A novel and simple synthesis of 9H-pyrimido[4,5-b] indoles under microwave irradiation and solvent-free conditions

Article abstract of DOI:10.1055/s-2007-1000872

A novel synthesis of 9H-pyrimido[4,5-b]indoles is described from a simple microwave-assisted reaction between oxindoles and aryl nitriles under solvent-free conditions in good to excellent yields. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-1000872

LETTER
177
A Novel and Simple Synthesis of 9H-Pyrimido[4,5-b]indoles under Microwave
Irradiation and Solvent-Free Conditions
N
ovel and Simple Synt
e
hesis of
9
H
h
-Pyrimido[4
d
,5-
b
]indole
s
i Adib,*a Bagher Mohammadi,a Hamid Reza Bijanzadehb
a
School of Chemistry, University College of Science, University of Tehran, P.O. Box 14155-6455, Tehran, Iran
Fax +98(21)66495291; E-mail: madib@khayam.ut.ac.ir
b
Department of Chemistry, Tarbiat Modarres University, P.O. Box 14115-175, Tehran, Iran
Received 14 May 2007
thetic approaches involve: reaction of 2-ethoxy-3-ben-
zylidenindolenine tetrafluoroborate with amidines,
guanidine and thiourea,8 extension of the Nenitzescu reac-
tion,9 heteroannulation of 2-[bis(methylthio)methylene]-
1-methyl-3-oxoindole with b-substituted b-lithioami-
noacrylonitriles, malononitrile and guanidine,10 palladi-
um-catalyzed arylation of pyrimidine substrates,11
addition of glycine ethyl ester to 2,4,6-trichloropyrimi-
dine,12 aza-wittig-type reaction of bisiminophosphoranes
with aromatic isocyanates,13 cyclization of 4-
azidouracils14 and 6-(phenylhydrazino)uracils,15 and also
oxidation of the corresponding 5,6,7,8-tetrahydropyrimi-
do[4,5-b]indoles.16 Most of the reported synthetic meth-
ods suffer from disadvantages such as the use of volatile
organic solvents, unsatisfactory product yields and rela-
tively long reaction times. In addition, in some of these
methods the reactants such as 2,3-functionalized indoles,
b-substituted b-lithioaminoacrylonitriles, bisiminophos-
phoranes, or uracil derivatives have to be synthesized
first, hence these methods are relatively expensive and
time-consuming.
Abstract: A novel synthesis of 9H-pyrimido[4,5-b]indoles is de-
scribed from a simple microwave-assisted reaction between oxin-
doles and aryl nitriles under solvent-free conditions in good to
excellent yields.
Key words: 9H-pyrimido[4,5-b]indoles, oxindoles, aryl nitriles,
solvent-free synthesis, cyclizations, heterocycles
Pyrimido[4,5-b]indoles, fused tricyclic 6:5:6 compounds
with three nitrogen atoms (2:1:0; positions 1, 3, and 9, and
bicyclic 5:6 analogues, pyrrolo[2,3-d]pyrimidines), are of
interest because of their extensive use as active ingredi-
ents of pharmaceutical preparations.1,2 Recently some of
these compounds have been reported as useful new drugs
in treatment of myocardial injury, pulmonary hyperten-
sion, renal failure, Huntington’s chorea, as well as neuro-
degenerative disorders such as Parkinson’s disease,
Alzheimer’s disease and focal ischemia.2 Furthermore,
some examples have been used as A1 and A3 adenosine
receptor antagonists (Figure 1, 1),3 bronchodilators
(Figure 1, 2),4 blood platelet aggregation inhibitors,5 anti-
hypertensive agents,5 epidermal growth factor receptor ty-
rosine kinase (EGFRTK) inhibitors,2 mitogen-activated
protein kinase (MAPK) inhibitors,2 and antagonists at
CRF1 receptors.6
The application of microwave irradiation in organic syn-
thesis for conducting reactions at highly accelerated rates
is an emerging technique.17 In fact, in recent years, the use
of microwaves have become popular among synthetic or-
ganic chemists both to improve classical organic reactions
(shortening reaction times and/or improving yields) as
well as to promote new reactions.
