Microwave assisted synthesis of 2,6-substituted aromatic-aminopurine derivatives

Article abstract of DOI:10.1002/jhet.629

A series of novel 2, 6-diaromatic-aminopurines (6a-6t) have been synthesized from guanine and characterized fully. The effects of different catalysts on the N-alkylation of 2-position of purine ring were discussed.

Full text of DOI:10.1002/jhet.629

1140
Microwave Assisted Synthesis of 2, 6-Substituted Aromatic-
Aminopurine Derivatives
Vol 48
Hong-Fei Lu,* Liang-Ze Zhang, Ding-Ming Wu, and Jun-Tao Zhou
Department of Applied Chemistry, School of Material Science and Engineering,
Jiangsu University of Science and Technology, Zhenjiang China
*E-mail: zjluhf1979@hotmail.com
Received May 13, 2010 Revised 8 July 2010; accepted 8 August 2010
DOI 10.1002/jhet.629
Published online 8 June 2011 in Wiley Online Library (wileyonlinelibrary.com).
A series of novel 2, 6-diaromatic-aminopurines (6a–6t) have been synthesized from guanine and char-
acterized fully. The effects of different catalysts on the N-alkylation of 2-position of purine ring were
discussed.
J. Heterocyclic Chem., 48, 1140 (2011).
INTRODUCTION
reaction [6]. Because the reaction activity of 6-position
is higher than that of 2-position in the same purine
ring, different aliphatic amines can be introduced into
the purine ring selectively by controlling the reaction
temperature [7]. However, aromatic amines are very
difficult to be introduced due to their low activity of
nucleophilic substitution, and reported scarcely. Mean-
while, to increase the reaction activity of 2-position,
N,N-dimethylformamide (DMF) is often used as solvent
[5,6].
Purine derivatives are often shown to possess a wide
range of interesting pharmacological activities [1]. For
example, the purine nucleus is the key structural feature
of many types of biologically active compounds, such
as CDK inhibitors [2], and Hsp 90 family inhibitors [3].
The results indicate that purine derivatives should com-
bine with RNA of the virus cell when 2-position and 6-
position in the purine ring are introduced with the
ylamine in the form of CAN bond. They can inhibit the
reproduction of the virus cell in the body, thus have the
fine medicine activity [4]. For instance, abacavir
(Scheme 1) is being clinical to cure for AIDS [5]. Con-
sequently, purines have become a well-sought privileged
class of compounds in drug discovery programs and a
practical strategy for the construction of a library of
purines that should aid both SAR studies and screenings
for new leads.
From the purine structure, we can find that the main
reason causes the activity of 2-position to decline is the
existence of 6-ylamine which shares electrons with pu-
rine ring by pAp bond. But acids can occupy the elec-
trons of N atom and destroy pAp bond, and will
increase reaction activity of 2-position, so we used acids
as catalysts in the reactions in present study. Further-
more, the reaction was carried out under microwave
conditions, the corresponding reaction time is thus short-
ened and the yield is also improved greatly.
In the literatures, most methods about the preparation
of 2,6-diaminepuine derivatives involved a N-alkylation
C
V
2011 HeteroCorporation

September 2011
Microwave Assisted Synthesis of 2, 6-Substituted Aromatic-Aminopurine
Derivatives
1141
Scheme 1
obtained by the reaction of compounds 5a–5d with cor-
responding arylamine in the presence of TFA(?) in buta-
nol (BuOH). And compounds 5a–5d were prepared by
reaction between compound 4 and the corresponding ar-
ylamine in the presence of Et3N in BuOH.
