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Synlett 2015; 26(17): 2418-2424
DOI: 10.1055/s-0034-1380538
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© Georg Thieme Verlag Stuttgart · New York

Synthesis of Three New Tricyclic Ring Systems: Pyrrolotriazepines Condensed with an Imidazole, a Triazole, or a Tetrazole Ring

Mátyás Milen
Egis Pharmaceuticals Plc., Chemical Research Division, P.O. Box 100, 1475 Budapest, Hungary   Email: volk.balazs@egis.hu
,
Tamás Földesi
Egis Pharmaceuticals Plc., Chemical Research Division, P.O. Box 100, 1475 Budapest, Hungary   Email: volk.balazs@egis.hu
,
András Dancsó
Egis Pharmaceuticals Plc., Chemical Research Division, P.O. Box 100, 1475 Budapest, Hungary   Email: volk.balazs@egis.hu
,
Gyula Simig
Egis Pharmaceuticals Plc., Chemical Research Division, P.O. Box 100, 1475 Budapest, Hungary   Email: volk.balazs@egis.hu
,
Balázs Volk*
Egis Pharmaceuticals Plc., Chemical Research Division, P.O. Box 100, 1475 Budapest, Hungary   Email: volk.balazs@egis.hu
› Author Affiliations
Further Information

Publication History

Received: 10 January 2015

Accepted after revision: 17 March 2015

Publication Date:
23 April 2015 (online)

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Dedicated to the memory of Professor Manfred Schlosser in honour of his scientific achievements

Abstract

In a previous paper, we have disclosed a practical synthesis of 1-aryl-3H-pyrrolo[2,1-d][1,2,5]triazepin-4(5H)-ones. Now, these compounds have been used as the starting materials for the synthesis of three new ring systems, pyrrolotriazepines condensed with an imidazole, a triazole, or a tetrazole ring. The newly synthesized compounds are structurally closely related to tricyclic derivatives known from the literature as strong anticonvulsant agents.

Key words

nitrogen - ring closure - condensation - reduction - alkylation - sulfur

Supporting Information

    Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0034-1380538. Analytical data and spectral characterization of new compounds 11i, 12b–g, 13b–g, 14b–e, 14g–i, 15b–t, 15v–y, 16b, 17b–d, 17f,g, 18b–d, 18f–h are included, as well as X-ray structures, CIF structure files (atomic coordinates, bond lengths, bond angles, torsion angles), and conditions of the single-crystal X-ray measurements for compounds 15j and 18a.
  • Supporting Information
 