H2N
O
N
N
R
Ph
As part of our ongoing program to develop new facile
methods for the preparation of biologically active hetero-
cyclic compounds from readily available building blocks,
we report herein a new facile method for the synthesis of
pyrimido[4,5-b]indoles. Thus, oxindoles 3 react with a
range of aryl nitriles 4 under microwave irradiation18 and
solvent-free conditions to produce 9H-pyrimido[4,5-b]in-
doles 5a–s in 69–85% yields (Scheme 1, Table 1).
N
N
N
N
H
O
Ph
Me
n-Pr
1, a potent A1 adenosine
2, R = MeS, NH2, MeNH
receptor antagonist
active bronchodilators
Figure 1 Examples of biologically active pyrimido[4,5-b]indoles.
So far, several synthetic methods have been reported for
the preparation of pyrimido[4,5-b]indole ring systems.
The most common synthetic routes involve ring closure of
2,3-functionalized indoles, e.g. 2-aminoindole-3-carbox-
ylates or 2-aminoindole-3-carbonitriles with CN atom
fragments such as formamide or cyanamide.2,7 Other syn-
Ar
X
X
N
sat. NaOH (cat.)
+
ArCN
O
Ar
MW, 180 °C,
4 min
N
N
N
R
R
5
3
4
SYNLETT 2008, No. 2, pp 0177–0180
x
x.
x
x.
2
0
0
7
Advanced online publication: 21.12.2007
DOI: 10.1055/s-2007-1000872; Art ID: D14607ST
Scheme 1
© Georg Thieme Verlag Stuttgart · New York

178
M. Adib et al.
LETTER
The reactions were carried out by first mixing the oxin-
dole and the nitrile. Then, a catalytic amount of saturated
aqueous NaOH solution was added and the reaction mix-
ture was irradiated in a microwave oven at 180 °C for four
minutes (progress of the reaction was followed by TLC
monitoring minute by minute). TLC and 1H NMR analy-
sis of the reaction mixtures clearly indicated the formation
of pyrimido[4,5-b]indole derivatives 5 in good to excel-
lent yields.19
Acknowledgment
This research was supported by the Research Council of University
of Tehran as a research project (6102036/1/02).
References and Notes
(1) Delia, T. J.; Hurst, D. T. In Comprehensive Heterocyclic
Chemistry II, Vol. 7; Katritzky, A. R.; Rees, C. W.; Scriven,
E. V. F., Eds.; Pergamon Press: London, 1996, Chap. 7, 229–
281; and references therein.
(2) Lowinger, T.; Shimazaki, M.; Sato, H.; Tanaka, K.; Tsuno,
N.; Marx, K.; Yamamoto, M.; Urbahns, K.; Gantner, F.;
Okigami, H.; Nakashima, K.; Takeshita, K.; Bacon, K. B.;
Komura, H.; Yoshida, N. PCT Int. Appl., WO03037898,
2003.
(3) Hess, S.; Muller, C. E.; Frobenius, W.; Reith, U.; Klotz, K.
N.; Eger, K. J. Med. Chem. 2000, 43, 4636.
(4) Coates, W. J. US Patent 5162316, 1992.
Table 1 Synthesis of 9H-Pyrimido[4,5-b]indoles 5a–s
5
a
b
c
d
e
f
R
X
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Br
Br
Br
Ar
Yield (%)a
80
H
Ph
H
2-MeC6H4
4-MeC6H4
4-MeOC6H4
3-O2NC6H4
4-O2NC6H4
4-FC6H4
2-ClC6H4
3-ClC6H4
4-ClC6H4
2-BrC6H4
3-BrC6H4
4-BrC6H4
Ph
74
H
78
(5) Monge, A.; Palop, J. A.; Goni, T.; Parrado, P.; Martinez, F.;
Fernandezalvarez, E. An. Quim., Ser. C 1988, 84, 38.
(6) Yuan, J.; Hutchison, A. US Patent 6495688, 2002.
(7) Glushkov, R. G.; Volskova, V. A.; Magidson, O. Y. Khim.-
Farm. Zh. 1967, 1, 25.
(8) Borovik, V. P.; Shkurko, O. P. Russ. Chem. Bull. 2002, 51,
2129.
(9) (a) Dotzauer, B.; Troschütz, R. Synlett 2004, 1039.
(b) Bernier, J.-L.; Hénichart, J.-P. J. Org. Chem. 1981, 46,
4197.
