964
T. A. Abdallah
Vol 44
spectrometer at 70 eV. Elemental analyses were carried out at
the Microanalytical Center of Cairo University, Giza, Egypt.
Compound 2 was previously described [6].
solid product was collected by filtration and crystallized from
acetic acid.
5-(1H-Indol-3-yl)[1,2,4]triazolo[1,5-a]pyrimidine-6-carbo-
nitrile (15). Yield (70%), mp 229-231°C; ir CN 2253, NH 3223
3-Dimethylamino-2-(1H-indole-3-carbonyl)-acrylonitrile (3).
A mixture of compound 2 [6] (1.8 g, 10 mmoles) and
dimethylformamide dimethylacetal (16 mmoles) was refluxed in
dioxan for 10 min. The reaction mixture was then cooled and the
solid formed was collected by filtration and crystallized from
ethanol, yield: (75%), mp 186-188°C; ir: CO 1700.9, CN
1
cm-1; H nmr (CDCl3): ꢀ 7.25 – 7.99 (m, 7H, Ar-protons), 8.39
ppm (s, 1H, NH) 13C-NMR: 102.30, 111.52, 112.36, 116.52,
121.02. 121.73, 122.43, 125.61, 131.03, 135.34, 149.06, 155.47,
157.96, 172.05; ms: m/z 259 (M+), 237, 183, 143, 115, 89, 58.
Anal. Calcd. for C14H8N6: C, 64.61; H, 3.10; N, 32.29. Found:
C, 64.67; H, 3.21; N, 32.14.
1
2195.5, NH 3302.5 cm–1; H nmr (CDCl3): ꢀ 3.27 (s, 3H, CH3),
(7-Amino-pyrazolo[1,5-a]pyrimidin-6-yl)-(1H-indol-3-yl)-
methanone (19). Yield (72%). mp 212-214°C; ir CO 1625, NH
3.33 (s, 3H, CH3), 3.87 (s, 1H, =CH), 7.17-8.28 (m, 5H, Ar-
protons), 8.41 ppm (s, 1H, NH); ms: m/z 239 (M+), 178, 222,
144, 116, 89. Anal. Calcd. for C14H13N3O: C, 70.28; H, 5.48; N,
17.56. Found: C, 70.23; H, 5.62; N, 17.47.
1
3121, NH2 3304, 3454 cm-1; H nmr (DMSO): ꢀ 6.57 (d, 1H,
pyrazole proton, J=12Hz), 7.19-7.27 (m, 2H, Ar- protons), 7.52
(d, 1H, pyrazole proton, J=12Hz), 8.10-8.17 (m, 2H, Ar-
protons), 8.26 (s, 1H, pyrimidine proton), 8.75 (s, 1H, Indole
protons), 8.78 (s, 2H, NH2), 12.08 ppm (s,1H, NH); ms: m/z
277 (M+), 260, 144, 117, 89. Anal. Calcd. for C15H11N5O: C,
64.98; H, 3.97; N, 25.27. Found: C, 64.92; H, 4.10; N, 25.45.
2-(1H-Indole-3-carbonyl)-3-(4-phenylthiazol-2-yl-amino)-
acrylonitrile (23). Yield (63%), mp 220-222°C; ir CO
3-(4-Chlorophenylamino)-2-(1H-indole-3-carbonyl)-acryl-
onitrile (5). A mixture of enamine 3 (1.0 g, 4 mmoles) and
4-chloroaniline (0.51 g, 4 mmoles) was refluxed in acetic
acid (10 ml) for 4 hrs. The solid product formed after
cooling was collected by filtration and crystallized from
ethanol, yield (60%), mp 234-236 °C; ir: CO 1778, CN
1
2207.2, (broad NH) 3245.6 cm-1; H nmr (CDCl3): ꢀ 7.1- 8.7
1
1639.8,CN 2210.1, broad NH 3221.3 cm-1; H nmr (CDCl3): ꢀ
(m, 9H, Ar protons), 8.86 (s, 1H, Indole proton), 12.90 (s,
1H, NH), 12.95 ppm (s, 1H, NH); ms: m/z 323 (M++2),
321(M+), 303, 144, 116, 89. Anal. Calcd. for C18H12N3ClO:
C, 67.19; H, 3.76; N, 13.06; Cl, 11.02. Found: C, 67.31; H,
3.63; N, 13.18; Cl, 10.93.
4.48 (s, 1H, CH) 7.09- 8.48 (m, 11H, Ar-protons), 8.37(s, 1H,
NH), 12.16 ppm (s,1H, NH); ms: m/z 370 (M+), 252, 195, 162,
117. Anal. Calcd. for C21H14N4OS: C, 68.09; H, 3.81; N,
15.12; S, 8.66. Found: C, 68.34; H, 3.65; N, 14.98; S, 8.49.
2-[2-Cyano-3(1H-indol-3-yl)-3-oxo-propenylamino]-4,5,
6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid ethyl
ester (24). Yield (64%), mp 268-270°C; ir CO 1697, 1794, CN
2196, broad NH 3383 cm-1; 1H nmr (CDCl3): ꢀ 1.50 (t, 3H, CH3,
J= 7.2 Hz), 1.52 (m, 4H, 2CH2), 2.67 (m , 2H, CH2), 2.82 (m ,
2H, CH2) 4.55(q, 2H, J= 7.2 Hz,), 7.26-8.54 (m, 5H, Ar -
protons), 8.62 (s, 1H, Indole proton), 13.98 (s, 1H, NH), 14.02
ppm (s, 1H, NH); 13 C nmr (DMSO) 14.23, 21.90, 22.35, 24.19,
26.01, 60.63, 84.05, 112.28, 113.82, 114.88, 120.88, 121.98,
123.17, 126.12, 126.48, 132.04, 133.96, 135.98, 148.70, 151.55,
162.72, 183.11; ms: m/z 419 (M+), 229, 144, 116, 89. Anal.
