 31.7, 33.1, 34.1, 100.6, 102.6, 109.5, 109.8, 118.6, 119.6, 127.0, 127.1, 127.7, 127.8, 128.8, 129.0, 129.3, 129.8, 129.9, 130.0, 131.8, 132.1, 136.0, 136.1, 136.3, 137.5, 137.8, 138.4, 140.7, 143.1, 143.9, 156.7, 161.3, 203.4, 204.4. MS (EI): m/z (%) = 394 (100) [M⁺], 380 (10), 379 (21), 366 (22), 365 (51), 338 (26), 337 (98), 323 (19), 322 (24), 321 (17), 309 (14), 308 (17), 307 (15), 57 (16). HRMS (EI): m/z calcd for C₂₇H₂₆N₂O: 394.2045; found: 394.2050. Compound 3ca: yellow solid; mp 179–181 °C (dec.). ¹H NMR (400 MHz, CDCl₃): δ = 2.15 (s, 6 H), 3.55 (d, J = 2.8 Hz, 1 H), 4.07 (d, J = 2.8 Hz, 1 H), 5.86 (d, J = 2.0 Hz, 1 H), 6.92 (d, J = 2.0 Hz, 1 H), 7.28 (m, 3 H), 7.50 (m, 2 H), 7.63 (m, 1 H), 8.09 (m, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 17.9, 89.9, 11.2, 121.7, 128.4, 128.9, 129.7, 130.2, 130.3, 134.2, 134.5, 134.7, 135.2, 135.4, 136.3, 136.6, 137.0, 159.6, 191.6. MS (EI): m/z (%) = 422 (77), 420 (100) [M⁺], 407 (46), 405 (67), 393 (36), 391 (52), 317 (67), 315 (97), 300 (33). HRMS (EI): m/z calcd for C₂₄H₁₈N₂OCl₂: 420.0796; found: 420.0800. Compound 3cc: brown solid; mp 90–92 °C. ¹H NMR (400 MHz, CDCl₃): δ = 1.22 (d, J = 6.8 Hz, 6 H), 2.10 (s, 6 H), 3.56 (d, J = 2.0 Hz, 1 H), 3.74 (sept, J = 6.8 Hz, 1 H), 4.66 (d, J = 2.0 Hz, 1 H), 5.75 (d, J = 2.0 Hz, 1 H), 6.88 (d, J = 2.0 Hz, 1 H), 7.23–7.31 (m, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 17.8, 18.1, 37.3, 90.1, 110.1, 121.3, 128.0, 129.2, 129.6, 130.2, 134.5, 135.4, 136.6, 137.0, 137.6, 156.7, 204.6. MS (EI): m/z (%) = 388 (63), 386 (89) [M⁺], 373 (48), 371 (72), 317 (69), 315 (100), 300 (29). HRMS (EI): m/z calcd for C₂₁H₂₀N₂OCl₂: 386.0953; found: 386.0959. Compound 3da: yellow-green solid; mp 144–146 °C. ¹H NMR (400 MHz, CDCl₃): δ = 2.21 (s, 3 H), 3.53 (d, J = 2.8 Hz, 1 H), 4.01 (d, J = 2.8 Hz, 1 H), 6.00 (d, J = 2.0 Hz, 1 H), 6.81 (dd, J = 8.4, 2.0 Hz, 1 H), 7.17–7.22 (m, 1 H), 7.32 (d, J = 8.4 Hz, 1 H), 7.41–7.45 (m, 2 H), 7.46–7.54 (m, 3 H), 7.64 (m, 1 H), 8.01 (m, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 17.6, 89.5, 112.1, 120.8, 128.9, 129.2, 129.4, 129.8, 130.3, 130.5, 131.2, 132.9, 134.5, 134.8, 136.0, 136.3, 136.7, 136.9, 137.3, 159.4, 192.3. MS (EI): m/z (%) = 374 (49), 372 (100) [M⁺], 359 (42), 345 (36), 269 (20), 267 (55), 105 (66), 91 (14), 77 (56). HRMS (EI): m/z calcd for C₂₃H₁₇N₂OCl: 372.1029; found: 372.1028. Compound 3ea: dark brown oil. ¹H NMR (400 