Sequential three-component synthesis of 1,4-bis[6,9-dihydro-6-oxo-9- Phenyl-1H-purin-2-yl]piperazines

Article abstract of DOI:10.3184/174751912X13505755737168

A simple one-pot efficient method for the synthesis of 1,4-bis[6,9-dihydro- 6-oxo-9-phenyl-1H-purin-2-yl]piperazines by a domino three-component process involves an aza-Wittig reaction/heterocyclisation in the presence of sodium ethoxide as catalyst. Ethyl 1-phenyl-5-[(triphenylphosphoranylidene)amino]-1H- imidazole-4-carboxylate reacted with aromatic isocyanate to give carbodiimide intermediates, followed by addition of piperazines to give the corresponding guanidine intermediates. The guanidine intermediates were cyclised in the presence of a catalytic amount of sodium ethoxide to give 1,4-bis(6,9-dihydro-6- oxo-9-phenyl-1H-purin-2-yl)piperazine derivatives in good yields.

Full text of DOI:10.3184/174751912X13505755737168

JOURNAL OF CHEMICAL RESEARCH 2012
RESEARCH PAPER 703
DECEMBER, 703–705
Sequential three-component synthesis of 1,4-bis[6,9-dihydro-6-oxo-9-
phenyl-1H-purin-2-yl]piperazines
Zheng Dong Fang*, Di Fang and Quan Cheng
College of Chemistry and Environmental Engineering, Hubei Normal University, Huangshi 435002, P. R. China
A simple one-pot efficient method for the synthesis of 1,4-bis[6,9-dihydro-6-oxo-9-phenyl-1H-purin-2-yl]piperazines
by a domino three-component process involves an aza-Wittig reaction/heterocyclisation in the presence of sodium
ethoxide as catalyst. Ethyl 1-phenyl-5-[(triphenylphosphoranylidene)amino]-1H-imidazole-4-carboxylate reacted with
aromatic isocyanate to give carbodiimide intermediates, followed by addition of piperazines to give the correspond-
ing guanidine intermediates. The guanidine intermediates were cyclised in the presence of a catalytic amount of
sodium ethoxide to give 1,4-bis(6,9-dihydro-6-oxo-9-phenyl-1H-purin-2-yl)piperazine derivatives in good yields.
Keywords: multi-point reaction, purine, 1,4-bis[6,9-dihydro-6-oxo-9-phenyl-1H-purin-2-yl]piperazines, bioactive heterocycles
Substituted purines are widely used as potent inhibitors, antag-
onists, and receptors in living organisms1–3. The biological
activities displayed by purines are conferred by a judicious
choice of the nature of the substituents that can be combined
on the N-1, C-2, N-3, C-6, N-7, C-8 and N-9 centres of the
purine moiety4,5. Purines bearing C-substituents at position 2
are available by cyclisation reactions of 4-aminoimidazole-5-
carboxamides or nitriles with derivatives of carboxylic acids
(esters, orthoesters etc.)6–8, while purines bearing C-substitu-
ents at position 8 are prepared by similar cyclisations from
5,6-diaminopyrimidines9–10. Other possible approaches to the
C–C-purines are radical or nucleophilic substitutions or via
generation of carbanions or organometallics (Li, Mg or Zn) on
The iminophosphorane 1 reacted with aromatic isocyanates
to give triphenylphosphine oxide and carbodiimides 2. The
reaction proceeded smoothly in THF at room temperature. The
reaction of carbodiimides 2 with piperazine derivatives at room
temperature gave intermediate guanidines 3 via initial double
nucleophilic addition of piperazine to the carbodiimide.
Even in refluxing toluene, 3 did not cyclise. However, in dry
ethylene chloride and in the presence of a catalytic amount
of EtONa, compounds 3 were converted smoothly to the 1,4-
bis[6-oxo-9-phenyl-purin-2-yl]piperazines 4 in satisfactory
yields at room temperature. We found that heterocyclisation
occurred via nucleophilic displacement of the neighbouring
ester ethoxide group to provide the target compounds 4 for
intermolecular hetero conjugate addition annulations. No
matter whether alkyl substituted piperazine or aryl substituted
piperazines were used, the cyclisation proceeded very smoothly
with the same regioselectivity. In position 2, whether the sub-
stituents on the benzene are electron-withdrawing or electron-
donating groups, the cyclisation can be completed easily under
mild conditions.