(10) Kumar, U. K. S.; Yadav, A. K.; Venkatesh, C.; Ila, H.;
Junjappa, H. ARKIVOC 2004, (viii), 20.
(11) Zhang, Y. M.; Razler, T.; Jackson, P. F. Tetrahedron Lett.
2002, 43, 8235.
(12) Bundy, G. L.; Banitt, L. S.; Dobrowolski, P. J.; Palmer, J. R.;
Schwartz, T. M.; Zimmermann, D. C.; Lipton, M. F.;
Mauragis, M. A.; Veley, M. F.; Appell, R. B.; Clouse, R. C.;
Daugs, E. D. Org. Process Res. Dev. 2001, 5, 144.
(13) (a) Molina, P.; Arques, A.; Alias, A.; Vinader, M. V.
Tetrahedron Lett. 1991, 34, 4401. (b) Molina, P.; Fresneda,
P. M. J. Chem. Soc., Perkin Trans. 1 1988, 1819.
(14) Lapachev, V. V.; Stadlbauer, W.; Kappe, T. Monatsh. Chem.
1988, 119, 97.
H
75
H
84
H
85
g
h
i
H
84
H
80
H
85
j
H
85
k
l
H
79
H
84
m
n
o
p
q
r
s
H
85
Me
Me
Me
H
77
4-BrC6H4
4-MeC6H4
4-MeC6H4
3-BrC6H4
3-ClC6H4
82
75
(15) Wright, G. E. J. Heterocycl. Chem. 1976, 13, 539.
(16) Eger, K.; Lanzner, W.; Rothenhaüsler, K. Liebigs Ann.
Chem. 1993, 5, 465.
(17) Microwaves in Organic Synthesis, 2nd reprint; Loupy, A.,
Ed.; Wiley-VCH: Weinheim, 2004.
(18) The experiments were performed using a microwave oven
(ETHOS 1600, Milestone) with a power of 600 W specially
designed for organic synthesis.
70
H
73
H
69
a Isolated yields.
(19) Full spectroscopic assignment of compound 5a has been
made in: Borovik, V. P.; Shakirov, M. M.; Shkurko, O. P.;
Vorozhtsov, N. N. Khim. Geterotsikl. Soedin. 2003, 1531.
(20) Preparation of 2,4-Diphenyl-9H-pyrimido[4,5-b]indole
(5a); General Procedure: A mixture of oxindole (0.13 g, 1
mmol), benzonitrile (0.31 g, 3 mmol), and a catalytic amount
of sat. aq NaOH solution was irradiated in a microwave oven
at 180 °C for 4 min (progress of the reaction was followed
by TLC monitoring minute by minute). Then the reaction
mixture was cooled to r.t. and the residue was purified by
column chromatography [using n-hexane–EtOAc (4:1) as
eluent, Merck silica gel 60 mesh]. The solvent was removed
and the product was recrystallized from 95% EtOH.
Selected Data:
The structures of the isolated products 5a–s were corrob-
orated by IR, 1H NMR and 13C NMR spectroscopy, mass
spectrometry, and elemental analysis.19,20
In conclusion, we have developed a novel microwave-as-
sisted synthesis of pyrimido[4,5-b]indoles of potential
synthetic and pharmacological interest. The use of com-
mercial materials, fewer reagents and atomic economy,
good to excellent yields, short reaction times, and solvent-
free conditions are the main advantages of this method.
This method presents a straightforward procedure for the
synthesis of pyrimido[4,5-b]indoles.
