486 Letters in Drug Design & Discovery, 2016, Vol. 13, No. 6
Lucescu et al.
Dimethyl 3-(4-bromobenzoyl)pyrrolo[2,1-a]quinoline-1,2-
dicarboxylate (9e)
(CDCl3, 400 MHz): ꢁ (ppm) 7.33 (d, J = 7.6 Hz, 1H, ArH),
7.56 (s, 1H, ArH), 7.67-7.77 (m, 6H, ArH), 7.82-7.87 (m,
1H, ArH), 8.98-9.03 (m, 1H, ArH), 9.55 (d, J = 7.6 Hz, 1H,
ArH). 13C NMR (CDCl3, 100 MHz): ꢀ 86.1 (C), 116.0 (CH),
116.9 (C), 123.6 (C), 124.1 (CH), 124.1 (C), 125.1 (CH),
127.3 (C), 127.3 (CH), 128.8 (CH), 129.0 (CH), 129.9 (C),
130.2 (CH), 130.6 (2CH), 131.9 (2CH), 137.8 (C), 138.1
(C), 184.3 (C).Anal. calcd for C20H11BrN2O: C, 64.02; H,
2.95; N, 7.47. Found: C, 64.71; H, 3.62; N, 7.69.
The general procedure was followed using 1-[2-(4-
bromophenyl)-2-oxoethyl]quinolinium bromide 3f (1.0 g,
2.46 mmol, 1 equiv), DMAD (0.39 mL, 3.19 mmol, 1.3
equiv), triethylamine (0.51 mL, 3.69 mmol, 1.5 equiv) and
acetonitrile (20 mL) to provide pure indolizine 9e as a cream
solid with the same physico-chemical properties as described
in the literature [24]; 22% yield;mp (EtOH) 193-196oC.
2a-(4-Bromobenzoyl)-6-methoxy-1,2,2a,3,4,4a,5,7a-octahy-
dropyrrolo[2,1,5-cd]indolizine-1,4-dicarbonitrile (12)
Dimethyl
1-(4-bromobenzoyl)-1,3a-dihydropyrrolo[1,2-
a]quinolone-2,3-dicarboxylate (11a)
The general procedure was followed using 1-[2-(4-
bromophenyl)-2-oxoethyl]-4-methoxypyridinium bromide 3e
(0.4 g, 1.0 mmol, 1 equiv), acrylonitrile (0.09 mL, 1.34
mmol, 1.3 equiv), triethylamine (0.22 mL, 1.55 mmol, 1.5
equiv) and acetonitrile (15 mL). White crystals; 12% yield;
mp (EtOH) 268-269oC. IR ꢀ cm-1: 2942, 2910, 2325, 2235,
1678, 1663, 1583, 1566, 1462, 1395, 1367, 1309, 1279,
1218, 1160, 1134, 1071, 1035, 993, 971, 851, 830, 808, 761,
By-product from the synthesis of indolizine 9e; yellow
solid; 44% yield; mp (EtOH) 121-125oC. IR ꢀ cm-1: 1733,
1695, 1678, 1625, 1583, 1556, 1470, 1426, 1353, 1250,
1067, 1009, 771, 760. 1H NMR (CDCl3, 400 MHz): ꢁ (ppm)
3.49 (s, 3H, CH3), 3.90 (s, 3H, CH3), 4.56 (d, J = 12.8 Hz,
1H, CH), 5.44 (d, J = 12.8 Hz, 1H, CH), 5.80 (d, J = 6.8 Hz,
1H, ArH), 6.22 (d, J = 6.8 Hz, 1H, ArH), 7.04 (s, 1H, ArH),
7.26 (s, 1H, ArH), 7.36 (s, 1H, ArH), 7.52-7.55 (m, 3H,
ArH), 7.86 (d, J = 6.8 Hz, 2H, ArH). 13C NMR (CDCl3, 100
MHz): ꢀ 51.3 (CH3), 53.0 (CH3), 53.2 (CH), 65.4 (CH),
104.2 (C), 109.4 (CH), 123.6 (CH), 123.7 (CH), 124.8 (CH),
127.3 (CH), 128.4 (CH), 130.0 (C), 130.4 (C), 130.6 (2CH),
131.4 (C), 132.6 (2CH), 133.7 (C), 150.5 (C), 164.2 (C),
173.8 (C), 188.1 (C). Anal. calcd for C23H18BrNO5: C, 58.99;
H, 3.87; N, 2.99. Found: C, 59,23; H, 4.47; N, 3.26.
