One-pot synthesis of 1-alkyl- 4,5-dihydro-6H-pyrrolo[1,2-a]- [1,4]benzodiazepin-6-one

Full text of DOI:10.1007/s10593-009-0393-5

Chemistry of Heterocyclic Compounds, Vol. 45, No. 9, 2009
ONE-POT SYNTHESIS OF 1-ALKYL-
4,5-DIHYDRO-6H-PYRROLO[1,2-a]-
[1,4]BENZODIAZEPIN-6-ONE
T. A. Stroganova1* and V. K. Vasilin1
Keywords: pyrrolo[1,2-a][1,4]benzodiazepine, furan, recyclization, one-pot synthesis.
Annelated derivatives of [1,4]diazepine are well known due to the broad range of their biological
activity. We have recently reported a synthesis of derivatives of pyrrolo[1,2-a][1,4]diazepine based on the acid-
catalyzed recyclization of N-(5-methyl-2-furyl)-3-aminothieno[2,3-b]pyridinecarboxamides and N-(5-methyl-
2-furyl)anthranilamides [1, 2]. This method involves the simultaneous formation of diazepine and pyrrole rings.
The anthranilamides used in the reaction were obtained by the reduction of the corresponding
ortho-nitrobenzamides.
In the present work, we present a one-pot synthesis of pyrrolo[1,2-a][1,4]benzodiazepinones 1a-c
directly from o-[N-(5-alkyl-2-furyl)methyl]nitrobenzamides 2a-c.
The proposed method involves opening of the furan ring to form a 1,4-diketone and followed by
reduction of the nitro group, leading to spontaneous intramolecular cyclization and formation of the
pyrrolodiazepine system.
O
O
+
+
N
–
–
R
R
N
O
R
R
O
O
HCl/EtOH
55–65°C
H
N
1
1
H
N
R
R
O
O
O
O
2a–c
1
R
SnCl2·2H2O,
~20°C
N
R
R
N
H
O
1a–c
1,2 a R = H; R1 = Me; b R =MeO, R1=Me; c R = MeO, R1=Et
_______
* To whom correspondence should be addressed, e-mail: tatka_s@mail.ru, e-mail: vasvk@mail.ru.
1Kuban State University of Technology, Krasnodar 350072, Russia.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1433-1435, September, 2009.
Original article submitted June 5, 2009.
0009-3122/09/4509-1151©2009 Springer Science+Business Media, Inc.
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The 1H NMR spectra were taken on a Bruker AM-300 spectrometer at 300 MHz in DMSO-d6 with TMS
as the internal standard. The electron impact mass spectra were taken on a MAT-112 mass spectrometer with
direct inlet into the ion source. The ionizing energy was 70 eV.
Synthesis of Compounds 1a-c (General Method). Solution of gaseous hydrogen chloride in ethanol
(20 ml) was added to a solution of nitroamide 2a-c (5 mmol) in ethanol (20 ml) and the mixture obtained was
maintained at 55-60°C until the starting reagent was completely consumed as indicated by thin-layer
chromatographic monitoring. Then, SnCl2·2H2O (4.5 g, 20 mmol) was added to the reaction mixture and the
suspension was stirred at room temperature for 10-14 h. The reaction mixture was diluted by adding 20-40 ml
ethyl acetate. The precipitate was separated by filtration. The filtrate was evaporated and the residue was
recrystallized from a mixture of ethyl acetate and petroleum ether.
1-Methyl-4,5-dihydro-6H-pyrrolo[1,2-a][1,4]benzodiazepine (1a) was obtained in 49% yield;
mp 230-231°C (mp 230-231°C [2]). The 1H NMR spectrum and mass spectrum were identical to those presented
in our previous work [2].
8,9-Dimethoxy-1-methyl-4,5-dihydro-6H-pyrrolo[1,2-a][1,4]benzodiazepine (1b) was obtained in
50% yield; mp 195-196°C (mp 195-196°C [1]). The 1H NMR spectrum and the mass spectrum were identical to
those presented in our previous work [1].
1-Ethyl-8,9-dimethoxy-4,5-dihydro-6H-pyrrolo[1,2-a][1,4]benzodiazepine (1c) was obtained in
1
54% yield; mp 110-112°C. H NMR spectrum, δ, ppm (J, Hz): 1.07 (3H, t, J = 7.6, CH2CH3); 2.84 (2H, q,
J = 7.6, CH2CH3); 3.82 (3H, s, OCH3); 3.85 (3H, s, OCH3); 3.90-4.07 (2H, m, CH2NH); 5.96 (1H, d, J = 3.2,
H pyrrole); 6.01 (1H, d, J = 3.2, H pyrrole); 6.92 (1H, s, H arom.); 7.26 (1H, s, H arom.); 8.40 (1H, br. s, NH).
Mass spectrum, m/z (Irel, %): 286 [M]+ (100), 285 (10), 271 (19), 258 (10), 257 (80), 244 (12), 243 (18), 242
(73), 228 (31), 214 (12), 198 (20), 197 (16), 184 (29), 170 (12), 168 (10), 165 (14), 156 (13), 141 (16), 79 (10),
44 (17), 43 (31). Found, %: C 67.18; H 6.24; N 9.69. C16H18N2O3. Calculated, %: C 67.12; H 6.34; N 9.78.
REFERENCES
1.
2.
T. A. Stroganova, A. V. Butin, V. K. Vasilin, T. A. Nevolina, and G. D. Krapivin, Synlett, 1106 (2007).
T. A. Stroganova, V. K. Vasilin, E. A. Zelenskaya, V. M. Red'kin, and G. D. Krapivin, Synthesis, 19,
3088 (2008).
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