N-alkylation reaction plays an important role in the
preparation of 2,6-diaminepurine from 2,6-dichlo-
ropuine. We concluded that protonation of 2,6-diamine-
purine activate the chloro atom toward nucleophilic sub-
stitution reaction, so we carried out our experiment to
synthesis 6a–6d under acid conditions. However, 2,6-
diaminepurine was failed to obtained from 2,6-dichloro-
purine, which was ascribe to the protonation reduction
of amino groups of aromatic amines. Triethylamine
could activate the aromatic amines toward nucleophilic
substitution reactions, but the reaction needed 72 h and
the color of the product was badly. The reaction was
carried out quickly under microwave conditions and
only 18 minutes was needed to obtain the desired prod-
ucts in about 80% yields. Many byproducts were formed
when the compounds 6e–6t were prepared under the
base conditions, however, the desired products were
RESULTS AND DISCUSSION
The synthetic pathways are shown in Scheme 2. Com-
pounds 1–3 were synthesized according to the literature
method [8], and compound 4 according to the literature
method [9]. The title compounds 6a–6d were obtained
by the reaction of compound 3 with corresponding aryl-
amine in DMF, and the title compounds 6e–6t were
Scheme 2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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H.-F. Lu, L.-Z. Zhang, D.-M. Wu, and J.-T. Zhou
Vol 48
Table 1
Yield of products on different catalyst.
Compd.
HCl (%)
TFA (%)
AlCl3 (%)
Compd.
HCl (%)
TFA (%)
AlCl3 (%)
6e
6f
6g
6h
6i
6j
6k
6l
35.9
29.4
36.8
41.4
33.9
21.0
37.7
30.6
55.2
49.9
49.1
62.3
49.8
50.6
54.2
44.7
54.7
49.1
50.7
67.4
56.8
45.9
51.7
46.1
6m
6n
6o
6p
6q
6r
6s
31.2
23.4
19.8
22.7
27.9
45.0
44.6
43.1
69.2
51.1
48.8
54.1
57.2
61.2
50.9
69.7
68.7
53.9
45.1
45.8
65.2
66.9
68.1
71.3
6t
Data of all the compounds
obtained with satisfied yields under the acid conditions.
Different acids were used to prompt the reactions for
the desired products with good to best yields, and the
results are summarized in Table 1. It is obvious that
TFA and aluminum chloride anhydrous are better than
HCl as catalyst (Table 1).
N2,9-Diacetylguanine (2). White crystal; yield, 95.8%; m.p.:
>250ꢀC1H NMR (DMSO, 400 MHz) d: 2.16 (s, 3H,
C2ACOCH3), 2.50 (s, 3H, N9ACOCH3), 8.10 (br, 2H, ANHþ
ACH), 11.56 (s, 1H, AOH); MS (EI) m/z: 234.10 (M-1); Anal.
calcd for C9H9N5O3: C 45.96, H 3.86, N 29.78; found C 45.87,
H 3.90, N 29.68.
In conclusion, a series of novel 2-substituted purine
derivatives were synthesized under microwave condi-
tions using acids as the catalysts, which provide a new
way to access a large number of 2,6-diaminepurine
derivatives.
2-Amino-6-chloropurine (3). Pale yellow solid: yield,
1
75.8%: m.p.: >250ꢀC H NMR (DMSO, 400MHz) d: 6.75 (s,
3H, ANH2þANH), 8.01 (s, 1H, ACH); MS (EI) m/z: 169.13
(M-1); Anal. calcd for C5H4N5Cl: C 35.42, H 2.38, N 41.30;
found C 35.53, H 2.41, N 41.25.
2,6-Dichloropuine (4). white solid; yield, 16.4%; m.p.: 182–
183ꢀC (literature value: 180–182ꢀC); 1H NMR (DMSO, 400
MHz) d: 8.43 (s, 1H, ACH), 11.99 (s, 1H, ANH); MS (EI) m/
z: 187.11 (M-1); Anal. calcd for C5H2 N4Cl2: C 31.77, H 1.07,
N 29.64; found C 31.69, H 1.11, N 29.62.
EXPERIMENTAL
2-Chloro-6-anilinepurine (5a). white solid; yield, 86.7 %,
m.p.: > 250ꢀC; IR (KBr) m: 3439, 2781, 1635, 1560, 1496,
The melting points were determined on Yansco melting
point apparatus and were uncorrected; 1H NMR data were
recorded on a Bruker-Avance DXP 400 MHz NMR spectrome-
ter using Tertramethylsilane(TMS) as a internal standard and
DMSO-d6 as solvent; PE-2400 atom analytic apparatus; 6110
MS from Agilen company. MAS-II microwave assisted synthe-
sis extract apparatus.