Calcd. for C23H21N3O3S: C, 65.69; H, 5.27; N, 9.99; S, 11.41.
Found: C, 65.82; H, 5.41; N, 9.94; S, 11.53.
3-(1H-Indol-3-yl)-1H-pyrazole-4-carbonitrile (6).
A
mixture of 3 (1.0 g, 4 mmoles) and hydrazine hydrate (5 ml) in
ethanol was refluxed for 3 hrs, then poured on cold water. The
solid product was collected by filtration and crystallized from
ethanol, yield (72%); mp 218-219 °C; ir: CN 2228.5, 2NH
1
3225.8, 3290.4 cm-1; H nmr (CDCl3): ꢀ 7.2-8.1 (m, 5H, Ar-
protons), 7.98(s, 1H, pyrazole H-5), 8.5 ppm (s, 2H, 2NH); ms:
m/z 208 (M+), 178, 153, 126, 62. Anal. Calcd. for C12H8N4: C,
69.22; H, 3.87; N, 26.91. Found: C, 69.31; H, 3.84; N, 26.14.
General procedure for the reaction of ethyl acetoacetate
or acetyl acetone with enamine (3). A mixture of enamine 3
(1.0 g, 4 mmoles) in acetic acid (10 ml) and the appropriate
active methylene compound (4 mmoles) in the presence of
ammonium acetate (6 mmoles) was refluxed for 6 hrs. The
mixture was cooled then the solid product was collected by
filtration and crystallized from acetic acid to give 10 and 12.
5-Cyano-6-(1H-indol-3-yl)-2-methyl-nicotinic acid ethyl
ester (10). Yield (67%), mp 238-40°C; ir: CO 1793.6, CN
4-(6,7-Dimethoxy-3,4-dihydroisoquinolin-1-yl)-2-(1H-indole-
3-carbonyl)-but-2-enenitrile (25). To a mixture of enamine 3
(1.0 g, 3.0 mmoles) in acetic acid (10 ml) was added (0.9 g, 3.0
mmoles) of 1-methyl-6,7-dimethoxyisoquinoline 22. The
mixture was refluxed for 7 hrs then cooled. The solid product
was collected by filtration and crystallized from dimethyl-
formamide, yield (76%), mp 290-292°C; ir CO 1634.6, CN
1
2254.2, NH 3222.8 cm-1; H nmr(CDCl3): ꢀ 1.47 (t, 3H, CH3, J=
7.2 Hz), 2.08 (s, 3H, CH3), 4.41(q, 2H, CH2, J= 7.2 Hz), 7.2-
8.5(m, 6H, Ar-protons), 8.76 ppm (s,1H, NH); ms:m/z 305 (M+),
184, 144, 89. Anal. Calcd. for C18H15N3O2: C, 70.81; H, 4.95;
N, 13.76. Found: C, 70.89; H, 4.72; N, 13.52.
1
2215.0, 2NH 3423.0, 3161.5 cm-1; H nmr (DMSO-d6):ꢀ 3.14
(m, 2H, CH2), 3.89 (s, 3H, OCH3), 3.93(s, 3H, OCH3), 4.90 (m,
2H, CH2), 7.16-8.10 (m, 7H, Ar-protons), 7.40 (d, 1H, CH
proton, J=12Hz), 8.07 (d, 1H, CH proton, J=12Hz), 8.92 (s, 1H,
1NH), 11.89 ppm (s, 1H, 1NH) ; ms: m/z 399 (M+), 382, 199.
Anal. Calcd. for C24H21N3O3: C, 72.16; H, 5.30; N, 10.52.
Found: C, 72.10; H, 5.51; N, 10.65.
4-Acetyl-2-(1H-indole-3-carbonyl)-5-oxohex-2-enenitrile (12).
Yield (62%), mp 243-245°C; ir: CO 1633.4, 1692.1, 1787.6.,
1
CN 2193.2, NH 3220.6 cm-1; H nmr (CDCl3): ꢀ 2.40 (s, 1H,
CH), 3.27 (s, 3H, CH3), 3.47 (s, 3H, CH3), 3.88 (s, 1H, =CH),
7.25-8.46 (m, 4H, Ar-protons), 8.54 (s, 1H, Indole proton), 8.87
ppm (s, 1H, NH); ms: m/z 294 (M+), 238, 221, 144, 115, 88, 62 .
Anal. Calcd. for C17H14N2O3: C, 69.38; H, 4.79; N, 9.52.
Found: C, 69.50; H, 4.68; N, 9.37.
General procedure for the reaction of 13, 17, 20, 21 with
enamine (3). To a solution of enamine 3 in acetic acid (10 ml)
was added the appropriate heterocyclic aromatic amines 13, 17,
20, 21 then the mixture was refluxed for 4 hrs. After cooling, the
REFERENCES
[1] Waldmann, H.; Braun, M.; Weqmann, M.; Gewehr, M.
Tetrahedron 1993, 49, 397.
[2] Addmann, R.; Schnetmann, E. G.; Frölich, R.; Saarenkelo,
P.; Holst, C. Chem. Eur. J 2001, 7, 711.
[3] Al-Saleh, B.; EL- Apasery, M. A.; Abdel- Aziz, R. S.;
Elnagdi, M. H. J. Heterocycl. Chem. 2005, 42, 563.