1
722, 664, 578, 466. H NMR (CDCl3, 400 MHz): ꢁ (ppm)
2.31-2.42 (m, 2H, CH2), 2.60-2.65 (m, 1H, CH), 2.72-2.82
(m, 2H, CH2), 3.18-3.24 (m, 1H, CH), 3.34-3.4 (m, 3H,
CH2CH), 3.65 (s, 3H, OCH3), 3.92-3.96 (m, 1H, CH), 4.71-
4.72 (m, 1H, CH), 7.61 (d, J = 9.2 Hz, 2H, ArH), 8.10 (d, J =
8.4 Hz, 2H, ArH). 13C NMR (CDCl3, 100 MHz): ꢀ 31.9
(CH2), 32.7 (CH), 34.5 (CH), 39.5 (CH2), 40.7 (CH2), 55.3
(CH3), 58.7 (CH), 59.9 (CH), 79.3 (C), 90.1 (CH), 118.9 (C),
121.3 (C), 128.8 (C), 131.4 (2CH), 131.9 (2CH), 132.8 (C),
157.0 (C), 198.2 (C). Anal. calcd for C20H18BrN3O2: C,
58.26; H, 4.40; N, 10.19. Found: C, 59.12; H, 4.72; N, 10.64.
3-(4-Bromobenzoyl)pyrrolo[2,1-a]quinoline-1-carbonitrile
(10a)
The general procedure was followed using 1-[2-(4-
bromophenyl)-2-oxoethyl]quinolinium bromide 3f (0.7 g,
1.72 mmol, 1 equiv), acrylonitrile (0.14 mL, 2.24 mmol, 1.3
equiv), triethylamine (0.36 mL, 2.58 mmol, 1.5 equiv) and
acetonitrile (15 mL). Cream solid; 14% yield; mp (EtOH)
282-284oC. IR ꢀ cm-1: 3126, 2225, 1626, 1588, 1535, 1467,
1423, 1324, 1235, 1170, 1069, 1010, 968, 879, 833, 801,
General Procedure for the Preparation of 3-(4-substituted
benzoyl)indolizine-1-carboxylic acids 7a and 7b
Aqueous 2N NaOH was added to a suspension of ethyl
ester 6c and 6f (1 equiv) in MeOH. The reaction mixture was
stirred at reflux, until complete solubilization. The resulting
mixture was cooled to room temperature, and then citric acid
was added until complete precipitation. The carboxylic acid
obtained 7a and 7b was washed with hot ethanol and col-
lected by filtration.
1
749, 737, 685, 562, 504, 466, 408. H NMR (CDCl3, 400
MHz): ꢁ (ppm) 7.26 (d, J = 7.6 Hz, 1H, ArH), 7.60 (s, 1H,
ArH), 7.69 (d, J = 8.8 Hz, 2H, ArH), 7.72 (d, J = 8.8 Hz, 2H,
ArH), 7.74-7.77 (m, 2H, ArH), 7.83-7.86 (m, 1H, ArH), 9.01
(d, J = 7.2Hz, 1H, ArH), 9.46 (d, J = 7.2 Hz, 1H, ArH). 13C
NMR (CDCl3, 100 MHz): ꢀ 103.0 (C), 115.6 (CH), 117.3
(C), 120.6 (CH), 124.5 (C), 125.3 (CH), 126.7 (C), 127.0
(CH), 128.5 (C), 128.9 (CH), 129.9 (CH), 130.9 (C), 131.2
(2CH), 131.9 (2CH), 134.1 (C), 136.4 (CH), 137.4 (C),
179.2 (C). Anal. calcd for C20H11BrN2O: C, 64.02; H, 2.95;
N, 7.47. Found: C, 64.61; H, 3.56; N, 7.84.
3-(4-Bromobenzoyl)indolizine-1-carboxylic acid (7a)
The general procedure was followed using ethyl 3-(4-
bromobenzoyl)-7-methylindolizine-1-carboxylate 6c (0.1 g,
0.28 mmol, 1 equiv), NaOHaq 2N (4 mL) and MeOH (4 mL)
to provide pure carboxylic acid 7a as a white solid with the
same physico-chemical properties as described in the litera-
ture [20]; 76% yield; mp (EtOH) 275-277oC.
3-(4-Bromobenzoyl)pyrrolo[2,1-a]isoquinoline-1-carbonit-
rile (10b)
3-(4-Bromobenzoyl)pyrrolo[1,2-a]quinoline-1-carboxylic
acid (7b)
The general procedure was followed using 2-[2-(4-
bromophenyl)-2-oxoethyl]isoquinolinium bromide 3g (0.7 g,
1.72 mmol, 1 equiv), acrylonitrile (0.14 mL, 2.24 mmol, 1.3
equiv), triethylamine (0.36 mL, 2.58 mmol, 1.5 equiv) and
acetonitrile (15 mL). Cream solid; 11% yield; mp (EtOH)
282-285oC. IR ꢀ cm-1: 3127, 2225, 1626, 1588, 1535, 1467,
1452, 1423, 1362, 1342, 1236, 1171, 1069, 1010, 968, 879,
833, 801, 776, 749, 737, 685, 562, 467, 408. 1H NMR
The general procedure was followed using ethyl 1-(4-
bromobenzoyl)pyrrolo[1,2-a]quinoline-3-carboxylate 6f (0.1
g, 0.25 mmol, 1 equiv), NaOHaq 2N (4 mL) and MeOH (4
mL). White solid; 97% yield; mp (EtOH) 267-269oC. IR ꢀ
cm-1: 3150, 1692, 1621, 1589, 1518, 1459, 1356, 1338, 1238,
1195, 1159, 1140, 965, 870, 748.1H NMR (DMSO-d6, 400