1434, 1303, 938, 729 cmꢁ1 1H NMR (DMSO, 400 MHz) d:
;
7.06 –7.86 (m, 5H, AArAH), 8.30 (s, 1H, ACH), 10.21 (s,
1H, C6ANH), 13.39 (s, 1H, N9AH); MS (EI) m/z: 246.2
(Mþ1); Anal. calcd for C11H8N5Cl: C 53.78, H 3.28, N 28.51;
found C 53.66, H 3.34, N 28.41.
2-Chloro-6-o-chloroanilinepurine (5b). white solid; yield,
61.3 %, m.p.: >250ꢀC; IR (KBr) m: 3377, 3109, 2961, 1627,
2-Chloro-6-arylaminopurine derivatives (5a–5d). To
a
1577, 1474, 1348, 1320, 1246, 962, 930, 787, 741 cmꢁ1 1H
;
three-necked flask, 2,6-dichloropurine (10 mmol, 1.9 g), BuOH
(45 mL) and corresponding arylamine (50 mmol) were added,
under nitrogen with 300W microwave at 70ꢀC until the reac-
tion was over. The solid was collected by filtration and recrys-
tallized with MeOH to give desired product.
NMR (DMSO, 400 MHz) d: 7.28 –7.67 (m, 4H, AArAH), 8.26
(s, 1H, ACH), 9.77 (s, 1H, C6ANH), 13.01 (s, 1H, N9AH); MS
(EI) m/z: 280.0 (Mþ1) ; Anal. calcd for C11H7N5Cl2: C 47.17, H
2.52, N 25.00; found C 47.29, H 2.43, N 24.89.
2-Chloro-6-p-chloroanilinepurine (5c). white solid; yield,
74.5 %, m.p.: >250ꢀC; IR (KBr) m: 3264, 3133, 3051, 2763, 2683,
1630, 1588, 1562, 1492, 1444, 1397, 1351, 1254, 936, 847, 805
cmꢁ1 1H NMR (DMSO, 400 MHz) d: 7.30 –7.69 (m, 4H,
;
2-Amino-6-arylamino-purine derivatives (6a–6d). To
a
three-necked flask, 2-amino-6-chloropurine (10 mmol, 1.7 g),
DMF (30 mL), corresponding amine (30 mL), triethylamine (5
mL) were added , under nitrogen, and then the reaction was
carried out with 300W microwave at 90ꢀC for 18 min. The
mixture was cooled to the room temperature, filtered and
recrystallized with methanol to yield the desired product.
2,6-Diarylaminopurine derivatives (6e–6t). To a three-
necked flask, 2-chloro-6-arylaminopurine (10 mmol), normal
butyl alcohol (30 mL), corresponding amine (25 mL) and
acid (10 mmol) were added, under nitrogen, and then the
reaction was carried out with 300W microwave at 110ꢀC for
5 min. The mixture was cooled to the room temperature, fil-
tered and recrystallized with DMF to yield the desired
product.
AArAH), 8.51 (s, 1H, ACH), 9.52 (s, 1H, C6ANH), 12.00 (s, 1H,
N9AH); MS (EI) m/z: 280.0 (Mþ1) ; Anal. calcd for C11H7N5Cl2:
C 47.17, H 2.52, N 25.00; found C 47.28, H 2.47, N 24.87.
2-Chloro-6-o-methoxyanilinepurine (5d). white solid; yield,
78.2 %, m.p.: > 250ꢀC; IR (KBr) m: 3275, 3140, 3067, 3002,
2955, 2779, 2637, 2069, 1637, 1593, 1565, 1445, 1250, 1175,
1102, 934, 807, 721 cmꢁ1 1H NMR (DMSO, 400 MHz) d:
;
3.76 (s, 3H, AOCH3), 6.94–7.70 (m, 4H, AArAH), 8.26 (s,
1H, ACH), 10.04 (s, 1H, C6ANH), 11.99 (s, 1H, N9AH); MS
(EI) m/z: 276.0 (Mþ1); Anal. calcd for C12H10N5OCl: C
52.28, H 3.66, N 25.40; found C 52.36, H 3.58, N 25.34.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

September 2011
Microwave Assisted Synthesis of 2, 6-Substituted Aromatic-Aminopurine
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1143
2-Amino-6-anlilinepurine (6a). white solid; m.p.: > 250ꢀC;
1H NMR (DMSO, 400 MHz) d: 7.16 –7.98 (m, 5H, AArAH),
7.64 (s, 2H, ANH2), 8.33 (s, 1H, ACH), 11.24 (s, 1H,
C6ANH), 13.64 (s, 1H, N9AH); MS (EI) m/z: 227.1 (Mþ1);
Anal. calcd for C11H10N6: C 58.40, H 4.46, N 37.15; found C
58.29, H 4.55, N 37.03.