  • References and Notes

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  • 13 General Procedure for the Preparation of 1-Aryl-3-[2-aryl/aralkyl-2-oxoethyl]-3H-pyrrolo[2,1-d][1,2,5]triazepin-4(5H)-ones – Preparation of Compounds 12a–h The appropriate pyrrolotriazepinone compound 11 (3.0 mmol) was dissolved in a mixture of MeCN (60 mL) and CH2Cl2 (60 mL), then Cs2CO3 (1.17 g, 3.6 mmol, 1.2 equiv) and the appropriate acetophenone derivative (3.9 mmol, 1.3 equiv) were added. The mixture was stirred at r.t. until the starting material disappeared on TLC (24 h). The reaction mixture was filtered and evaporated. The residue was taken up with a 1:1 mixture of CH2Cl2 and H2O, after separation the aqueous layer was washed with CH2Cl2, then the collected organic layer was washed with H2O. The crude material was obtained after drying on MgSO4 and evaporating. The residue was purified by flash chromatography. 1-(4-Fluorophenyl)-3-(2-oxo-2-phenylethyl)-3H-pyrrolo[2,1-d][1,2,5]triazepin-4(5H)-one (12a) Yield 1.02 g (94%), white crystals, mp 180–181 °C (EtOH). IR (KBr): 1698, 1652, 1225, 753 cm–1. 1H NMR (500 MHz, DMSO-d 6): δ = 8.02–8.00 (m, 2 H), 7.76–7.74 (m, 2 H), 7.70–7.67 (m, 1 H), 7.58–7.54 (m, 2 H), 7.33–7.31 (m, 1 H), 7.29–7.25 (m, 2 H), 6.34–6.33 (m, 1 H), 6.29–6.28 (m, 1 H), 5.33 (s, 2 H), 4.97 (s, 2 H) ppm. 13C NMR (125 MHz, DMSO-d 6): δ = 193.2, 165.2, 163.6 (d, J = 248.3 Hz), 152.1, 134.9, 134.0, 133.4 (d, J = 2.9 Hz), 131.8 (d, J = 8.8 Hz), 129.0, 128.1, 125.6, 124.9, 115.3 (d, J = 22.0 Hz), 114.1, 110.0, 57.5, 51.5 ppm. Anal. Calcd for C21H16FN3O2 (361.38): C, 69.80; H, 4.46; N, 11.63. Found: C, 69.43; H, 4.55; N, 11.63. 3-[2-(4-Chlorophenyl)-2-oxoethyl]-1-(4-nitrophenyl)-3H-pyrrolo[2,1-d][1,2,5]triazepin-4(5H)-one (12h) Yield 1.00 g (79%), yellow crystals, mp 161–162 °C (i-PrOH). IR (KBr,): 1699, 1676, 1589, 1569, 1519, 1347 cm–1. 1H NMR (400 MHz, DMSO-d 6): δ = 8.31–8.28 (m, 2 H), 8.05–8.03 (m, 2 H), 7.98–7.96 (m, 2 H), 7.66–7.63 (m, 2 H), 7.36–7.35 (m, 1 H), 6.37–6.36 (m, 1 H), 6.34–6.32 (m, 1 H), 5.39 (s, 2 H), 5.04 (s, 2 H) ppm. 13C NMR (100 MHz, DMSO-d 6): δ = 192.4, 165.1, 150.8, 148.6, 143.0, 138.9, 133.5, 130.7, 130.0, 129.2, 125.3, 125.2, 123.5, 114.3, 110.4, 57.8, 51.4 ppm. Anal Calcd for C21H15ClN4O4 (422.82): C, 59.65; H, 3.58; Cl, 8.38; N, 13.25. Found: C, 59.61; H, 3.59; Cl, 8.42; N, 13.27
  • 14 General Procedure for the Preparation of 2-Aryl-6-aryl-imidazo[1,2-b]pyrrolo[1,2-e][1,2,5]triazepines – Preparation of Compounds 13a–h The appropriate compound 12 (0.75 mmol) and NH4OAc (0.58 g, 7.5 mmol, 10 equiv) were refluxed in AcOH (10 mL) until the starting material disappeared on TLC (6–19 h). After the reaction was complete, the mixture was cooled and poured onto ice, and the pH was set alkaline with a 40 w/w% NaOH solution. After cooling the mixture was extracted three times with CH2Cl2, then the collected organic layer was washed with H2O until its pH turned to neutral. The organic solution was dried over MgSO4 and evaporated. The crude material was purified by flash chromatography. 