2423
M. Milen et al.
Cluster
Synlett
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-d6): 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
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.
(16) General Procedure for the Preparation of 1-Aryl-3H-pyr-
rolo[2,1-d][1,2,5]triazepine-4(5H)-thiones – Preparation of
Compounds 14a–i
(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
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-pyr-
rolo[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.
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 reac-
tion 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.
1-(4-Fluorophenyl)-3H-pyrrolo[2,1-d][1,2,5]triazepine-
4(5H)-thione (14a)
6-(4-Fluorophenyl)-2-phenyl-11H-imidazo[1,2-b]pyr-
rolo[1,2-e][1,2,5]triazepine (13a)
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-d6): 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-d6): 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.
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. 13
C
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.
1-Phenyl-3H-pyrrolo[2,1-d][1,2,5]triazepine-4(5H)-thione
(14f)
2-(4-Chlorophenyl)-6-(4-nitrophenyl)-11H-imidazo[1,2-
b]pyrrolo[1,2-e][1,2,5]triazepine (13h)
Yield 0.59 g (79%), yellow crystals, mp 229–230 °C (decomp.,
MeCN). IR (KBr): 3184, 1387, 1110, 703 cm–1 1H NMR (500
.
Yield 0.19 g (43%), yellow crystals, mp 283–284 °C (MeCN). IR
MHz, DMSO-d6): 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, J1
= 2.6 Hz, J2 = 4.0 Hz, 1 H), 6.28 (dd, J1 = 1.5 Hz, J2 = 3.8 Hz, 1 H),
5.11 (s, 2 H) ppm. 13C NMR (125 MHz, DMSO-d6): 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-Unsubsti-
tuted/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 disap-
peared 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 evapo-
rated. The crude material was purified by flash chromatogra-
phy.
(KBr): 1562, 1520, 1410, 1352, 727 cm–1 1H NMR (400 MHz,
.
DMSO-d6): 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-d6): 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 chromatog-
raphy 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-d6): 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-d6): 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,
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-d6): 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-d6): δ = 164.0 (d,
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 2418–2424