2-Amino-6-m-chloroanilinepurine (6b). white solid; m.p.:
258–260ꢀC; 1H NMR (DMSO, 400 MHz) d: 6.75 –7.51 (m,
4H, ArAH), 7.32 (s, 2H, ANH2), 8.30 (s, 1H, ACH), 11.17 (s,
1H, C6ANH), 12.98 (s, 1H, N9AH); MS (EI) m/z: 261.3
(Mþ1); Anal. calcd for C11H9N6Cl: C 50.68, H 3.48, N 32.24;
found C 50.56, H 3.55, N 32.19.
2,6-Di-m-chloroanilinepurine (6j). white solid; m.p.:
>270ꢀC; IR (KBr) m: 3209, 3131, 2950, 1636, 1587, 1550,
1424, 1292, 1188, 1067, 743 cmꢁ1 1H NMR (DMSO, 400
;
MHz) d: 6.89–7.87 (m, 8H, AArAH), 8.45 (s, 1H, ACH), 9.65
(s, 1H, C6ANH), 10.18 (s, 1H, C2ANH), 13.76 (s, 1H,
N9AH); MS (EI) m/z: 371.0 (Mþ1); Anal. calcd for
C17H12N6Cl2: C 55.00, H 3.26, N 22.64; found C 55.09, H
3.21, N 22.69.
2-p-Chloroaniline-6-m-chloroanilinepurine
solid; m.p.: >270ꢀC; IR (KBr) m: 3184, 3122, 2986, 2839,
1636, 1580, 1418, 1299, 1055, 817, 744 cmꢁ1 1H NMR
(6k). white
;
(DMSO, 400 MHz) d: 6.86–7.85 (m, 8H, AArAH), 8.44 (s,
1H, ACH), 9.58 (s, 1H, C6ANH), 10.13 (s, 1H, C2ANH),
13.68 (s, 1H, N9AH); MS (EI) m/z: 371.0 (Mþ1); Anal. calcd
for C17H12N6Cl2: C 55.00, H 3.26, N 22.64; found C 55.08, H
3.21, N 22.68.
2-Amino-6-p-chloroanilinepurine (6c). white solid; m.p.:
1
>250ꢀC; H NMR (DMSO, 400 MHz) d: 7.12 –7.80 (m, 4H,
ArAH), 7.55 (s, 2H, ANH2), 8.27 (s, 1H, ACH), 11.05 (s, 1H,
C6ANH), 13.20 (s, 1H, N9AH); MS (EI) m/z: 261.3 (Mþ1);
Anal. calcd for C11H9N6Cl: C 50.68, H 3.48, N 32.24; found
C 50.57, H 3.44, N 32.35.
2-p-Methoxyaniline-6-m-chloroanilinepurine (6l). white
solid; m.p.: 262–264ꢀC; IR (KBr) m: 3204, 3105, 2958, 1636,
1560, 1508, 1420, 1244, 1184, 1032, 765 cmꢁ1 1H NMR
;
2-Amino-6-p-methoxyanilinepurine (6d). white solid; m.p.:
1
>250ꢀC; H NMR (DMSO, 400 MHz) d: 3.76 (s, 3H, AOCH3),
(DMSO, 400 MHz) d: 3.77 (s, 3H, AOCH3), 6.77–7.68 (m,
8H, AArAH), 8.48 (s, 1H, ACH), 9.60 (s, 1H, C6ANH),
10.06 (s, 1H, C2ANH), 13.32 (s, 1H, N9AH); MS (EI) m/z:
367.1 (Mþ1); Anal. calcd for C18H15ClN6O: C 58.94, H 4.12,
N 22.91; found C 59.00, H 4.15, N 22.86.