6-(4-Fluorophenyl)-2-phenyl-11H-imidazo[1,2-b]pyrrolo[1,2-e][1,2,5]triazepine (13a) Yield 0.17 g (66%), white crystals, mp 177–178 °C (EtOH). IR (KBr): 1600, 1412, 744, 729 cm–1. 1H NMR (500 MHz, CDCl3): δ = 7.86–7.83 (m, 2 H), 7.77–7.75 (m, 2 H), 7.60 (s, 1 H), 7.40–7.37 (m, 2 H), 7.27–7.24 (m, 1 H), 7.17–7.13 (m, 2 H), 7.00–6.99 (m, 1 H), 6.35–6.34 (m, 1 H), 6.28–6.27 (m, 1 H), 5.35 (s, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 164.4 (d, J = 251.5 Hz), 154.3, 139.4, 138.6, 133.6 (d, J = 3.4 Hz), 133.5, 132.0 (d, J = 8.8 Hz), 128.6, 127.1, 125.9, 125.8, 124.7, 119.5, 117.3, 115.3 (d, J = 21.5 Hz), 110.1, 46.4 ppm. Anal. Calcd for C21H15FN4 (342.38): C, 73.67; H, 4.42; N, 16.36. Found: C, 73.40; H, 4.49; N, 16.30. 2-(4-Chlorophenyl)-6-(4-nitrophenyl)-11H-imidazo[1,2-b]pyrrolo[1,2-e][1,2,5]triazepine (13h) Yield 0.19 g (43%), yellow crystals, mp 283–284 °C (MeCN). IR (KBr): 1562, 1520, 1410, 1352, 727 cm–1. 1H NMR (400 MHz, DMSO-d 6): δ = 8.41–8.38 (m, 2 H), 8.15 (s, 1 H), 8.06–8.04 (m, 2 H), 7.85–7.82 (m, 2 H), 7.49–7.48 (m, 1 H), 7.45–7.43 (m, 2 H), 6.35–6.33 (m, 1 H), 6.32–6.31 (m, 1 H), 5.62 (s, 2 H) ppm. 13C NMR (100 MHz, DMSO-d 6): δ = 153.0, 148.8, 143.5, 139.7, 137.4, 132.6, 131.4, 131.3, 128.8, 127.4, 126.1, 125.3, 123.6, 119.0, 118.5, 110.4, 45.3 ppm. Anal. Calcd for C21H14ClN5O2 (403.82): C, 62.45; H, 3.49; Cl, 8.78; N, 17.34. Found: C, 62.55; H, 3.49; Cl, 8.66; N, 17.29. 4-{2-(4-Chlorophenyl)-11H-imidazo[1,2-b]pyrrolo[1,2-e][1,2,5]triazepin-6-yl}aniline (13i) 4-Nitro derivative 13h (0.34 g, 0.84 mmol) was dissolved in a mixture of CH2Cl2 (45 mL) and MeOH (45 mL). To this solution, N2H4·H2O (0.20 mL, 0.21 g, 4.20 mmol, 5 equiv) and Raney nickel (0.35 g) were added. The reaction was followed by LC–MS. After consumption of the starting material (48 h), the mixture was filtered on Celite and evaporated under reduced pressure. The crude material was purified by flash chromatography to give 0.29 g (91%) of 13i as pale yellow crystals, mp 233–235 °C (MeCN). IR (KBr): 3342, 1622, 1605, 1434, 1410, 1175, 735 cm–1. 1H NMR (400 MHz, DMSO-d 6): δ = 8.01 (s, 1 H), 7.81–7.79 (m, 2 H), 7.56–7.53 (m, 2 H), 7.43–7.40 (m, 2 H), 7.37–7.35 (m, 1 H), 6.64–6.62 (m, 2 H), 6.32–6.31 (m, 1 H), 6.28–6.26 (m, 1 H), 5.78 (br s, 2 H), 5.45 (s, 2 H) ppm. 13C NMR (100 MHz, DMSO-d 6): δ = 156.2, 152.0, 140.3, 136.8, 133.0, 131.5, 131.0, 128.7, 126.0, 125.8, 125.3, 123.5, 118.0, 117.8, 113.0, 109.3, 45.0 ppm. Anal Calcd for C21H16ClN5 (373.84): C, 67.47; H, 4.31; Cl 9.48; N, 18.78. Found: C, 67.48; H, 4.34; 9.15; N, 18.86.
  • 15 Csuzdi E, Migléczi K, Hazai I, Berzsenyi P, Pallagi I, Horváth G, Lengyel G, Sólyom S. Bioorg. Med. Chem. Lett. 2005; 15: 4662