The structure of compounds 4 was confirmed by their
analytical and spectral data (IR, 1H NMR and MS). For
example, the IR spectrum of 4a showed a strong absorption
at 1698 cm−1 assigned to the C=O group. In the 1H NMR spec-
trum, the piperazine ring (–CH2) proton appears at 2.67 ppm.
The signals attributing to the imidazole proton and other aryl
proton were found at 7.89 ppm and 7.22–7.65 ppm as a singlet
and multiplet. The electrospray ionisation mass spectrum
(ESI-MS) for 4a showed the expected molecular ion peaks
which showed m/z at 659.24 (M+H)+ and the two-dimensional
ionisation pattern is in accord with the proposed structure.
the purine skeleton followed by reaction with electrophiles11–13
.
However, the above mentioned synthesis methods were char-
acterised by long reaction times and low yields. Recently, we
have become interested in the synthesis of fused pyrimidinones
via aza-Wittig reactions. As a continuation of our research
for new bioactive heterocycles14, we report here a sequential
three-component synthesis of 1,4-bis[6-oxo-9-phenyl-1H-
purin-2-yl]piperazines via multi-point reactions.
Results and discussion
The key iminophosphorane 1 was synthesised according to the
literature15, m.p.124–125 °C; IR (KBr): 1689 (C=O), 1542,
1502, 1438, 1417, 1137 cm−1. Reaction of iminophosphorane
1 with aromatic isocyanates, followed by heterocyclisation
with addition of nucleophilic piperazines in the presence of a
base, resulting directly in the formation of the corresponding
1,4-bis[6-oxo-9-phenyl-1H-purin-2-yl]piperazines (Scheme 1).
The results are listed in Table 1.
Scheme 1
* Correspondent. E-mail: zdfang2007@163.com

704 JOURNAL OF CHEMICAL RESEARCH 2012
Table
1
Preparation of 1,4-bis[6-oxo-9-phenyl-1H-purin-2-
45.6 (CH2), 46.6 (CH), 119.0 (N–C), 121.4, 122.4, 122.6, 124.8,
128.3, 129.0, 129.7, 132.4, 137.4 (ArC), 137.8 (N–C), 148.9 (N=C),
151.2 (N=C), 160.2 (C=O); ESI-MS m/z: 673.19 (M+H)+. Anal. Calcd
for C39H32N10O2: C, 69.63; H, 4.79; N, 20.82. Found: C, 69.76; H,
4.88; N, 20.69%.
1,4-Bis[6,9-dihydro-6-oxo-1,9-diphenyl-1H-purin-2-yl]-2,5-
dimethylpiperazine (4c): White crystals; m.p. 288–289 °C; IR (KBr):
3305, 1687 (C=O), 1572, 1358, 1112 cm−1; 1H NMR (CDCl3,
300 MHz): δ 1.10 (d, J = 6.8 Hz, 6H, 2CH3), 2.52 (d, J = 7.2 Hz, 4H,
2CH2), 3.03 (m, 2H, 2CH), 7.01 (s, 2H, ArH), 7.23–7.65 (m, 18H,
ArH), 7.95 (s, 2H, imidazole-H); 13C NMR(CDCl3, 75 MHz): δ 16.3
(CH3), 41.6 (CH2), 46.9 (CH), 119.0 (N–C), 121.4, 122.4, 122.6,
124.8, 128.3, 129.0, 129.7, 132.4, 137.4 (ArC), 137.8 (N–C), 148.9
(N=C), 151.2 (N=C), 160.2 (C=O); ESI-MS m/z: 687.30 (M+H)+.