MHz, CDCl₃): δ = 2.17 (s, 6 H), 3.53 (d, J = 2.4 Hz, 1 H), 3.99 (d, J = 2.4 Hz, 1 H), 5.71 (dd, J = 10.4, 2.4 Hz, 1 H), 6.51–6.57 (m, 1 H), 7.36–7.41 (m, 1 H), 7.44–7.47 (m, 1 H), 7.40–7.53 (m, 3 H), 7.61–7.66 (m, 1 H), 7.86–7.89 (m, 1 H), 8.07–8.10 (m, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 17.8, 26.0, 88.3, 96.8, 98.9 (d, J _CF = 29 Hz), 107.5 (d, J _CF = 23 Hz), 127.1, 128.9, 129.5, 130.1 (d, J _CF = 13 Hz), 131.1 (d, J _CF = 11 Hz), 132.4, 134.5 (d, J _CF = 10 Hz), 134.9, 135.7, 136.4 (d, J _CF = 12 Hz), 136.8, 158.5, 163.2, 165.7, 192.4. ESI-MS (MeOH): m/z = 371 [M + H]⁺. ESI-HRMS (MeOH): m/z calcd for C₂₄H₂₀N₂OF: 371.1560; found: 371.1552. Compound 3eb: dark red solid; mp 105–108 °C. ¹H NMR (400 MHz, CDCl₃): δ = 2.11 (s, 6 H), 2.60 (s, 3 H), 3.56 (d, J = 1.6 Hz, 1 H), 4.89 (d, J = 1.6 Hz, 1 H), 5.57 (dd, J = 10.4, 2.4 Hz, 1 H), 6.47–6.53 (m, 1 H), 7.22–7.30 (m, 3 H), 7.35–7.39 (m, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 17.8, 27.8, 88.8, 98.7 (d, J _CF = 28 Hz), 107.4 (d, J _CF = 23 Hz), 128.8 (d, J _CF = 2 Hz),, 129.3, 130.1, 131.9 (d, J _CF = 11 Hz),, 134.0, 134.8, 136.8, 137.4 (d, J _CF = 10 Hz), 154.0 (d, J _CF = 3 Hz), 165.4 (d, J _CF = 248 Hz), 199.4. MS (EI): m/z (%) = 308 (50) [M⁺], 293 (93), 265 (100), 250 (56), 236 (18). HRMS (EI): m/z calcd for C₁₉H₁₇N₂OF: 308.1325; found: 308.1321. Compound 3fa: dark brown solid; mp 89–91 °C. ¹H NMR (400 MHz, CDCl₃): δ = 2.17 (s, 6 H), 3.46 (d, J = 2.0 Hz, 1 H), 3.66 (s, 3 H), 3.95 (d, J = 2.0 Hz, 1 H), 5.55 (d, J = 2.8 Hz, 1 H), 6.42 (dd, J = 8.8, 2.8 Hz, 1 H), 7.13–7.18 (m, 2 H), 7.36 (d, J = 8.8 Hz, 1 H), 7.59–7.64 (m, 1 H), 7.42–7.52 (m, 2 H), 7.86–7.90 (m, 1 H), 8.07–8.11 (m, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 17.8, 55.5, 87.0, 96.8, 97.8, 105.3, 125.4, 127.1, 128.4, 128.8, 129.2, 129.9, 130.3, 130.8, 134.2, 136.1, 136.9, 156.5, 162.0, 192.8. MS (EI): m/z (%) = 382 (66) [M⁺], 367 (62), 353 (62), 277 (81), 248 (56), 105 (100), 77 (60). HRMS (EI): m/z calcd for C₂₅H₂₂N₂O₂: 382.1681; found: 382.1685. Compound 3gb: dark red solid; mp 70–73 °C. ¹H NMR (400 MHz, CDCl₃): δ = 1.17 (t, J = 7.6 Hz, 3 H), 2.45–2.53 (m, 2 H), 2.59 (s, 3 H), 3.56 (d, J = 1.6 Hz, 1 H), 4.81 (d, J = 1.6 Hz, 1 H), 5.88 (d, J = 2.0 Hz, 1 H), 6.76 (dd, J = 8.4, 2.0 Hz, 1 H), 7.09 (dd, J = 7.6, 1.2 Hz, 1 H), 7.29 (d, J = 8.4 Hz, 1 H), 7.39–7.54 (m, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 13.7, 