Novel approach to the synthesis of 6,7-dihydroquinazolino[3,2-a]- [1,5]benzodiazepin-13(15)-ones

Full text of DOI:10.1007/s10593-011-0772-6

Chemistry of Heterocyclic Compounds, Vol. 47, No. 3, May, 2011 (Russian Original Vol. 47, No. 3, March, 2011)
NOVEL APPROACH TO THE SYNTHESIS
OF 6,7-DIHYDROQUINAZOLINO[3,2-a]-
[1,5]BENZODIAZEPIN-13(15)-ONES
R. Janciene1*
Keywords: 5-acetyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one, o-nitrobenzoyl chloride, reductive
cyclization.
The quinazolin-4-one and 1,4-benzodiazepine structural fragments are frequently met in many natural
alkaloids [1-3]. In this work we propose a method for the design of the condensed system based on 2,3,4,5-
tetrahydro-2H-1,5-benzodiazepin-2-one. Acylation of the 5-acetylbenzodiazepin-2-ones 1a,b (5 mmol) by
o-nitrobenzoyl chloride (0.8 ml, 6 mmol) in a solution of dichloroethane in the presence of triethylamine (0.84
ml, 6 mmol) and a catalytic amount of 4-dimethylaminopyridine (DMAP) gave the 1-(2-nitrobenzoyl)amides
2a,b. Catalytic hydrogenation of the nitro group in compounds 2a,b in the presence of skeletal nickel catalyst
caused a reductive cyclization leading to the previously unknown 5-acetyl-6,7-dihydroquinazolino[3,2-a][1,5]-
benzodiazepin-13(5H)-ones 3a,b. The structure of the synthesized compounds was confirmed by their
spectroscopic data.
O2N
O
H
N
NO2
NEt3,
DMAP
O
H2, Ni
O
+
O
R
N
R
N
N
N
N
COCl
N
R
MeOC
2a,b
1a,b
MeOC
MeOC
3a,b
1-3 a R = H, b = Me
IR spectra were obtained on a Perkin-Elmer GX FTIR spectrometer using KBr tablets. 1H and 13C NMR
spectra were taken on a Varian Unity Inova 300 instrument (300 and 75 MHz respectively) using CDCl3 with
TMS as internal standard. Compounds 2a,b and 3a,b were purified chromatographically with subsequent
recrystallization from a mixture of ether and chloroform.
_______
* To whom correspondence should be addressed, e-mail: regina.janciene@bchi.vu.lt.
1 Institute of Biochemistry, Vilnius University, 12 Mokslininku St., Vilnius 08662, Lithuania.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 469-471, March, 2011. Original
article submitted February 25, 2011.
390
0009-3122/11/4703-0390©2011 Springer Science+Business Media, Inc.

