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Synlett 2007(7): 1106-1108  
DOI: 10.1055/s-2007-977430
LETTER
© Georg Thieme Verlag Stuttgart · New York

A New Strategy for Pyrrolo[1,2-a][1,4]diazepine Structure Formation

Tatyana A. Stroganova, Alexander V. Butin*, Vladimir K. Vasilin, Tatyana A. Nevolina, Gennady D. Krapivin
Research Institute of Heterocyclic Compounds Chemistry, Kuban State University of Technology, Moskovskaya st. 2, Krasnodar 350072, Russian Federation
Fax: +7(861)2596592; e-Mail: alexander_butin@mail.ru;
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Publikationsverlauf

Received 20 October 2006
Publikationsdatum:
13. April 2007 (online)

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Abstract

A new method is elaborated for the synthesis of benzo- and thieno[2,3-b]pyrido-annelated pyrrolo[1,2-a][1,4]diazepine skeleton, as a result of recyclization of furfuryl amides of the corresponding aromatic and heteroaromatic acids with an amino group in the ortho position. A feature of the method is a simultaneous formation of pyrrole and diazepine rings in the reaction.

Key words

furan - ring opening - ring closure - pyrrolo[1,2-a][1,4]diazepinone

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15

General Procedure for the Preparation of Compounds 2a,b To a stirred solution of 5-methylfurfurylamine (12 mmol) in anhyd benzene (30 mL) a solution of 2-nitrobenzoyl or 2-nitroveratroyl chloride (10 mmol) in benzene (30 mL) was added dropwise over 30 min. The reaction mixture was agitated at r.t. for an additional 1 h and then cold sat. aq Na2CO3 (50 mL) was added. The organic layer was separated, washed with H2O, dried over Na2SO4 and concentrated in vacuo. The residue was crystallized from PE-CH2Cl2.
Selected analytical data for 2b: mp 166-167 °C. IR: νmax = 3260, 1642, 1580, 1519, 1339, 1289, 1267, 1226, 1052, 994, 872, 789 cm-1. 1H NMR (300 MHz, CDCl3): δ = 2.28 (s, 3 H, CH3), 3.96 (s, 3 H, OCH3), 3.97 (s, 3 H, OCH3), 4.58 (d, 2 H, J = 5.3 Hz, CH2), 5.85 (d, 1 H, J = 3.0 Hz, HFur), 5.98 (br s, 1 H, NH), 6.22 (d, 1 H, J = 3.0 Hz, HFur), 6.91 (s, 1 H, HAr), 7.90 (s, 1 H, HAr). MS: m/z (%) = 302 (10) [M+ - 18], 215 (22), 194 (58), 181 (22), 164 (49), 150 (13), 136 (76), 110 (100), 95 (96). Anal. Calcd for C15H16N2O6: C, 56.25; H, 5.03; N, 8.75. Found: C, 56.12; H, 5.09; N, 8.80.

16

General Procedure for the Preparation of Compounds 3a,b A mixture of amide 2a,b (4.3 mmol), hydrazine hydrate (1.5 mL) and activated Raney nickel (1.0 g) in EtOH (60 mL) was refluxed for 10-20 min until complete conversion of 2a,b (TLC). The mixture was filtered, and the filtrate was evaporated to dryness under reduced pressure. The residue was decolorized with charcoal in EtOAc-PE solution. The solvent was removed in vacuo and the resulting product was recrystallized from PE-CH2Cl2 to afford amino amides 3a,b.
Selected analytical data for 3b: mp 125-126 °C. IR: νmax = 3373, 3293, 1629, 1592, 1535, 1509, 1453, 1361, 1262, 1209, 1171, 1104, 1024, 887, 829, 780 cm-1. 1H NMR (300 MHz, CDCl3): δ = 2.29 (s, 3 H, CH3), 3.82 (s, 3 H, OCH3), 3.86 (s, 3 H, OCH3), 4.53 (d, 2 H, J = 5.3 Hz, CH2), 5.42 (br s, 2 H, NH2), 5.92 (d, 1 H, J = 3.0 Hz, HFur), 6.17 (d, 1 H, J = 3.0 Hz, HFur), 6.19 (br s, 2 H, NH + HAr), 6.82 (s, 1 H, HAr). MS: m/z (%) = 290 (9) [M+], 180 (22), 110 (89), 95 (100). Anal. Calcd for C15H18N2O4: C, 62.06; H, 6.25; N, 9.65. Found: C, 62.14; H, 6.19; N, 9.60.