Anal. Calcd for C40H34N10O2: C, 69.96; H, 4.99; N, 20.40. Found: C,
69.82; H, 4.87; N, 20.34%.
yl]piperazines
Compd
Ar
R
Yield/%a
4a
4b
4c
4d
Ph
Ph
Ph
Ph
H
2-Me
2,5-diMe
Ph
83
80
72
71
4e
Ph
74
4f
4g
4h
4-MeC6H4
4-MeC6H4
4-MeC6H4
H
78
73
68
2-Me
2,5-diMe
4i
4-MeC6H4
71
1,4-Bis[6,9-dihydro-6-oxo-1,9-diphenyl-1H-purin-2-yl]-2-phenyl-
piperazine (4d): White crystals; m.p. > 300 °C; IR (KBr): 3342, 2943,
4j
4-MeC6H4
70
1
1688 (C=O), 1455, 1321 cm−1; H NMR (CDCl3, 300 MHz): δ 2.69
(t, J = 7.2 Hz, 4H, 2CH2), 2.87 (d, J = 7.2 Hz, 2H, CH2), 4.12 (t,
J = 6.8 Hz, 1H, CH), 7.00 (s, 2H, ArH), 7.16–7.48 (m, 23H, ArH),
7.96 (s, 2H, imidazole-H); 13C NMR(CDCl3, 75 MHz): δ 36.6 (CH2),
42.7 (CH2), 45.6 (CH2), 55.6 (CH), 119.0 (N–C), 121.4, 122.4, 122.6,
124.8, 127.1, 128.3, 128.6, 129.0, 129.7, 132.4, 137.4, 138.3 (ArC),
139.2 (N–C), 147.4 (N=C), 153.7 (N=C), 158.5 (C=O); ESI-MS m/z:
687.33 (M+H)+. Anal. Calcd for C44H34N10O2: C, 71.92; H, 4.66; N,
19.06. Found: C, 71.87; H, 4.80; N, 19.13%.
4k
4l
4-ClC6H4
4-ClC6H4
4-ClC6H4
H
2-Me
Ph
87
82
75
4m
4n
4-ClC6H4
73
a Isolated yields based on iminophosphorane 1.
1,4-Bis[6,9-dihydro-6-oxo-1,9-diphenyl-1H-purin-2-yl]-2-(thio-
phen-2-yl)-piperazine (4e): White crystals; m.p. 261–263 °C; IR
(KBr): 3342, 2936, 1696 (C=O), 1576, 1374 cm−1; 1H NMR (CDCl3,
300 MHz): δ 2.68 (t, J = 7.2 Hz, 4H, CH2), 2.97 (d, J = 7.2 Hz, 2H,
CH2), 4.13 (t, J = 7.2 Hz, 1H, CH), 6.56–6.97 (m, 3H, thiophene-H),
7. 3 (s, 2H, ArH), 7.24–7.65 (m, 18H, ArH), 7.96 (s, 2H, imidazole-
H); 13C NMR(CDCl3, 75 MHz): δ 37.5 (CH2), 42.7 (CH2), 45.6 (CH2),
54.0 (CH), 119.0 (N–C), 121.4, 122.4, 122.6, 123.6, 124.8, 126.7,
126.9, 127.1, 127.8, 128.3, 128.6, 129.0, 129.7, 132.4, 137.4, 138.3
(ArC), 139.2 (N–C), 147.4 (N=C), 153.7 (N=C), 158.5 (C=O);
ESI-MS m/z: 741.36 (M+H)+. Anal. Calcd for C42H32N10O2S: C, 68.09;
H, 4.35; N, 18.91. Found: C, 67.98; H, 4.38; N, 18.85%.