23.6, 27.8, 90.5, 112.4, 120.6, 128.4, 129.2, 129.5, 129.8, 130.9, 131.0, 135.8, 136.3, 137.3, 137.9, 142.5, 155.3, 199.4. MS (EI): m/z (%) = 326 (24), 324 (37) [M⁺], 311 (44), 309 (100), 283 (23), 281 (44), 266 (39), 255 (32). HRMS (EI): m/z calcd for C₁₉H₁₇N₂OCl: 324.1029; found: 324.1027. Compound 3ha: brown solid; mp 156–159 °C. ¹H NMR (400 MHz, CDCl₃): δ = 1.37 (s, 9 H), 3.54 (d, J = 2.4 Hz, 1 H), 4.15 (d, J = 2.4 Hz, 1 H), 5.98 (d, J = 2.0 Hz, 1 H), 6.81 (dd, J = 8.4, 2.0 Hz, 1 H), 7.03–7.06 (m, 1 H), 7.31 (d, J = 8.4 Hz, 1 H), 7.40–7.53 (m, 4 H), 7.61–7.66 (m, 1 H), 7.69–7.72 (m, 1 H), 8.05–8.09 (m, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 32.0, 36.3, 91.9, 113.9, 120.8, 127.2, 128.8, 128.9, 129.7, 130.2, 130.3, 131.1, 131.5, 131.9, 132.4, 134.5, 134.7, 135.2, 136.0, 138.4, 139.5, 148.4, 159.2, 192.2. MS (EI): m/z (%) = 416 (11), 414 (71) [M⁺], 402 (13), 400 (37), 359 (20), 357 (49), 311 (47), 309 (99), 105 (100), 91 (41), 77 (81). HRMS (EI): m/z calcd for C₂₆H₂₃N₂OCl: 414.1499; found: 414.1489. Compound 6: green solid; mp 116–118 °C. ¹H NMR (400 MHz, CDCl₃): δ = 1.10 (s, 3 H), 1.12 (d, J = 6.8 Hz, 6 H), 2.34 (s, 3 H), 4.10 (sept, J = 6.8 Hz, 1 H), 5.23 (s, 1 H), 5.89 (d, J = 2.0 Hz, 1 H), 6.75 (dd, J = 8.4, 2.0 Hz, 1 H), 6.85 (dd, J = 7.2, 2.0 Hz, 1 H), 7.09–7.23 (m, 7 H), 7.48 (d, J = 8.4 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 17.9, 18.3, 19.2, 19.9, 34.5, 84.2, 112.4, 118.6, 125.7, 127.2, 128.2, 128.7, 129.1, 132.1, 134.5, 137.4, 138.8, 139.4, 141.2, 143.6, 150.7, 208.3. MS (EI): m/z (%) = 432 (5) [M^+•], 416 (13), 391 (11), 389 (30), 364 (11), 363 (41), 362 (33), 361 (88), 357 (26), 356 (17), 355 (67), 337 (12), 333 (13), 327 (13), 257 (12), 255 (11), 106 (12), 105 (100), 77 (43), 44 (20). HRMS (EI): m/z calcd for C₂₆H₂₅N₂O₂Cl: 432.1605; found: 432.1588. Compound 7: orange solid; mp 156–158 °C. ¹H NMR (500 MHz, CDCl₃): δ = 1.39 (s, 3 H), 2.46 (s, 3 H), 4.93 (s, 1 H), 6.05 (d, J = 2.0 Hz, 1 H), 6.80–6.83 (m, 2 H), 7.06–7.15 (m, 5 H), 7.26–7.29 (m, 2 H), 7.47–7.52 (m, 3 H), 7.60–7.64 (m, 1 H), 8.13–8.17 (m, 2 H). ¹³C NMR (125 MHz, CDCl₃): δ = 18.3, 20.0, 84.3, 113.2, 119.0, 126.2, 127.8, 128.2, 128.3, 128.5, 129.1, 131.1, 131.6, 133.7, 135.4, 135.5, 136.6, 138.2, 138.5, 140.7, 142.0, 153.4, 193.3. ESI-MS (MeOH): m/z = 489 [M + Na]⁺, 955 [2 M + Na]⁺, 1421 [3 M + Na]⁺. ESI-HRMS (MeOH): m/z calcd for C₂₉H₂₃N₂O₂NaCl: 489.1346; found: 489.1338.