17

General Procedure for the Preparation of Compounds 5a,b A mixture of amino amide 3a,b (2 mmol), glacial AcOH (10 mL) and concd HCl (1.5 mL) was kept at 60-70 °C until complete conversion of the initial compounds (TLC). The reaction mixture was poured into iced H2O (100 mL) and neutralized with NaHCO3 to approximately pH 7. The precipitate thus obtained was filtered off, washed with H2O, air-dried and dissolved in EtOAc-PE. The solution was passed through a pad of silica gel and left for crystallization.
Selected analytical data for 5b: mp 195-196 °C. IR: νmax = 3189, 1652, 1609, 1514, 1458, 1256, 1213, 1127, 1040, 1017, 926, 872, 799 cm-1. 1H NMR (300 MHz, CDCl3): δ = 2.34 (s, 3 H, CH3), 3.93 (s, 3 H, OCH3), 3.96 (s, 3 H, OCH3), 4.08-4.13 (m, 2 H, CH2), 5.99 (d, 1 H, J = 3.2 Hz, HPyr), 6.02 (d, 1 H, J = 3.2 Hz, HPyr), 6.77 (s, 1 H, HAr), 7.01 (br s, 1 H, NH), 7.44 (s, 1 H, HAr). 13C NMR (50 MHz, CDCl3): δ = 14.4, 38.2, 56.2, 104.6, 108.2, 109.5, 112.8, 121.4, 129.1, 130.1, 132.9, 147.2, 151.1, 170.3. MS: m/z (%) = 272 (100) [M+], 257 (30), 244 (16), 243 (57), 229 (24), 228 (66), 200(16), 198 (15), 185 (12), 172 (14), 170 (14), 165 (33), 122 (19). Anal. Calcd for C15H16N2O3: C, 66.16; H, 5.92; N, 10.29. Found: C, 66.10; H, 5.99; N, 10.23.

18

General Procedure for the Preparation of Compounds 7a-c To a suspension of pyridinethione 6 (10 mmol) in EtOH (75 mL) KOH (10 mmol, 10% aq soln) was added and the reaction mixture was heated until the complete dissolution of 6. Chloroacetamide was added and, after 15 min, the mixture was treated with a further portion of KOH (10 mmol, 10% aq soln). The solution thus obtained was allowed to stand for 2 h at r.t. The mixture was quenched with H2O (25 mL) and the precipitate formed was separated by filtration. The crystals were dried and recrystallized from EtOH-DMF (10:3).
Selected analytical data for 7c: mp 77-78 °C. IR: νmax = 3404, 3313, 3241, 1657, 1594, 1544, 1501, 1417, 1305, 1294, 1269, 1218, 1198, 1186, 1155, 1088, 1071, 1016, 918, 865, 799, 752, 705 cm-1. 1H NMR (300 MHz, CDCl3): δ = 2.24 (s, 3 H, CH3), 2.57 (s, 3 H, CH3), 3.38 (s, 3 H, OCH3), 4.34 (d, 2 H, J = 5.2 Hz, CH2Fur), 4.83 (s, 2 H, CH 2OCH3), 5.98 (d, 1 H, J = 3.0 Hz, HFur), 6.10 (d, 1 H, J = 3.0 Hz, HFur), 6.91 (br s, 2 H, NH2), 7.24 (s, 1 H, CHPy), 8.13 (t, J = 5.2 Hz, NH). MS: m/z (%) = 345 (51) [M+], 235 (33), 219 (16), 208 (10), 204 (11), 175 (10), 110 (69), 96 (12), 95 (100). Anal. Calcd for C17H19N3O3S: C, 59.11; H, 5.54; N, 12.17. Found: C, 59.17; H, 5.49; N, 12.21.

20

Compounds 8a-c were prepared from 6a-c similarly to 5a,b (see ref. 17).
Selected analytical data for compound 8c: mp 240-241 °C. IR: νmax = 3168, 1640, 1584, 1549, 1527, 1517, 1345, 1267, 1255, 1213, 1198, 1155, 1109, 942, 859, 804, 777, 752 cm-1. 1H NMR (300 MHz, DMSO-d 6): δ = 1.93 (s, 3 H, CH3), 2.65 (s, 3 H, CH3), 3.23 (s, 3 H, OCH3), 4.13 (d, J = 13.2 Hz, 1 H, CH2), 4.15 (d, J = 5.2 Hz, 2 H, CH2), 4.48 (d, J = 13.2 Hz, 1 H, CH2), 6.10 (s, 2 H, HPyr), 7.45 (s, 1 H, HPy), 8.72 (t, J = 5.2 Hz, NH). 13C NMR (50 MHz, CDCl3): δ = 13.1, 24.0, 37.7, 58.2, 69.0, 105.7, 109.8, 120.0, 123.4, 128.3, 129.3, 129.6, 134.4, 144.1, 158.2, 158.7, 163.5. MS: m/z (%) = 327 (100) [M+], 312 (11), 284 (10), 283 (84), 280 (32), 268 (18), 267 (14), 266 (20), 253 (18), 240 (15), 239 (22), 238 (12), 225 (13), 218 (15), 217 (49), 190 (47), 189 (12), 149 (12), 133 (16). Anal. Calcd for C17H17N3O2S: C, 62.37; H, 5.23; N, 12.83. Found: C, 62.30; H, 5.29; N, 12.89.