5-Acetyl-1-(2-nitrobenzoyl)-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one (2a). Yield 1.3 g (74%);
mp 199-201ºC. IR spectrum, , cm-1: 1742, 1684, 1663 (CO); 1533, 1316 (NO2). 1H NMR spectrum, , ppm (J,
Hz): 2.04 (3H, s, COCH3); 2.39 (1H, m, 3-CH2); 2.59 (1H, m, 3-CH2); 3.38 (1H, m, 4-CH2); 4.90 (1H, m,
4-CH2); 7.31 (1H, dd, J = 1.3 and J = 7.6, H Ar); 7.38 (1H, dd, J = 1.5 and J = 7.5, H Ar); 7.54-7.66 (3H, m,
H Ar); 7.74-7.80 (2H, m, H Ar); 8.29 (1H, br. d, H Ar). 13C NMR spectrum, , ppm: 22.73 (COCH3); 35.23
(С-3); 45.04 (С-4); 124.25; 126.56; 129.14; 129.41; 129.51; 129.73; 130.17; 134.52; 134.60; 135.18; 135.81;
144.50 (С-2'); 167.51 (NСО); 170.50 (2-СО); 170.79 (СOCH3). Found, %: C 61.41; H 4.21; N 11.67.
C18H15N3O5. Calculated, %: C 61.19; H 4.28; N 11.89.
5-Acetyl-4-methyl-1-(2-nitrobenzoyl)-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one (2b). Yield
0.7 g (53%) based on the amount of reacted compound 1b (0.3 g recovered from the reaction mixture). Mp
1
205-207ºC. IR spectrum,  , cm-1: 1743, 1686, 1666 (CO); 1531, 1321 (NO2). H NMR spectrum, , ppm (J,
Hz): 1.02 (3H, d, J = 6.4, 4-CH3); 1.85 (3H, s, COCH3); 2.14 (1H, dd, J = 12.2 and J = 13.1, 3-CH2); 2.22 (1H,
dd, J = 5.3 and J = 13.1, 3-CH2); 5.08 (1H, m, 4-CH); 7.21 (1H, dd, J = 1.4 and J = 7.7, H Ar); 7.22 (1H, dd,
J = 1.3 and J = 7.5, H Ar); 7.46 (1H, dt, J = 1.7 and J = 7.6, H Ar); 7.51 (1H, dt, J = 1.4 and J = 7.6, H Ar); 7.52
(1H, dt, J = 1.5 and J = 7.5, H Ar); 7.63 (1H, dd, J = 1.8 and J = 7.6, H Ar); 7.66 (1H, dt, J = 1.2 and J = 7.5,
H Ar); 8.14 (1H, dd, J = 1.1 and J = 8.3, H Ar). 13C NMR spectrum (CDCl3 + 10% CD3OD), , ppm: 18.49
(4-CH3); 22.57 (COCH3); 42.11 (С-3); 51.27 (С-4); 123.91; 126.14; 129.00; 129.14; 129.41; 129.53; 130.22;
133.57; 134.31; 135.09; 144.08 (C-2'); 167.28 (NСО); 169.27 (2-СО); 170.20 (COCH3). Found, %: C 62.29;
H 4.72; N 11.23. C19H17N3O5. Calculated, %: C 62.12; H 4.66; N 11.44.
5-Acetyl-6,7-dihydroquinazolino[3,2-a][1,5]-benzodiazepin-13(5H)-one (3a). Yield 57%; mp
1
218-220ºC. IR spectrum, , cm-1: 1693, 1664 (CO); 1611 (C=N). H NMR spectrum, , ppm (J, Hz): 1.87 (3H,
s, COCH3); 2.75 (1H, m, 7-CH2); 3.10 (1H, m, 7-CH2); 3.49 (1H, m, 6-CH2); 4.94 (1H, m, 6-CH2); 7.35 (1H, m,
H Ar); 7.48-7.61 (3H, m, H Ar); 7.69 (2H, m, H Ar); 7.80 (1H, dt, J = 1.4 and J = 8.3, H Ar); 8.30 (1H, dd,
J = 1.3 and J = 8.0, H Ar). 13C NMR spectrum, , ppm: 22.79 (COCH3); 34.11 (С-7); 47.48 (С-6); 120.91;
127.14; 127.27; 129.06; 129.10; 130.00; 134.03; 134.89; 135.37; 146.95; 153.67 (С-7a); 160.77 (13-СО);
170.44 (COCH3). Found, %: C 70.58; H 4.90; N 13.91. C18H15N3O2. Calculated, %: C 70.81; H 4.95; N 13.76.
5-Acetyl-6-methyl-6,7-dihydroquinazolino[3,2-a][1,5]benzodiazepin-13(5H)-one (3b). Yield 55%;
1
mp 246-249ºC. IR spectrum, , cm-1: 1689, 1655 (CO); 1610 (C=N). H NMR spectrum, , ppm (J, Hz): 1.21
(3H, d, J = 6.3, 6-CH3); 1.81 (3H, s, COCH3); 2.40 (1H, dd, J = 12.4 and J = 13.6, 7-CH2); 2.97 (1H, dd, J = 5.0
and J = 13.7, 7-CH2); 5.25 (1H, m, 6-CH); 7.29 (1H, m, H Ar); 7.47-7.62 (3H, m, H Ar); 7.69 (2H, m, H Ar);
7.79 (1H, dt, J = 1.5 and J = 8.0, H Ar); 8.28 (1H, dd, J = 1.3 and J = 8.0, H Ar); 13C NMR spectrum, , ppm:
18.49 (6-CH3); 22.96 (COCH3); 41.32 (С-7); 54.00 (С-6); 120.83; 127.08; 127.11; 127.27; 128.98; 129.06;
129.62; 130.37; 133.47; 134.23; 134.88; 146.87; 153.50 (С-7a); 160.73 (13-СО); 169.68 (COCH3). Found, %:
C 71.68; H 5.45; N 31.01. C19H17N3O2. Calculated, %: C 71.46; H 5.37; N 13.16.
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