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  • 16 General Procedure for the Preparation of 1-Aryl-3H-pyrrolo[2,1-d][1,2,5]triazepine-4(5H)-thiones – Preparation of Compounds 14a–i Lawesson’s reagent [2,4-bis(4-methoxyphenyl)-2,4-dithioxo-1,3,2,4-dithiadiphosphetane] (0.69 g, 1.7 mmol) was added to a solution in dry toluene (80 mL) of the suitable 1-aryl-3H-pyrrolo[2,1-d][1,2,5]triazepin-4(5H)-one derivative 11a–i (3.1 mmol). The mixture was stirred at reflux temperature until the starting material disappeared on TLC (1–2 h). After the reaction was complete, the mixture was cooled to r.t., and the solvent was removed under reduced pressure. The crude material was purified by flash chromatography. 1-(4-Fluorophenyl)-3H-pyrrolo[2,1-d][1,2,5]triazepine-4(5H)-thione (14a) Yield 0.57 g (71%), yellow crystals, mp 214–216 °C (decomp., MeCN). IR (KBr): 3192, 1414, 1378, 846, 738 cm–1. 1H NMR (500 MHz, DMSO-d 6): δ = 12.82 (br s, 1 H), 7.78–7.75 (m, 2 H), 7.34–7.31 (m, 3 H), 6.36–6.35 (m, 1 H), 6.31–6.30 (m, 1 H), 5.11 (s, 2 H) ppm. 13C NMR (125 MHz, DMSO-d 6): δ = 191.1, 163.8 (d, J = 248.5 Hz), 154.5, 133.3 (d, J = 2.9 Hz), 131.7 (d, J = 9.3 Hz), 125.0 (two signals: 125.05, 124.95), 115.5 (d, J = 22.0 Hz), 115.1, 110.5, 57.7 ppm. Anal. Calcd for C13H10FN3S (259.31): C, 60.22; H, 3.89; N, 16.20; S, 12.37. Found: C, 60.29; H, 3.92; N, 16.32; S, 12.37. 1-Phenyl-3H-pyrrolo[2,1-d][1,2,5]triazepine-4(5H)-thione (14f) Yield 0.59 g (79%), yellow crystals, mp 229–230 °C (decomp., MeCN). IR (KBr): 3184, 1387, 1110, 703 cm–1. 1H NMR (500 MHz, DMSO-d 6): δ = 12.82 (br s, 1 H), 7.73–7.71 (m, 2 H), 7.56–7.53 (m, 1 H), 7.50–7.47 (m, 2 H), 7.31–7.30 (m, 1 H), 6.35 (dd, J 1 = 2.6 Hz, J 2 = 4.0 Hz, 1 H), 6.28 (dd, J 1 = 1.5 Hz, J 2 = 3.8 Hz, 1 H), 5.11 (s, 2 H) ppm. 13C NMR (125 MHz, DMSO-d 6): δ = 191.1, 155.5, 136.8, 131.0, 129.4, 128.5, 125.2, 124.8, 115.1, 110.4, 57.8 ppm. Anal. Calcd for C13H11N3S (241.32): C, 64.71; H, 4.59; N, 17.41; S, 13.29. Found: C, 64.81; H, 4.47; N, 17.37; S, 13.05
  • 17 General Procedure for the Preparation of 3-Unsubstituted/Alkyl/Aryl-6-aryl-pyrrolo[1,2-e][1,2,4]triazolo[4,3-b][1,2,5]triazepines – Preparation of Compounds 15a–x The appropriate pyrrolotriazepinethione 14 (0.77 mmol) or S-methyl derivative 16 (0.77 mmol) was dissolved in BuOH (15 mL), than the appropriate acid hydrazide (2.31 mmol, 3 equiv) was added. When the S-methyl derivative was used as starting material, the mixture was acidified by 0.05 mL concd HCl. The reaction mixture was refluxed until the starting material disappeared on TLC (4–24 h). The solvent was evaporated, then the residue was taken up into CH2Cl2. It was washed twice with 1% (w/w) aq HCl solution, then the organic layer was washed with H2O. The solution was dried over MgSO4, filtered, and evaporated. The crude material was purified by flash chromatography. 6-(4-Fluorophenyl)-11H-pyrrolo[1,2-e][1,2,4]triazolo[4,3-b][1,2,5]triazepine (15a) Yield 0.17 g (method A, 85%), off-white crystals, mp 278–280 °C (EtOH–MeCN, 1:1). IR (KBr): 1600, 1486, 1406, 1086, 747 cm–1. 1H NMR (500 MHz, DMSO-d 6): δ = 8.90 (s, 1 H), 7.86–7.84 (m, 2 H), 7.51–7.49 (m, 1 H), 7.40–7.36 (m, 2 H), 6.32–6.31 (m, 2 H), 5.74 (s, 2 H) ppm. 13C NMR (125 MHz, DMSO-d 6): δ = 164.0 (d, J = 249.0 Hz), 155.5, 146.5, 144.3, 133.4 (d, J = 2.9 Hz), 132.5 (d, J = 9.3 Hz), 128.1, 125.4, 120.5, 115.5 (d, J = 22.0 Hz), 110.2, 42.9 ppm. Anal. Calcd for C14H10FN5 (267.27): C, 62.92; H, 3.77; N, 26.20. Found: C, 62.63; H, 3.61; N, 26.44. 