6.97–7.84 (m, 4H, ArAH), 7.54 (s, 2H, ANH2), 8.27 (s, 1H,
ACH), 11.04 (s, 1H, C6ANH), 13.28 (s, 1H, N9AH); MS (EI)
m/z: 257.6 (Mþ1); Anal. calcd for C12H12N6O: C 56.24, H
4.72, N 32.79; found C 56.33, H 4.67, N 32.88.
2,6-Dianlilinepurine (6e). white solid; m.p.: > 270ꢀC; IR
(KBr) m: 3442, 3292, 3221, 3118, 2975, 2853, 1654, 1585,
2-Aniline-6-p-chloroanilinepurine (6m). white solid; m.p.:
>270ꢀC; IR (KBr) m: 3281, 3212, 3116, 2856, 2304, 1657,
1
1616, 1492, 1424, 1311, 1238, 1087, 829, 761 cmꢁ1; H NMR
1
1411, 1320, 1045, 750 cmꢁ1; H NMR (DMSO, 400 MHz) d:
(DMSO, 400 MHz) d: 6.76–7.57 (m, 9H, AArAH), 8.55 (s,
1H, ACH), 9.54 (s, 1H, C6ANH), 10.02 (s, 1H, C2ANH),
12.94 (s, 1H, N9AH); MS (EI) m/z: 337.0 (Mþ1); Anal. calcd
for C17H13N6Cl: C 60.63, H 3.89, N 24.95; found C 60.69, H
3.82, N 24.88.
6.96 –7.99 (m, 10H, AArAH), 8.53 (s, 1H, ACH), 9.38 (s,
1H, C6ANH), 10.21 (s, 1H, C2ANH), 12.56 (s, 1H, N9AH);
MS (EI) m/z: 303.1 (Mþ1); Anal. calcd for C17H14N6: C
67.54, H 4.67, N 27.80; found C 67.66, H 4.58, N 27.89.
2-m-Chloroaniline-6-anlilinepurine (6f). white solid; m.p.:
248–250ꢀC; IR (KBr) m: 3430, 3228, 3128, 3051, 1634, 1579,
1498, 1434, 1318, 1254, 1177, 745 cmꢁ1; 1H NMR (DMSO, 400
MHz) d: 6.70–7.73 (m, 9H, AArAH), 8.54 (s, 1H, ACH), 9.50 (s,
1H, C6ANH), 9.74 (s, 1H, C2ANH), 13.12 (s, 1H, N9AH); MS
(EI) m/z: 337.1 (Mþ1); Anal. calcd for C17H13N6Cl: C 60.63, H
3.89, N 24.95; found C 60.56, H 3.91, N 24.87.
2-p-Chloroaniline-6-anlilinepurine (6g). white solid; m.p.:
>270ꢀC; IR (KBr) m: 3425, 3263, 3194, 1662, 1637, 1557,
1491, 1465, 1234, 1105, 948, 748; 1H NMR (DMSO, 400 MHz)
d: 6.84–7.75 (m, 9H, AArAH), 8.55 (s, 1H, ACH), 9.55 (s, 1H,
C6ANH), 9,76 (s, 1H, C2ANH), 12.98 (s, 1H, N9AH); MS (EI)
m/z: 337.1 (Mþ1); Anal. calcd for C17H13N6Cl: C 60.63, H
3.89, N 24.95; found C 60.56, H 3.94, N 24.86.
2-m-Chloroaniline-6-p-chloroanilinepurine
(6n). white
solid; m.p. >270ꢀC; IR (KBr) m: 3317, 3225, 2975, 2646,
2314, 1662, 1614, 1495, 1416, 1296, 1093, 1035, 825, 737
cmꢁ1 1H NMR (DMSO, 400 MHz) d: 7.16–7.94 (m, 8H,
;
AArAH), 8.56 (s, 1H, ACH), 9.49 (s, 1H, C6ANH), 9.64 (s,
1H, C2ANH), 12.89 (s, 1H, N9AH); MS (EI) m/z: 371.0
(Mþ1); Anal. calcd for C17H12N6Cl2: C 55.00, H 3.26, N
22.64; found C 54.92, H 3.32, N 22.68.