1,4-Bis[6,9-dihydro-6-oxo-1-(4-methylphenyl)-9-phenyl-1H-purin-
2-yl]piperazine (4f): White crystals; m.p. 274–276 °C; IR (KBr):
3328, 2915, 1688 (C=O), 1508, 1119 cm−1; 1H NMR (CDCl3,
300 MHz): δ 2.33 (s, 6H, 2CH3), 2.65 (t, J = 7.2 Hz, 8H, 4CH2),
7.12–7.50 (m, 18H,ArH), 7.96 (s, 2H, imidazole-H); 13C NMR(CDCl3,
75 MHz): δ 24.3 (CH3), 45.3 (CH2), 119.0 (N–C), 121.5, 122.4, 122.6,
128.3, 129.3, 129.6, 129.8, 134.0, 137.0 (ArC), 137.8 (N–C), 147.5
(N=C), 154.5 (N=C), 158.6 (C=O); ESI-MS m/z: 687.34 (M+H)+.
Anal. Calcd for C40H34N10O2: C, 69.96; H, 4.99; N, 20.40. Found: C,
69.81; H, 4.83; N, 20.28%.
1,4-Bis[6,9-dihydro-6-oxo-1-(4-methylphenyl)-9-phenyl-1H-purin-
2-yl]-2-methylpiperazine (4g): White crystals; m.p. 287–2288 °C; IR
(KBr): 3327, 2935, 1689 (C=O), 1486, 1138 cm−1; 1H NMR (CDCl3,
300 MHz): δ 1.11 (d, J = 6.4 Hz, 3H, CH3), 2.35 (s, 6H, 2CH3), 2.62
(d, J = 7.2 Hz, 2H, CH2), 2.76(t, J = 7.2 Hz, 4H, 2CH2), 3.03 (m, 1H,
CH), 7.06–7.58 (m, 18H, ArH), 7.96 (s, 2H, imidazole-H); 13C
NMR(CDCl3, 75 MHz): δ 16.3 (CH3), 24.3 (CH3), 42.8 (CH2), 44.1
(CH2), 45.6 (CH2), 46.6 (CH), 119.0 (N–C), 121.5, 122.4, 128.3,
129.3, 129.8, 134.0, 137.4 (ArC), 137.8 (N–C), 148.9 (N=C), 151.6
(N=C), 161.6 (C=O); ESI-MS m/z: 701.27 (M+H)+. Anal. Calcd for
C41H36N10O2: C, 70.27; H, 5.18; N, 19.99. Found: C, 70.13; H, 5.28; N,
20.06%.
1,4-Bis[6,9-dihydro-6-oxo-1-(4-methylphenyl)-9-phenyl-1H-purin-
2-yl]-2,5-dimethylpiperazine (4h): White crystals; m.p. > 300 °C; IR
(KBr): 3342, 1701 (C=O), 1557, 1423, 1118 cm−1; 1H NMR (CDCl3,
300 MHz): δ 1.11 (d, J = 7.0 Hz, 6H, 2CH3), 2.35 (s, 6H, 2CH3), 2.63
(d, J = 7.2 Hz, 4H, 2CH2), 3.04 (m, 2H, 2CH), 7.06–7.53 (m, 18H,
ArH), 7.97 (s, 2H, imidazole-H); 13C NMR(CDCl3, 75 MHz): δ 16.3
(CH3), 24.3 (CH3), 41.6 (CH2), 46.9 (CH), 119.0 (N–C), 121.5, 122.4,
128.3, 129.3, 129.8, 134.0, 137.4 (ArC), 137.8 (N–C), 148.9 (N=C),
151.6 (N=C), 161.6 (C=O); ESI-MS m/z: 715.43 (M+H)+. Anal. Calcd
for C42H38N10O2: C, 70.57; H, 5.36; N, 19.59. Found: C, 70.63; H,
5.46; N, 19.71%.
Experimental
Melting points were determined using an X-4 model apparatus and
were uncorrected. IR spectra were recorded on a Nicolet 7500 NXR
IR spectrometer as KBr pellets with absorption given in cm−1. H
1
NMR spectra were recorded in CDCl3 on a Varian Mercury Plus 300
(300 MHz) spectrometer and chemical shifts (δ) were given in ppm
using (CH3)4Si as an internal reference (δ = 0). Mass spectral (MS)
data were obtained on a Finnigan LCQ Advantage MAX mass spec-
trometer. Elementary analyses were taken on a Perkin-Elmer CHN
2400 elemental analysis instrument. All reagents and solvents used in
this work were available commercially and were used as received,
unless otherwise indicated.