Compound 5a: colorless crystals; mp 300–302 °C. IR (KBr):
3225 (NH), 1580, 1547, 1482, 1443, 1398, 1365, 1255,
1209, 760, 744, 693 cm–1. 1H NMR (500.1 MHz, DMSO-d6):
Synlett 2008, No. 2, 177–180 © Thieme Stuttgart · New York

LETTER
d = 7.21 (t, J = 7.7 Hz, 1 H, CH), 7.52 (t, J = 7.5 Hz, 1 H,
Novel and Simple Synthesis of 9H-Pyrimido[4,5-b]indoles
179
692 cm–1. 1H NMR (500.1 MHz, DMSO-d6): d = 7.21 (t, J =
7.5 Hz, 1 H, CH), 7.52 (t, J = 7.7 Hz, 1 H, CH), 7.53–7.57
(m, 2 H, 2 × CH), 7.59 (d, J = 8.0 Hz, 1 H, CH), 7.69–7.73
(m, 2 H, 2 × CH), 7.76 (d, J = 8.0 Hz, 1 H, CH), 7.97 (d, J =
6.7 Hz, 1 H, CH), 8.02 (s, 1 H, CH), 8.46 (d, J = 7.5 Hz, 1 H,
CH), 8.48 (s, 1 H, CH), 12.59 (s, 1 H, NH). 13C NMR (125.8
MHz, DMSO-d6): d = 109.40 (C), 112.06 (CH), 118.40 (C),
120.87, 121.77, 126.29, 127.30, 127.47, 127.80, 128.50,
129.85, 129.89, 130.39, 130.58 (11 × CH), 133.41, 133.50,
139.31, 139.98, 140.34, 156.99, 157.29, 157.78 (8 × C). MS:
m/z (%) = 392 (17) [M+37Cl2], 390 (56) [M+37Cl35Cl], 388
(100) [M+35Cl2], 354 (10), 250 (9), 215 (13), 188 (15), 137
(27), 111 (32), 75 (15). Anal. Calcd for C22H13Cl2N3
(390.27): C, 67.71; H, 3.36; N, 10.77. Found: C, 67.7; H, 3.4;
N, 10.5.
Compound 5j: colorless crystals; mp 300–302 °C. IR (KBr):
3290 (NH), 1577, 1545, 1480, 1429, 1395, 1365, 1249,
1215, 1085, 1008, 844, 799, 740 cm–1. 1H NMR (500.1 MHz,
DMSO-d6): d = 7.23 (t, J = 7.5 Hz, 1 H, CH), 7.53 (dd, J =
7.4, 7.8 Hz, 1 H, CH), 7.59 (d, J = 7.8 Hz, 1 H, CH), 7.61 (d,
J = 8.5 Hz, 2 H, 2 × CH), 7.76 (d, J = 8.3 Hz, 2 H, 2 × CH),
7.82 (d, J = 8.0 Hz, 1 H, CH), 8.06 (d, J = 8.3 Hz, 2 H, 2 ×
CH), 8.55 (d, J = 8.5 Hz, 2 H, 2 × CH), 12.59 (s, 1 H, NH).
13C NMR (125.8 MHz, DMSO-d6): d = 109.04 (C), 111.97
(CH), 118.51 (C), 120.90, 121.91, 127.70, 128.59, 128.81,
129.48, 130.67 (7 × CH), 134.83, 135.08, 136.76, 137.14,
139.19, 157.10, 157.74, 158.26 (8 × C). MS: m/z (%) = 392
(3) [M+37Cl2], 390 (9) [M+37Cl35Cl], 388 (4) [M+35Cl2], 263
(32), 226 (44), 200 (48), 165 (7), 164 (35), 105 (16), 77
(100), 57 (29), 51 (47). Anal. Calcd for C22H13Cl2N3
(390.27): C, 67.71; H, 3.36; N, 10.77. Found: C, 67.6; H, 3.5;
N, 10.7.
Compound 5l: colorless crystals; mp 208–211 °C. IR (KBr):
3100 (NH), 1586, 1536, 1362, 1249, 1210, 1062, 772, 741,
716, 698 cm–1. 1H NMR (500.1 MHz, DMSO-d6): d = 7.21
(t, J = 7.4 Hz, 1 H, CH), 7.48 (dd, J = 7.7, 8.2 Hz, 1 H, CH),
7.52 (dd, J = 7.4, 8.3 Hz, 1 H, CH), 7.59 (d, J = 8.0 Hz, 1 H,
CH), 7.64 (dd, J = 7.8, 8.7 Hz, 1 H, CH), 7.67 (d, J = 8.0 Hz,
1 H, CH), 7.75 (d, J = 7.9 Hz, 1 H, CH), 7.86 (d, J = 7.8 Hz,
1 H, CH), 8.01 (d, J = 7.4 Hz, 1 H, CH), 8.15 (s, 1 H, CH),
8.50 (d, J = 7.6 Hz, 1 H, CH), 8.63 (s, 1 H, CH), 12.58 (1 H,
s, NH). 13C NMR (125.8 MHz, DMSO-d6): d = 109.37 (C),
112.04 (CH), 118.38 (C), 120.83, 121.74, 121.92, 121.93,
126.65, 127.77, 127.82, 130.22, 130.63, 130.80, 131.34
(11 × CH), 132.72, 132.74, 139.30, 140.15, 140.53, 156.94,
157.17, 157.64 (8 × C). MS: m/z (%) = 481 (6) [M+81Br2],
479 (85) [M+81Br79Br], 477 (6) [M+79Br2], 400(16), 319 (17),
216 (20), 181 (32), 155 (28), 114 (30), 102 (100), 75 (88), 52
(38). Anal. Calcd for C22H13Br2N3 (479.17): C, 55.15; H,
2.73; N, 8.77. Found: C, 54.9; H, 2.9; N, 8.6.
Compound 5n: colorless crystals; mp 160–162 °C. IR (KBr):
1579, 1550, 1486, 1439, 1400, 1395, 1250, 1210, 758, 740
cm–1. 1H NMR (500.1 MHz, DMSO-d6): d = 3.05 (s, 3 H,
Me), 7.20 (t, J = 7.7 Hz, 1 H, CH), 7.49–7.57 (m, 4 H, 4 ×
CH), 7.62 (d, J = 7.8 Hz, 1 H, CH), 7.64–7.71 (m, 3 H, 3 ×
CH), 7.92 (d, J = 7.9 Hz, 1 H, CH), 8.00 (d, J = 7.8 Hz, 2 H,
2 × CH), 8.50 (d, J = 7.9 Hz, 2 H, 2 × CH). 13C NMR (125.8
MHz, DMSO-d6): d = 40.25 (Me), 107.05 (C), 110.23 (CH),
117.78 (C), 119.18, 120.03, 127.15, 127.55, 127.95, 128.09,
128.45, 129.33, 130.64 (9 × CH), 138.39, 139.14, 139.97,
156.79, 158.64, 159.20 (6 × C). MS: m/z (%) = 335 (100)
[M+], 258 (14), 230 (23), 129 (18), 105 (43), 103 (39), 77
(55), 57 (40). Anal. Calcd for C23H17N3 (335.41): C, 82.36;
H, 5.11; N, 12.53. Found: C, 82.3; H, 5.2; N, 12.4.
CH), 7.53–7.59 (m, 3 H, 3 × CH), 7.60 (d, J = 8.1 Hz, 1 H,
CH), 7.65–7.72 (m, 3 H, 3 × CH), 7.83 (d, J = 8.0 Hz, 1 H,
CH), 8.04 (dd, J = 1.5, 8.0 Hz, 2 H, 2 × CH), 8.58 (dd, J =
1.5, 8.2 Hz, 2 H, 2 × CH), 12.53 (br, 1 H, NH). 13C NMR
(125.8 MHz, DMSO-d6): d = 108.91 (C), 111.99 (CH),
118.82 (C), 120.56, 121.78, 127.36, 127.79, 128.47, 128.63,
128.78, 129.93, 130.13 (9 × CH), 138.10, 138.58, 139.38,
157.35, 159.02, 159.29 (6 × C). MS: m/z (%) = 321 (27)
[M+], 320 (67) [M+ – 1], 242 (14), 190 (26), 164 (14), 105
(58), 84 (44), 77 (76), 57 (86), 43 (100). Anal. Calcd for
C22H15N3 (321.38): C, 82.22; H, 4.70; N, 13.07. Found: C,
82.1; H, 4.8; N, 12.8.
Compound 5c: colorless crystals; mp 295–296 °C. IR (KBr):
3285 (NH), 1587, 1549, 1433, 1397, 1368, 1252, 1214,
1179, 796, 739, 718 cm–1. 1H NMR (500.1 MHz, DMSO-d6):
d = 2.40, 2.49 (2 × s, 6 H, 2 × Me), 7.20 (t, J = 7.2 Hz, 1 H,
CH), 7.36 (d, J = 7.5 Hz, 2 H, 2 × CH), 7.47–7.51 (m, 3 H,
3 × CH), 7.58 (d, J = 7.8 Hz, 1 H, CH), 7.86 (d, J = 7.7 Hz,
1 H, CH), 7.93 (d, J = 7.4 Hz, 2 H, 2 × CH), 8.46 (d, J = 7.6
Hz, 2 H, 2 × CH), 12.45 (br s, 1 H, NH). 13C NMR (125.8
MHz, DMSO-d6): d = 20.93, 21.01 (2 × Me), 108.51 (C),
111.78 (CH), 118.89 (C), 120.56, 121.76, 127.20, 127.75,
128.73, 129.08, 129.16 (7 × CH), 135.43, 135.76, 138.95,
139.65, 139.81, 157.21, 159.10, 159.42 (8 × C). MS: m/z
(%) = 349 (30) [M+], 348 (100) [M+ – 1], 334 (27), 273 (18),
107 (45), 102 (14), 91 (64), 77 (40), 57 (33). Anal. Calcd for
C24H19N3 (349.44): C, 82.49; H, 5.48; N, 12.03. Found: C,
82.3; H, 5.7; N, 11.7.
Compound 5f: colorless crystals; mp 320 °C (dec.). IR
(KBr): 3260 (NH), 1585, 1543, 1525, 1479, 1440, 1396,
1345, 1255, 1210, 798 cm–1. 1H NMR (500.1 MHz, DMSO-
d6): d = 7.25 (t, J = 7.5 Hz, 1 H, CH), 7.55 (dd, J = 7.5, 7.7
Hz, 1 H, CH), 7.60 (d, J = 7.7 Hz, 1 H, CH), 7.88 (d, J = 7.9
Hz, 1 H, CH), 7.92 (d, J = 8.5 Hz, 2 H, 2 × CH), 7.95 (d, J =
8.6 Hz, 2 H, 2 × CH), 8.65 (d, J = 8.5 Hz, 2 H, 2 × CH), 8.89
(d, J = 8.6 Hz, 2 H, 2 × CH), 12.05 (br, 1 H, NH). 13C NMR
(125.8 MHz, DMSO-d6): d = 110.25 (C), 112.11 (CH),
119.71 (C), 120.09, 122.18, 127.64, 127.75, 128.95, 129.14,
131.66 (7 × CH), 136.44, 138.71, 139.98, 147.51, 148.60,
157.69, 158.50, 159.33 (8 × C). MS: m/z (%) = 411 (19)
[M+], 410 (100) [M+ – 1], 381 (23), 365 (9), 353 (44), 335
(15), 289 (31), 148 (60), 115 (23), 76 (36). Anal. Calcd for
C22H13N5O4 (411.38): C, 64.23; H, 3.19; N, 17.02. Found: C,
64.1; H, 3.3; N, 16.9.
Compound 5g: colorless crystals; mp 276–277 °C. IR (KBr):
3200 (NH), 1575, 1485, 1439, 1402, 1360, 1257, 1220,
1091, 902, 785, 741, 700 cm–1. 1H NMR (500.1 MHz,
DMSO-d6): d = 7.23 (t, J = 7.9 Hz, 1 H, CH), 7.28 (dd,
3JFH = 8.8 Hz, 3JHH = 8.8 Hz, 2 H, 2 × CH), 7.46 (dd, 3JFH
8.8 Hz, 3JHH = 8.7 Hz, 2 H, 2 × CH), 7.55 (dd, J = 7.4, 7.8
=
Hz, 1 H, CH), 7.67 (d, J = 8.1 Hz, 1 H, CH), 7.94 (d, J = 8.0
Hz, 1 H, CH), 8.17 (dd, 4JFH = 5.5 Hz, 3JHH = 8.7 Hz, 2 H, 2
× CH), 8.70 (dd, 4JFH = 5.7 Hz, 3JHH = 8.8 Hz, 2 H, 2 × CH),
11.40 (br s, 1 H, NH). 13C NMR (125.8 MHz, DMSO-d6):
d = 110.16 (C), 112.77 (CH), 115.97 (d, 2JFC = 22.0 Hz, CH),
116.44 (d, 2JFC = 22.0 Hz, CH), 120.43 (C), 121.88, 123.15,
128.45 (3 × CH), 131.27 (d, 3JFC = 8.6 Hz, CH), 132.27 (d,
3JFC = 8.6 Hz, CH), 135.94 (d, 4JFC = 3.2 Hz, C), 136.43 (d,
4JFC = 3.3 Hz, C), 140.25, 158.76, 159.58, 160.18 (4 × C),
164.81 (d, 1JFC = 245.4 Hz, CF), 165.30 (d, 1JFC = 245.4 Hz,
CF). MS: m/z (%) = 357 (77) [M+], 356 (100) [M+ – 1], 260
(6), 233 (8), 208 (13), 178 (9), 149 (5), 114 (4), 95 (8), 69
(13), 57 (10). Anal. Calcd for C22H13F2N3 (357.36): C, 73.94;
H, 3.67; N, 11.76. Found: C, 73.8; H, 3.9; N, 11.6.
Compound 5q: colorless crystals; mp 303–304 °C. IR (KBr):
3250 (NH), 1585, 1550, 1426, 1360, 1250, 1211, 848, 704
cm–1. 1H NMR (300.1 MHz, DMSO-d6): d = 2.37, 2.47 (2 ×
Compound 5i: colorless crystals; mp 233–235 °C. IR (KBr):
3140 (NH), 1587, 1539, 1364, 1249, 1210, 1071, 763, 739,
Synlett 2008, No. 2, 177–180 © Thieme Stuttgart · New York

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M. Adib et al.
LETTER
s, 6 H, 2 × Me), 7.32 (d, J = 8.1 Hz, 2 H, 2 × CH), 7.48 (d,
J = 8.2 Hz, 2 H, 2 × CH), 7.51 (d, J = 8.6 Hz, 1 H, CH), 7.61
(dd, J = 1.8, 8.6 Hz, 1 H, CH), 7.88 (d, J = 8.1 Hz, 2 H, 2 ×
CH), 7.89 (d, J = 1.8 Hz, 1 H, CH), 8.41 (d, J = 8.1 Hz, 2 H,
2 × CH), 12.62 (br s, 1 H, NH). 13C NMR (75.5 MHz,
DMSO-d6): d = 21.06, 21.14 (2 × Me), 107.77, 112.55 (2 ×
C), 113.90 (CH), 120.99 (C), 123.89, 127.94, 128.81,
129.21, 129.34, 129.73 (6 × CH), 135.23, 135.48, 137.83,
140.17, 140.18, 157.48, 159.82, 160.11 (8 × C). MS: m/z
(%) = 429 (65) [M+81Br], 427 (100) [M+79Br], 413 (9), 273
(26), 192 (21), 107 (15), 91 (42), 78 (35). Anal. Calcd for
C24H18BrN3 (428.33): C, 67.30; H, 4.24; N, 9.81. Found: C,
67.2; H, 4.4; N, 9.7.
NMR (300.1 MHz, DMSO-d6): d = 7.42 (t, J = 7.8 Hz, 1 H,
CH), 7.44 (d, J = 8.6 Hz, 1 H, CH), 7.56 (dd, J = 1.8, 8.6 Hz,
1 H, CH), 7.61 (t, J = 7.9 Hz, 1 H, CH), 7.63 (d, J = 7.9 Hz,
1 H, CH), 7.73 (d, J = 1.8 Hz, 1 H, CH), 7.85 (d, J = 7.7 Hz,
1 H, CH), 7.93 (d, J = 7.7 Hz, 1 H, CH), 8.09 (s, 1 H, CH),
8.39 (d, J = 7.9 Hz, 1 H, CH), 8.52 (s, 1 H, CH), 12.67 (br s,
1 H, NH). 13C NMR (75.5 MHz, DMSO-d6): d = 108.50 (C),
112.83, 114.02, 120.26, 121.99, 122.08 (5 × CH), 124.02,
126.74 (2 × C), 127.84 (CH), 130.22, 130.23 (2 × C), 130.70,
130.96, 131.40 (3 × CH), 133.03, 133.10, 138.04, 139.80,
140.10, 157.02, 157.78, 158.18 (8 × C). MS: m/z (%) = 559
(95) [M+81Br279Br], 557 (100) [M+81Br79Br2], 480 (13),
400(56), 192 (9), 181 (14), 155 (17), 79 (21), 57 (20). Anal.
Calcd for C22H12Br3N3 (558.07): C, 47.35; H, 2.17; N, 7.53.
Found: C, 47.3; H, 2.3; N, 7.5%.
Compound 5r: colorless crystals; mp 231–232 °C. IR (KBr):
3150 (NH), 1585, 1543, 1391, 1365, 1250, 760, 690 cm–1. 1H
Synlett 2008, No. 2, 177–180 © Thieme Stuttgart · New York

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