3-(5-Methylisoxazol-3-yl)-6-phenyl-11H-pyrrolo[1,2-e][1,2,4]triazolo[4,3-b][1,2,5]triazepine (15u) Yield 0.24 g (method B, 95%), off-white crystals, mp 235–237 °C (MeCN). IR (KBr): 1410, 1329, 737, 703 cm–1. 1H NMR (500 MHz, DMSO-d 6): δ = 7.91–7.89 (m, 2 H), 7.64–7.61 (m, 1 H), 7.57–7.56 (m, 2 H), 7.55–7.54 (m, 1 H), 6.87 (s, 1 H), 6.38–6.35 (m, 2 H), 5.82 (s, 2 H), 2.58 (s, 3 H) ppm. 13C NMR (125 MHz, DMSO-d 6): δ = 170.8, 157.4, 152.1, 149.1, 145.0, 136.8, 131.6, 130.6, 128.5, 128.1, 125.2, 120.5, 110.4, 102.4, 42.9, 12.0 ppm. Anal. Calcd for C18H14N6O (330.35): C, 65.45; H, 4.27; N, 25.44. Found: C, 65.31; H, 4.39; N, 25.80.
  • 18 General Procedure for the Preparation of 1-Aryl-4-(methylsulfanyl)-5H-pyrrolo[2,1-d][1,2,5]triazepines – Preparation of Compounds 16a–f The appropriate pyrrolotriazepinethione 14 (3.16 mmol) was dissolved in a 1:1 mixture of MeCN and CH2Cl2 (100 mL), then Cs2CO3 (1.24 g, 3.80 mmol) and MeI (0.22 mL, 3.48 mmol) were added. The reaction mixture was stirred overnight at r.t., then filtered and evaporated. The residue was dissolved in CH2Cl2 and washed with H2O. The organic layer was extracted with H2O again, dried over MgSO4, filtered, and evaporated. The crude material was recrystallized from the appropriate solvent (if necessary, prior to recrystallization, it was purified by chromatography). 1-(4-Fluorophenyl)-4-(methylsulfanyl)-5H-pyrrolo[2,1-d][1,2,5]triazepine (16a) Yield 0.85 g (98%), white crystals, mp 196–198 °C (EtOH). IR (KBr): 1505, 1412, 843, 718 cm–1. 1H NMR (500 MHz, DMSO-d 6): δ = 7.81–7.78 (m, 2 H), 7.30–7.26 (m, 2 H), 7.17–7.16 (m, 1 H), 6.31–6.29 (m, 2 H), 4.79 (s, 2 H), 2.37 (s, 3 H) ppm. 13C NMR (125 MHz, DMSO-d 6): δ = 163.6 (d, J = 247.6 Hz), 154.0, 149.7, 134.3 (d, J = 2.9 Hz), 131.4 (d, J = 8.8 Hz), 125.2, 122.7, 115.4 (d, J = 21.5 Hz), 113.1, 109.9, 49.3, 13.3 ppm. Anal. Calcd for C14H12FN3S (273.33): C, 61.52; H, 4.43; N, 15.37; S, 11.73. Found: C, 61.34; H, 4.50; N, 15.42; S, 11.70. 4-(Methylsulfanyl)-1-phenyl-5H-pyrrolo[2,1-d][1,2,5]triazepine (16f) Yield 0.62 g (77%), off-white crystals, mp 186–188 °C (EtOH). IR (KBr): 1554, 1536, 1409, 720, 705 cm–1. 1H NMR (500 MHz, CDCl3): δ = 7.88–7.86 (m, 2 H), 7.47–7.44 (m, 1 H), 7.42–7.38 (m, 2 H), 6.81–7.80 (m, 1 H), 6.41–7.40 (m, 1 H), 6.36–7.34 (m, 1 H), 4.55 (br s, 2 H), 2.46 (s, 3 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 153.4, 152.0, 137.8, 130.4, 129.6, 128.1, 126.0, 121.3, 114.1, 110.1, 50.2, 13.8 ppm. Anal. Calcd for C14H13N3S (255.34): C, 65.85; H, 5.13; N, 16.46; S, 12.56. Found: C, 65.70; H, 5.18; N, 16.56; S, 12.58.