Synthesis of 1,4-bis[6-oxo-9-phenyl-1H-purin-2-yl]piperazines 4;
general procedure
Aromatic isocyanate (0.006 mol) was added to the solution of imino-
phosphorane 1 (0.006 mol) in THF (10 mL) at 0–5 °C. When the
resulting iminophosphorane 1 reacted with an aromatic isocyanate,
triphenylphosphine oxide was formed. The reaction mixture was left
unstirred for 5–6 h at 0–5 °C and then the solvent was removed under
reduced pressure and Et2O/petroleum ether (1:2, 12 mL) was added to
precipitate triphenylphosphine oxide. Removal of the solvent gave
carbodiimides 2, which were used directly without further purifica-
tion. A piperazine derivative (0.003 mol) was added to the solution of
2 prepared as above in CH2Cl2 (10 mL) to give intermediate guanidines
3. The reaction mixture was left unstirred for 2–3 h, the solvent was
removed and EtONa in anhydrous EtOH (8 mL, 10%) was added. The
mixture was stirred for 1–1.5 h at room temperature. The solution was
condensed and the residue was recrystallised from EtOH to give the
target compound 4. TLC was used to follow the progress of all the
above reactions.
1,4-Bis[6,9-dihydro-6-oxo-1,9-diphenyl-1H-purin-2-yl]piperazine
(4a): White crystals; m.p. 231–233 °C; IR (KBr): 3327, 1698 (C=O),
1507, 1436, 1119 cm−1; H NMR (CDCl3, 300 MHz): δ 2.67 (t, J =
1
7.2 Hz, 8H, 4CH2), 7.03 (s, 2H, ArH), 7.22–7.65 (m, 18H, ArH),
7.89 (s, 2H, imidazole-H); 13C NMR(CDCl3, 75 MHz): δ 45.3 (CH2),
119.0 (N–C), 121.4, 122.1, 122.6, 124.8, 128.3, 129.0, 129.7, 132.4,
136.1(ArC), 137.8 (N–C), 148.9 (N=C), 151.2 (N=C), 160.2 (C=O);
ESI-MS m/z: 659.24 (M+H)+. Anal. Calcd for C38H30N10O2: C, 69.29;
H, 4.59; N, 21.26. Found: C, 69.21; H, 4.73; N 21.37%.
1,4-Bis[6,9-dihydro-6-oxo-1,9-diphenyl-1H-purin-2-yl]-2-methyl-
piperazine (4b): White crystals; m.p. 255–256 °C; IR (KBr): 3342,
1709 (C=O), 1514, 1426, 1118 cm−1; H NMR (CDCl3, 300 MHz):
1
δ 1.05 (d, J = 6.8 Hz, 3H, CH3), 2.52 (d, J = 7.2 Hz, 2H, CH2), 2.63 (t,
J = 7.2 Hz, 2H, CH2), 2.76 (t, J = 7.2 Hz, 2H, CH2), 3.08 (m, 1H, CH),
7.00 (s, 2H, ArH), 7.24–7.64 (m, 18H, ArH), 7.97 (s, 2H, imidazole-
H); 13C NMR(CDCl3, 75 MHz): δ 16.3 (CH3), 42.8 (CH2), 44.2 (CH2),
1,4-Bis[6,9-dihydro-6-oxo-1-(4-methylphenyl)-9-phenyl-1H-purin-
2-yl]-2-(thiophen-2-yl)-piperazine (4i): White crystals; m.p. 267–
1
279 °C; IR (KBr): 3305, 1707 (C=O), 1517, 1465, 1118 cm−1; H

JOURNAL OF CHEMICAL RESEARCH 2012 705
NMR (CDCl3, 300 MHz): δ 2.35 (s, 6H, 2CH3), 2.67 (t, J = 7.2 Hz,
4H, 2CH2), 3.04 (d, J = 6.8 Hz, 2H, 2CH), 4.15 (t, J = 7.0 Hz, 1H,
CH), 6.60–6.92 (m, 3H, thiophene-H), 7.06–7.52 (m, 18H, ArH), 7.97
(s, 2H, imidazole-H); 13C NMR(CDCl3, 75 MHz): δ 24.3 (CH3), 37.3
(CH2), 42.6 (CH2), 45.6 (CH2), 54.3 (CH), 119.0 (N–C), 121.5, 122.4,
123.6, 126.7, 126.9, 127.8, 128.3, 129.3, 129.8, 134.0, 137.4 (ArC),
137.8 (N–C), 148.7 (N=C), 153.3 (N=C), 159.5 (C=O); ESI-MS m/z:
769.37 (M+H)+. Anal. Calcd for C44H36N10O2S: C, 68.73; H, 4.72; N,
18.22. Found: C, 68.65; H, 4.66; N, 18.15%.
1,4-Bis[6,9-dihydro-6-oxo-1-(4-methylphenyl)-9-phenyl-1H-purin-
2-yl]-2-(furan-2-yl)-piperazine (4j): White crystals; m.p.> 300 °C; IR
(KBr): 3324, 2906, 1695 (C=O), 1443, 1324 cm−1; 1H NMR (CDCl3,
300 MHz): δ 2.35 (s, 6H, 2CH3), 2.68 (d, J = 7.2 Hz, 4H, 2CH2), 2.96
(d, J = 6.8 Hz, 2H, CH2), 4.38 (t, J = 7.0 Hz, 1H, CH), 6.07–6.24
(m, 2H, furan-H), 7.04–7.52 (m, 19H, ArH and furan-H), 7.97 (s, 2H,
imidazole-H); 13C NMR(CDCl3, 75 MHz): δ 24.3 (CH3), 34.8 (CH2),
40.3 (CH2), 45.1 (CH2), 54.5 (CH), 119.0 (N–C), 105.8, 110.0, 121.5,
122.4, 123.6, 126.7, 126.9, 127.8, 128.3, 129.3, 129.8, 134.0, 137.4
(ArC), 137.8 (N–C), 148.5 (N=C), 155.9 (N=C), 161.3 (C=O);
ESI-MS m/z: 753.34 (M+H)+. Anal. Calcd for C44H36N10O3: C, 70.20;
H, 4.82; N, 18.61. Found: C, 70.03; H, 4.75; N, 18.70%.
128.3, 128.8, 129.1, 129.7, 129.9, 130.8, 137.3, 138.3 (ArC), 137.8
(N–C), 144.3 (N–C), 147.8 (N=C), 152.8 (N=C), 159.6 (C=O); ESI-
MS m/z: 803.21 (M+H)+. Anal. Calcd for C44H32N10O2Cl2: C, 65.76; H,
4.01; N, 17.43. Found: C, 65.82; H, 3.91; N, 17.38%.
1,4-Bis[6,9-dihydro-6-oxo-1-(4-chlorophenyl)-9-phenyl-1H-purin-
2-yl]-2-(thiophen-2-yl)-piperazine (4n): White crystals; m.p. 295–
1
297 °C; IR (KBr): 3311, 2927, 1707 (C=O), 1540, 1438 cm−1; H
NMR (CDCl3, 300 MHz): δ 2.75 (t, J = 7.2 Hz, 4H, 2CH2), 2.91 (d,
J = 7.2 Hz, 2H, CH2), 3.04 (t, J = 6.8 Hz, 1H, CH), 6.66–6.90 (m, 3H,
thiophene-H), 7.25–7.58 (m, 18H, ArH), 7.97 (s, 2H, imidazole-H);
13C NMR(CDCl3, 75 MHz): δ 37.5 (CH3), 42.7 (CH2), 45.6, 54.6
(CH), 119.0 (N–C), 122.4, 123.0, 123.6, 126.7, 126.9, 127.1, 127.8,
128.0, 128.3, 128.8, 129.1, 129.7, 129.9, 130.8, 137.3, 138.3 (ArC),
137.8 (N–C), 143.6 (N–C), 147.8 (N=C), 152.8 (N=C), 160.3 (C=O);
ESI-MS m/z: 809.28 (M+H)+. Anal. Calcd for C42H30N10O2SCl2: C,
62.30; H, 3.73; N, 17.30. Found: C, 62.27; H, 3.62; N, 17.17.
Received 12 September 2012; accepted 6 October 2012
Paper 1201513 doi: 10.3184/174751912X13505755737168
Published online: 5 December 2012
1,4-Bis[6,9-dihydro-6-oxo-1-(4-chlorophenyl)-9-phenyl-1H-purin-
2-yl]piperazine (4k): White crystals; m.p. 255–256 °C; IR (KBr):
3302, 1688 (C=O), 1561, 1477, 1211 cm−1; 1H NMR (CDCl3,
300 MHz): δ 2.67 (t, J = 7.2 Hz, 8H, 4CH2), 7.25–7.57 (m, 18H, ArH),
7.97 (s, 2H, imidazole-H); 13C NMR(CDCl3, 75 MHz): δ 45.3 (CH2),
119.0 (N–C), 122.4, 123.0, 128.3, 129.1, 129.7, 129.9, 130.8, 137.3
(ArC), 137.8 (N–C), 148.5 (N=C), 152.7 (N=C), 158.6 (C=O);
ESI-MS m/z: 727.39 (M+H)+. Anal. Calcd for C38H28N10O2Cl2: C,
62.73; H, 3.88; N, 19.25. Found: C, 62.64; H, 3.76; N, 19.19%.
1,4-Bis[6,9-dihydro-6-oxo-1-(4-chlorophenyl)-9-phenyl-1H-purin-
2-yl]-2-methylpiperazine (4l): White crystals; m.p. 277–279 °C; IR
(KBr): 3305, 1689 (C=O), 1557, 1434, 1118 cm−1; 1H NMR (CDCl3,
300 MHz): δ 1.06 (d, J = 6.8 Hz, 3H, CH3), 2.63 (d, J = 7.2 Hz, 2H,
CH2), 2.72 (t, J = 7.2 Hz, 4H, 2CH2), 3.05 (m, 1H, CH), 7.26–7.58
(m, 18H,ArH), 7.97 (s, 2H, imidazole-H); 13C NMR(CDCl3, 75 MHz):
δ 16.3 (CH3), 42.8 (CH2), 44.1 (CH2), 45.6 (CH2), 46.6 (CH), 119.0
(N–C), 122.4, 123.0, 128.3, 129.1, 129.7, 129.9, 130.8, 137.3 (ArC),
137.8 (N–C), 144.3 (N–C), 147.8 (N=C), 153.3 (N=C), 159.2 (C=O);
ESI-MS m/z: 741.25 (M+H)+. Anal. Calcd for C39H30N10O2Cl2: C,
63.16; H, 4.08; N, 18.89. Found: C, 63.08; H, 4.11; N, 18.85%.
1,4-Bis[6,9-dihydro-6-oxo-1-(4-chlorophenyl)-9-phenyl-1H-purin-
2-yl]-2-phenylpiperazine (4m): White crystals; m.p. > 300 °C; IR
(KBr): 3313, 1689 (C=O), 1453, 1212 cm−1; 1H NMR (CDCl3,
300 MHz): δ 2.66 (t, J = 7.2 Hz, 4H, 2CH2), 3.04 (d, J = 6.8 Hz, 2H,
CH2), 4.15 (t, J = 7.0 Hz, 1H, CH), 7.12–7.58 (m, 23H, ArH), 7.97
(s, 2H, imidazole-H); 13C NMR(CDCl3, 75 MHz): δ 36.3 (CH3), 42.7
(CH2), 45.6 55.8 (CH), 119.0 (N–C), 122.4, 123.0, 127.1, 128.0,
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