2,6-Di-p-chloroanilinepurine (6o). white solid; m.p.:
>270ꢀC; IR (KBr) m: 3115, 2966, 2864, 2783, 1631, 1579,
1492, 1347, 1251, 934, 825 cmꢁ1 1H NMR (DMSO, 400
;
MHz) d: 7.38–7.98 (m, 8H, AArAH), 8.33 (s, 1H, ACH),
10.36 (s, 1H, C6ANH), 10.84 (s, 1H, C2ANH), 11.52 (s, 1H,
N9AH); MS (EI) m/z: 371.0 (Mþ1); Anal. calcd for
C17H12N6Cl2: C 55.00, H 3.26, N 22.64; found C 55.07, H
3.23, N 22.60.
2-p-Methoxyaniline-6-anlilinepurine (6h). white solid; m.p.:
>270ꢀC; IR (KBr) m: 3442, 3122, 3057, 1648, 1625, 1594,
1557, 1497, 1362, 1237, 1045, 835 cmꢁ1 1H NMR (DMSO,
;
2-p-Methoxyaniline-6-p-chloroanilinepurine
solid; m.p.: >270ꢀC; IR (KBr) m: 3125, 2959, 1898, 1652,
1557, 1390, 1234, 1198, 1044, 834, 789 cmꢁ1 1H NMR
(6p). white
400 MHz) d: 3.70 (s, 3H, AOCH3), 6.60–7.72 (m, 9H,
AArAH), 8.48 (s, 1H, ACH), 9.22 (s, 1H, C6ANH), 9.67 (s,
1H, C2ANH), 13.07 (s, 1H, N9AH); MS (EI) m/z: 333.1
(Mþ1); Anal. calcd for C18H16N6O: C 65.05, H 4.85, N 25.29;
found C 65.13, H 4.89, N 25.35.
;
(DMSO, 400 MHz) d: 3.76 (s, 3H, AOCH3), 7.40–7.97 (m,
8H, AArAH), 8.32 (s, 1H, ACH), 10.34 (s, 1H, C6ANH),
10.85 (s, 1H, C2ANH), 11.60 (s, 1H, N9AH); MS (EI) m/z:
367.1 (Mþ1); Anal. calcd for C18H15ClN6O: C 58.94, H 4.12,
N 22.91; found C 58.99, H 4.08, N 22.87.
2-Anliline-6-m-chloroanilinepurine (6i). white solid; m.p.
>270ꢀC; IR (KBr) m: 3210, 3123, 2834, 2590, 2306, 1636,
1579, 1442, 1306, 1235, 750 cmꢁ1 1H NMR (DMSO, 400
;
2-Aniline-6-p-methoxyanilinepurine (6q). white solid;
m.p.: >270ꢀC; IR (KBr) m: 3443, 3122, 3056, 1646, 1626,
MHz) d: 6.87–7.65 (m, 9H, AArAH), 9.56 (s, 1H, C6ANH),
10.23 (s, 1H, C6ANH), 13.44 (s, 1H, N9AH); MS (EI) m/z:
337.1 (Mþ1); Anal. calcd for C17H13N6Cl: C 60.63, H 3.89, N
24.95; found C 60.71, H 3.82, N 25.00.
1594, 1558, 1497, 1237, 1045, 835 cmꢁ1 1H NMR (DMSO,
;
400 MHz) d: 3.66 (s, 3H, AOCH3), 6.67–7.73 (m, 9H,
AArAH), 8.31 (s, 1H, ACH), 9.26 (s, 1H, C6ANH), 9.74 (s,
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Vol 48
REFERENCES AND NOTES
1H, C2ANH), 13.12 (s, 1H, N9AH); MS (EI) m/z: 332.0
(Mþ1); Anal. calcd for C18H16N6O: C 65.05, H 4.85, N 25.29;
found C 65.00, H 4.89, N 25.26.