  • 19 General Procedure for the Preparation of 1-Aryl-4-hydrazino-5H-pyrrolo[2,1-d][1,2,5]triazepines – Preparation of Compounds 17a–g The appropriate pyrrolotriazepinethione 14 (2.0 mmol) and N2H4·H2O (0.29 mL, 0.30 g, 6.0 mmol, 3 equiv) were stirred at r.t. in THF (30 mL) until the starting material disappeared on TLC (1–1.5 h). The solvent was evaporated, then the residue was purified by flash chromatography. 1-(4-Fluorophenyl)-4-hydrazino-5H-pyrrolo[2,1-d][1,2,5]triazepine (17a) Yield 0.46 g (89%), pale yellow crystals, mp 184–186 °C (EtOH). IR (KBr): 3281, 3143, 1509, 1229, 1077, 839 cm–1. 1H NMR (500 MHz, DMSO-d 6): δ = 9.32 (br s, 1 H), 7.71–7.68 (m, 2 H), 7.25–7.22 (m, 2 H), 7.13–7.12 (m, 1 H), 6.18–6.16 (m, 1 H), 6.07–6.06 (m, 1 H), 5.14 (br s, 2 H), 4.67 (s, 2 H) ppm. 13C NMR (125 MHz, DMSO-d 6): δ = 162.6 (d, J = 246.1 Hz), 143.8, 141.9, 135.4 (d, J = 2.9 Hz), 130.5 (d, J = 8.8 Hz), 126.2, 122.9, 115.0 (d, J = 21.5 Hz), 112.6, 108.9, 50.2 ppm. Anal Calcd for C13H12FN5 (257.27): C, 60.69; H, 4.70; N, 27.22. Found: C, 60.81; H, 4.77; N, 26.85. 4-Hydrazino-1-phenyl-5H-pyrrolo[2,1-d][1,2,5]triazepine (17e) Yield 0.42 g (88%), white crystals, mp 165–166 °C (EtOH). IR (KBr): 3292, 3187, 1640, 1380 cm–1. 1H NMR (500 MHz, CDCl3): δ = 9.35 (br s, 1 H), 7.67–7.66 (m, 2 H), 7.41–7.39 (m, 3 H), 7.12–7.11 (m, 1 H), 6.18–6.17 (m, 1 H), 6.06–6.05 (m, 1 H), 5.16 (br s, 2 H), 4.68 (s, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 144.9, 142.0, 139.0, 129.0, 128.6, 128.2, 126.4, 122.8, 112.7, 108.9, 50.2 ppm. Anal Cald for C13H13N5 (239.28): C, 65.26; H, 5.48; N, 29.27. Found: C, 65.25; H, 5.42; N, 29.34.
  • 20 General Procedure for the Preparation of 6-Aryl-11H-pyrrolo[1,2-e]tetrazolo[1,5-b][1,2,5]triazepines – Preparation of Compounds 18a–g The appropriate hydrazine 17 (0.8 mmol) was suspended in a 0.5 M aq HCl solution (5 mL) and was cooled in ice bath. NaNO2 (83 mg, 1.2 mmol, 1.5 equiv) in H2O (15 mL) was added dropwise to the mixture, then the mixture was stirred in ice bath for a further 2 h. After that, the pH was set alkaline with a 10 w/w% NaHCO3 solution. The mixture was filtered, and the residue was washed with ice-cold water. The raw material was purified by flash chromatography. 6-(4-Fluorophenyl)-11H-pyrrolo[1,2-e]tetrazolo[1,5-b][1,2,5]triazepine (18a) Yield 0.17 g (80%), pale yellow crystals, mp 287–288 °C (MeCN). IR (KBr): 1600, 1553, 1402, 1228, 755 cm–1. 1H NMR (500 MHz, DMSO-d 6): δ = 7.92–7.89 (m, 2 H), 7.58–7.57 (m, 1 H), 7.43–7.40 (m, 2 H), 6.44 (dd, J 1 = 1.6 Hz, J 2 = 4.0 Hz, 1 H), 6.40 (dd, J 1 = 2.6 Hz, J 2 = 4.0 Hz, 1 H), 5.99 (s, 2 H) ppm. 13C NMR (125 MHz, DMSO-d 6): δ = 164.3 (d, J = 249.5 Hz), 156.7, 146.7, 133.0 (d, J = 8.8 Hz), 129.7, 125.4, 122.6, 115.7 (d, J = 22.0 Hz), 111.0, 41.0 ppm. Anal Calcd for C13H9FN6 (268.26): C, 58.21; H, 3.38; N, 31.33. Found: C, 58.25; H, 3.46; N, 31.21. 6-Phenyl-11H-pyrrolo[1,2-e]tetrazolo[1,5-b][1,2,5]triazepine (18e) Yield 0.18 g (89%), off-white crystals, mp 228–229 °C (MeCN). IR (KBr): 1554, 1401, 757, 705 cm–1. 1H NMR (500 MHz, DMSO-d 6): δ = 7.87–7.81 (m, 2 H), 7.67–7.54 (m, 4 H), 6.43–6.37 (m, 2 H), 5.99 (s, 2 H) ppm. 13C NMR (125 MHz, DMSO-d 6): δ = 157.7, 146.7, 136.3, 131.8, 130.5, 129.6, 128.6, 125.5, 122.6, 111.0, 41.1 ppm. Anal Calcd for C13H10N6 (250.26): C, 62.39; H, 4.03; N, 33.58. Found: C, 62.46; H, 3.99; N, 33.45.