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G.; Zimmermann, J. Bioorg Med Chem Lett 1999, 9, 91; (e) Legraver-
end, M.; Ludwig, O.; Bisagni, E. Bioorg Med Chem 1999, 7, 1281.
[3] (a) Giner-Sorolla, A.; Segarra, J. T.; Brooks, M. H. J Med
Chem 1978, 21, 344; (b) Chiosis, G.; Lucas, B.; Rosen, N. Bioorg
Med Chem 2002, 10, 3555; (c) Lucas, B.; Rosen, N.; Chiosis, G. J.
Comb Chem 2001, 3, 518.
2-m-Methoxyaniline-6-p-methoxyanilinepurine (6r). white
solid; m.p.: >270ꢀC; IR (KBr) m: 3224, 3057, 2953, 1655,
1511, 1300, 1177, 1036, 934, 823, 732 cmꢁ1 1H NMR
;
(DMSO, 400 MHz) d: 3.76 (s, 3H, AOCH3), 6.78–7.79 (m,
8H, AArAH), 8.85 (s, 1H, ACH), 9.48 (s, 1H, C6ANH),
10.73 (s, 1H, C2ANH), 12.25 (s, 1H, N9AH); MS (EI) m/z:
367.1 (Mþ1); Anal. calcd for C18H15N6OCl: C 58.94, H 4.12,
N 22.91; found C 58.89, H 4.06, N 22.85.
2-p-Chloroaniline-6-p-methoxyanilinepurine (6s). white
solid; m.p.: >270ꢀC; IR (KBr) m: 3114, 2965, 2834, 1909,
1652, 1509, 1360, 1046, 831, 786 cmꢁ1 1H NMR (DMSO,
;
400 MHz) d:3.77 (s, 3H, AOCH3), 6.96–7.79 (m, 8H,
AArAH), 8.93 (s, 1H, ACH), 9.70 (s, 1H, C6ANH), 10.63 (s,
1H, C2ANH), 11.65 (s, 1H, N9AH); MS (EI) m/z: 367.1
(Mþ1); Anal. calcd for C18H15N6OCl: C 58.94, H 4.12, N
22.91; found C 58.88, H 4.07, N 22.86.
[4] (a) Melissa, P.; Jiang, J.; Athena, M. K. J Med Chem 2005,
48, 4910; (b) Parthasarathi, D.; Kiran, K.; Naresh, K. Tetrahedron Lett
2008, 49, 992; (c) Iain, W.; Caroline, A.; Rupert, A. Bioorg Med
Chem Lett 2008, 18, 798.
[5] Graul, A.; Leeson, P. A. Drugs Future 1998, 23, 1155–1167.
[6] (a) Minghong, Z.; Ireneusz, N.; John, F. C.; Morris, J. R. J
Org Chem 2006, 71, 4216; (b) Michel, L.; David, S. G. Bioorg Med
Chem 2006, 14, 3987; (c) Lucie, V.; Sandrine, P.; Olivier, L.; Laurent,
M. Bioorg Med Chem Lett 2006, 16, 3144; (d) Lech, C.; Liladhar, W.;
Mahavir, P. A. Org Pro Res Dev 2006, 10, 799.
2,6-Di-p-methoxyanilinepurine (6t). white solid; m.p.:
>270ꢀC; IR (KBr) m: 3123, 2958, 2833, 1888, 1652, 1510,
1360, 1301, 1103, 952, 829 cmꢁ1 1H NMR (DMSO, 400
;
MHz) d: 3.76 (s, 6H, AOCH3), 6.92 –7.76 (m, 8H, AArAH),
8.72 (s, 1H, ACH), 9.55 (s, 1H, C6ANH), 10.85 (s, 1H,
C2ANH), 11.78 (s, 1H, N9AH); MS (EI) m/z: 363.9 (Mþ1);
Anal. calcd for C19H18N6O2: C 62.97, H 5.01, N 23.19; found
C 63.03, H 4.99, N 23.15.
[7] Amy, G. T.; Andrew, P. C. J Comb Chem 2004, 6, 171.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet