Iminophosphorane-mediated efficient synthesis of new tricyclic 3,5-dihydro-1,2,3-triazolo[4,5-d]-1,2,4-triazolo[1,5-a]pyrimidin-9-ones

Article abstract of DOI:10.1039/b513715b

The carbodiimides 2, obtained from aza-Wittig reactions of iminophosphorane 1 with aromatic isocyanates, reacted with hydrazine to give selectively 6-amino-7H-1,2,3-triazolo[4,5-d]pyrimidin-7-ones 5. Compounds 5 were further transformed to iminophosphoran

Full text of DOI:10.1039/b513715b

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Iminophosphorane-mediated efficient synthesis of new tricyclic
3,5-dihydro-1,2,3-triazolo[4,5-d]-1,2,4-triazolo[1,5-a]pyrimidin-9-ones
Jun-Feng Zhao, Chang Xie, Sheng-Zhen Xu, Ming-Wu Ding* and Wen-Jing Xiao*
Received 27th September 2005, Accepted 8th November 2005
First published as an Advance Article on the web 28th November 2005
DOI: 10.1039/b513715b
The carbodiimides 2, obtained from aza-Wittig reactions of iminophosphorane 1 with aromatic
isocyanates, reacted with hydrazine to give selectively 6-amino-7H-1,2,3-triazolo[4,5-d]pyrimidin-
7-ones 5. Compounds 5 were further transformed to iminophosphoranes 6 by reaction with triphenyl-
phosphine, hexachloroethane and triethylamine. A tandem aza-Wittig reaction of iminophosphorane 6
with isocyanate or acyl chloride generated previously unreported 3,5-dihydro-1,2,3-triazolo[4,5-d]-
1,2,4-triazolo[1,5-a]pyrimidin-9-ones 10 or 12 in satisfactory yield. X-ray structure analysis of 10g
verified the proposed structure and the reaction selectivity.
Table 1 Preparation of compounds 5 or 6
Introduction
Ar1
Ar2
Yield (%)a
7H-1,2,3-Triazolo[4,5-d]pyrimidin-7-ones (azaguanines) are of
great importance because of their structural similarity with
guanines. Some derivatives of them have shown remarkable bi-
ological (antiguanine) properties such as antitumor, antiviral, and
anti-HIV activities,1–5 whereas others exhibited good fungicidal
activities.6 On the other hand, heterocycles containing the 1,2,4-
triazole nucleus also exhibit various biological activities; several
of them have been used as fungicidal, bactericidal, insecticidal,
antitumor and anti-inflammatory agents.7–13 The introduction
of a triazole ring to the triazolo[4,5-d]pyrimidin-7-one system
is expected to influence the biological activities significantly.
However, this tricyclic system has been much less investigated and
there is no report on synthesis of 3,5-dihydro-1,2,3-triazolo[4,5-
d]-1,2,4-triazolo[1,5-a]pyrimidin-9-ones.
5a
5b
5c
6a
6b
6c
Ph
Ph
Ph
Ph
Ph
Ph
Ph
91
86
84
88
90
90
4-ClC6H4
4-MeC6H4
Ph
4-ClC6H4
4-MeC6H4
a Isolated yields based on iminophosphorane 1.
Recently we have been interested in the synthesis of quinazoli-
nones, thienopyrimidinones and imidazolinones via aza-Wittig re-
action of a or b ethoxycarbonyl iminophosphorane with aromatic
isocyanate and subsequent reaction with various nucleophiles
under mild conditions.14–18 Here we wish to report an efficient
approach to the synthesis of previously unreported 3,5-dihydro-
1,2,3-triazolo[4,5-d]-1,2,4-triazolo[1,5-a]pyrimidin-9-ones by
tandem iminophosphorane-mediated annulation of easily acces-
sible N-(5-arylamino-7H-1,2,3-triazolo[4,5-d]pyrimidin-7-on-6-
yl)iminotriphenylphosphorane with isocyanates or acyl chloride.
Results and discussion
Iminophosphorane 119 reacted with aromatic isocyanates to give
carbodiimides 2, which were allowed to react with hydrazine to
give selectively 6-amino-7H-1,2,3-triazolo[4,5-d]pyrimidin-7-ones
5 in 72–81% yields (Scheme 1, Table 1). No formation of the
potential regioisomer 4 was observed. It is worth noting that
the reaction of b ethoxycarbonyl carbodiimide with hydrazine
seems to be controversial. Our recent result on reaction of b-
Scheme 1 Synthesis of compounds 5 and 6. (a) Ar2NCO, CH2Cl2, 0–5 ◦C,
24–30 h; (b) NH2NH2·H2O, CH3CN, rt, 10–20 min; (c) PPh3, C2Cl6, NEt3,
CH2Cl2, rt, 4–6 h.
ethoxycarbonyl phenylcarbodiimide with hydrazine gave selec-
tively 3-aminoquinazolin-4(3H)-one,20 consistent with formation
of 5. However, an early report on a similar reaction using carbodi-
imide 7 resulted in the formation of 2-hydrazinopyrimidinone 8,
another possible regioisomer (Scheme 2).19 The selective formation
Key Laboratory of Pesticide & Chemical Biology, Ministry of Education,
College of Chemistry, Central China Normal University, Wuhan, 430079,
P. R. China. E-mail: mwding@mail.ccnu.edu.cn
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which easily undergoes ring closure across the arylamino group
to give the otherwise not readily available 6-arylamino substituted
1,2,3-triazolo[4,5-d]-1,2,4-triazolo[1,5-a]pyrimidin-9-ones 10. It is
noteworthy that the reaction can be easily carried out at refluxing
temperature (CH2Cl2 as solvent) under mild neutral condition
and the separation of 10 from the reaction mixture was also easily
carried out by simple filtration.
Iminophosphoranes 6 reacted with acyl chlorides in the presence
of triethylamine in methylene chloride at refluxing tempera-
ture to give 6-substituted 1,2,3-triazolo[4,5-d]-1,2,4-triazolo[1,5-
a]pyrimidin-9-ones 12 in good yields (73–86%, Table 2, Scheme 4).
The formation of 12 can be viewed as an initial aza-Wittig reaction
between the iminophosphorane 6 and acyl chloride in presence of
triethylamine affording the intermediate imidoyl chloride 11 which
undergoes cyclization to give 12.
Scheme 2 Literature synthesis of compounds 8 from carbodiimide 7.
(a) NH2NH2·H2O, EtOH, rt, 3 h.
of 5 can be rationalized in terms of an initial nucleophilic addition
of hydrazine to give the guanidine intermediate 3 which directly
cyclizes to give 5 across the strong nucleophilic hydrazine group
rather than the arylamine one.21
Compounds 5 were easily converted to novel functional-
ized iminophosphoranes 6 via reaction with triphenylphosphine,
hexachloroethane and triethylamine in good yields (88–90%,
Scheme 1, Table 1). When solutions of iminophosphoranes 6 in
dry methylene chloride were treated with aromatic isocyanate at re-
fluxing temperature, the previously unreported 6-arylamino-1,2,3-
triazolo[4,5-d]-1,2,4-triazolo[1,5-a]pyrimidin-9-ones 10 were iso-
lated as crystalline solids in good yields (78–91%, Table 2,
Scheme 3). Presumably, the conversion of 6 into 10 involves initial
aza-Wittig reaction between the iminophosphorane 6 and the
isocyanate to give a carbodiimide 9 as highly reactive intermediate,
Scheme 4 Synthesis of compounds 12 (a) RCOCl, CH2Cl2, NEt3, 40 ◦C,
2–4 h.
The structure of 3,5-dihydro-1,2,3-triazolo[4,5-d]-1,2,4-tri-
azolo[1,5-a]pyrimidin-9-ones 10 and 12 was confirmed by their
spectral data. Furthermore a single crystal of 10g was obtained
from a DMF solution of 10g. X-ray structure analysis verified
again the proposed structure, and showed that all ring atoms in the
tricyclic moiety are essentially planar, with the maxim deviation of
˚
0.0392 A for N(2) from the heterocyclic plane (Fig. 1). The bond
˚
=
=
=
=
lengths of C(4) N(4), C(5) N(6), and C(1) C(2) are 1.307(3) A,
Scheme 3 Preparation of tricyclic compound 10. (a) Ar3NCO, CH2Cl2,
˚
˚
40 ◦C, 1–2 h.
1.311(3) A and 1.386(3) A, are longer than that of the typical C N
˚
˚
=
(1.28 A) and C C (1.34 A) bonds respectively, while the single
bond lengths of C(1)–N(1), C(2)–N(3), C(1)–N(4), C(4)–N(5),
Table 2 Preparation of compounds 10a–h or 12a–f
˚
C(4)–N(7), N(7)–C(5) and C(2)–C(3) are 1.354(3) A, 1.371(3)
Ar2
Ar3
R
Yield (%)a
˚
˚
˚
˚
˚
˚
A, 1.361(3) A, 1.370(3) A, 1.368(3) A, 1.389(3) A and 1.435(3)
A respectively, are significantly shorter than the typical C(sp )–
2
10a
10b
10c
10d
10e
10f
10g
10h
12a
12b
12c
12d
12e
12f
Ph
Ph
Ph
4-ClC6H4
Ph
4-ClC6H4
4-MeC6H4
3-MeC6H4
Ph
91
84
78
90
83
84
82
87
78
84
86
73
75
85
˚
˚
N(1.426 A) and C–C(1.53 A), showing a degree of delocalization.
In conclusion, we have developed an efficient iminophospho-
rane-mediated synthesis of previously unreported 3,5-dihydro-
1,2,3-triazolo[4,5-d ]-1,2,4-triazolo[1,5-a]pyrimidin-9-ones via
aza-Wittig reactions. The spectral and X-ray analysis of the
product verified the proposed structure and the reaction selectivity.
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-MeC6H4
4-MeC6H4
Ph
4-MeC6H4
Ph
Me
Ph
Me
Ph
Me
Ph
4-ClC6H4
4-ClC6H4
4-MeC6H4
4-MeC6H4
Experimental
General materials and methods
Reagents and chemicals were obtained from Acros, Aldrich,
Shanghai or Beijing chemicals and were used without further
a Isolated yields based on iminophosphorane 6.
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◦
mp: 253–255 C; IR (KBr) cm−1 3329, 3262 (N–H), 1718 (C O),
1542, 1203; 1H NMR (400 MHz, CDCl3) d 4.75 (s, 2H), 7.19–8.15
(m, 10H), 8.94 (s, 1H); MS m/z (%) 319 (M+, 9), 291 (2), 274 (2),
118 (18), 77 (100); Anal. Calcd for C16H13N7O: C, 60.18; H, 4.10;
N, 30.70. Found: C, 60.35; H, 4.03; N, 30.93%.
=
6-Amino-5-(4-chlorophenyl)amino-3,6-dihydro-3-phenyl-7H-1,2,3-
triazolo[4,5-d]pyrimidin-7-one (5b). White crystals (607 mg, 86%
◦
yield), mp: >300 C; IR (KBr) cm−1 3309, 3263 (N–H), 1716
1
=
(C O), 1559, 1204; H NMR (400 MHz, DMSO-d6) d 5.75 (s,
2H), 7.43–8.04 (m, 9H), 10.01 (s, 1H); MS m/z (%) 355/353 (M+,
15/45), 325 (12), 309 (5), 111 (23), 77 (100); Anal. Calcd for
C16H12ClN7O: C, 54.32; H, 3.42; N, 27.71. Found: C, 54.47; H,
3.64; N, 27.57%.
6-Amino-3,6-dihydro-5-(4-methylphenyl)amino-3-phenyl-7H-
1,2,3-triazolo[4,5-d]pyrimi◦din-7-one (5c). White crystals (560 mg,
Fig. 1 ORTEP diagram of the crystal structure of tricyclic compound
10g (50% thermal ellipsoids). For clarity, solvent molecular (DMF)
and all hydrogen atoms have been omitted. Select bond lengths [A]:
84% yield), mp: 253–255 C; IR (KBr) cm−1 3314, 3260 (N–H),
1
=
1701 (C O), 1556, 1205; H NMR (400 MHz, DMSO-d6) d 2.30
˚
(s, 3H), 5.74 (s, 2H), 7.18–8.07 (m, 9H), 9.80 (s, 1H); MS m/z (%)
333 (M+, 57), 305 (19), 289 (15), 131 (26), 77 (100); Anal. Calcd
for C17H15N7O: C, 61.25; H, 4.54; N, 29.41. Found: C, 61.08; H,
4.69; N, 29.64%.
C(1)–N(1) 1.354(3), N(1)–N(2) 1.377(3), N(2)–N(3) 1.304(3), C(2)–N(3)
1.371(3), C(1)–C(2) 1.386(3), C(2)–C(3) 1.435(3), C(3)–N(5) 1.420(3),
C(4)–N(5) 1.370(3), C(4)–N(4) 1.307(3), C(1)–N(4) 1.361(3), N(5)–N(6)
1.403(3), C(5)–N(6) 1.311(3), C(5)–N(7) 1.389(3), C(4)–N(7) 1.368(3),
C(3)–O(1) 1.211(3), C(5)–N(8) 1.347(3), C(6)–N(8) 1.414(3). Selected
bond angles [deg]: N(3)–N(2)–N(1) 108.3(2), C(1)–N(1)–N(2) 109.8(2),
N(1)–C(1)–C(2) 104.5(2), N(2)–N(1)–C(19) 120.9(2), C(1)–C(2)–C(3)
121.7(2), N(5)–C(3)–C(2) 107.5(2), C(4)–N(5)–C(3) 124.9(2), N(4)–C(4)–
N(5) 128.5(2), C(4)–N(4)–C(1) 108.3(2), N(4)–C(1)–C(2) 129.0(2),
C(4)–N(5)–N(6) 112.23(18), C(5)–N(6)–N(5) 103.03(19), N(6)–C(5)–N(7)
112.9(2), C(4)–N(7)–C(5) 107.0(2), N(7)–C(4)–N(5) 104.8(2), C(4)–N(7)–
C(12) 123.9(2).†
5-Arylamino-6-(triphenylphosphoranylidene)amino-7H-
1,2,3-triazolo[4,5-d]pyrimidin-7-ones (6)
To a mixture of 5 (8 mmol), PPh3 (3.14 g, 12 mmol) and C2Cl6
(2.84 g, 12 mmol) in dry CH2Cl2 (40 mL), was added dropwise
NEt3 (2.42 g, 24 mmol) at room temperature. The colour of the
reaction mixture quickly turned yellow. After being stirred for
4–6 h, the solvent was removed under reduced pressure and the
residue was recrystallized from EtOH to give iminophosphorane 6.
purification. All solvents were freshly distilled. Melting points
are uncorrected. MS were measured on a Finnigan Trace MS
spectrometer. IR were recorded on a PE-983 infrared spectrometer
as KBr pellets with absorption in cm−1. NMR were recorded in
CDCl3 or DMSO-d6 on a Varian Mercury 400 spectrometer and
resonances are given in ppm (d) relative to TMS. Elementary
analyses were taken on a Vario EL III elementary analysis
instrument.
3,6-Dihydro-3-phenyl-5-phenylamino-6-(triphenylphosphoranyl-
idene)amino-7H-1,2,3-triazolo[4,5-d]pyrimidin-7-one (6a). White
crystals (4.07 g, yield 88%), mp: 278–280 ◦C; IR (KBr) cm−1: 3264
1
=
(N–H), 1699 (C O), 1550, 1110; H NMR (CDCl3, 400 MHz) d:
7.12–8.18 (m, 25H), 9.90 (s, 1H); MS m/z (%) 579 (M+, 62), 551
(8), 262 (74), 183 (83), 77 (100); Anal. Calcd for C34H26N7OP: C,
70.46; H, 4.52; N, 16.92. Found: C, 70.68; H, 4.37; N, 16.75%.
5-Arylamino-6-amino-7H-1,2,3-triazolo[4,5-d]pyrimidin-7-ones (5)
To a solution of iminophosphorane 16 (2 mmol) in dry methylene
chloride (15 mL) was added aromatic isocyanate (2 mmol) under
nitrogen at room temperature. After the reaction mixture was
stood for 24–30 hours at 0–5 ◦C, the solvent was removed off
under reduced pressure and ether–petroleum ether (1:2, 20 mL)
was added to precipitate triphenylphosphine oxide. After filtration
the solvent was removed to give carbodiimide 2, which was used
directly without further purification. To the solution of 2 prepared
above in CH3CN (15 ml) was added hydrazine hydrate (0.24 g,
4 mmol, 85%) in EtOH (5 mL). The mixture was stirred for 10 min
at room temperature and filtered to give 5-arylamino-6-amino-
7H-1,2,3-triazolo[4,5-d]pyrimidin-7-ones 5.
5-(4-Chlorophenyl)amino-3,6-dihydro-3-phenyl-6-(triphenylphos-
phoranylidene)amino-7H-1,2,3-triazolo[4,5-d]pyrimidin-7-one (6b).
White crystals (4.42 g, yield 90%), mp: 287–288 ◦C; IR (KBr) cm−1:
3305 (N–H), 1701 (C O), 1549, 1107; 1H NMR (CDCl3,
=
400 MHz) d: 7.26–8.14 (m, 24H), 9.93 (s, 1H); MS m/z (%)
615/613 (M+, 3/9), 276 (16), 262 (24), 183 (78), 77 (100); Anal.
Calcd for C34H25ClN7OP: C, 66.51; H, 4.10; N, 15.97. Found: C,
66.35; H, 4.35; N, 15.84%.
3,6-Dihydro-5-(4-methylphenyl)amino-3-phenyl-6-(triphenylphos-
phoranylidene)amino-7H-1,2,3-triazolo[4,5-d]pyrimidin-7-one (6c).
White crystals (4.26 g, yield 90%), mp: >300 ◦C; IR (KBr) cm−1:
3276 (N–H), 1699 (C O), 1557, 1107; 1H NMR (CDCl3,
6-Amino-3,6-dihydro-3-phenyl-5-phenylamino-7H-1,2,3-triazolo-
[4,5-d]pyrimidin-7-one (5a). White crystals (580 mg, 91% yield),
=
400 MHz) d: 2.36 (s, 3H), 7.17–8.19 (m, 24H), 9.79 (s, 1H);
MS m/z (%) 593 (M+, 28), 304 (40), 262 (60), 183 (100), 77 (95);
Anal. Calcd for C35H28N7OP: C, 70.82; H, 4.75; N, 16.52. Found:
C, 70.75; H, 4.76; N, 16.68%.
† CCDC reference number 279775. For crystallographic data in CIF or
other electronic format see DOI: 10.1039/b513715b
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6-Arylamino-1,2,3-triazolo[4,5-d]-1,2,4-triazolo[1,5-a]pyrimidin-
9-one (10)
(26), 77 (100); Anal. Calcd for C24H17ClN8O: C, 61.48; H, 3.65;
N, 23.90. Found: C, 61.41; H, 3.78; N, 23.84%.
3,5-Dihydro-5-(4-methylphenyl)-3-phenyl-6-phenylamino-1,2,3-
To a solution of iminophosphorane 6 (1 mmol) in dry methylene
chloride (10 mL) was added aromatic isocyanate (1 mmol) under
nitrogen at room temperature. After the solution is stirred at
refluxing temperature for 1–2 h, the white precipitated solid is
collected by filtration and recrystallized from CH2Cl2–ethanol to
give 10 as crystalline solids.
triazolo[4,5-d]-1,2,4-triazolo[1,5-a]pyrimidin-9-one (10g). White
◦
crystals (355 mg, yield 82%), mp: >300 C; IR (KBr) cm−1:
1
=
3402 (N–H), 1719 (C O), 1543, 1457; H NMR (CDCl3–TFA,
400 MHz) d: 2.54 (s, 3H), 6.88–7.82 (m, 14H); 13C NMR
(CDCl3–TFA, 100 MHz) d 21.1, 119.4, 123.0 (2), 124.4, 125.4 (2),
127.7 (2), 129.5 (2), 129.9 (2), 130.0, 130.4, 132.1 (2), 134.3, 135.6,
143.7, 147.8, 148.4, 150.3, 150.6; MS m/z (%) 434 (M+, 42), 406
(19), 288 (22), 274 (17), 77 (100); Anal. Calcd for C24H18N8O: C,
66.35; H, 4.18; N, 25.79. Found: C, 66.15; H, 4.10; N, 25.88%.
3,5-Dihydro-3,5-diphenyl-6-phenylamino-1,2,3-triazolo[4,5-d]-
1,2,4-triazolo[1,5-a]pyrimidin-9-one
(10a). White
crystals
◦
(384 mg, yield 91%), mp: >300 C; IR (KBr) cm−1: 3413 (N–H),
1720 (C O), 1544, 1399; 1H NMR (DMSO-d6, 400 MHz) d:
=
7.08–7.95 (m, 15H), 9.16 (s, 1H); 13C NMR (DMSO-d6, 100 MHz)
d 119.8, 123.5 (2), 124.6, 125.7 (2), 127.8 (2), 129.5 (2), 129.8 (2),
130.2, 130.4, 132.3 (2), 134.1, 134.9, 135.8, 147.7, 148.3, 150.2,
150.4; MS m/z (%) 420 (M+, 26), 392 (10), 260 (14), 245 (16), 77
(100); Anal. Calcd for C23H16N8O: C, 65.71; H, 3.84; N, 26.65.
Found: C, 65.94; H, 3.97; N, 26.58%.
3,5-Dihydro-5-(4-methylphenyl)-3-phenyl-6-(4-methylphenyl)-
amino-1,2,3-triazolo[4,5-d]-1,2,4-triazolo[1,5-a]pyrimidin-9-one
(10h). White crystals (390 mg, yield 87%), mp: >300 ◦C; IR
−1
(KBr) cm : 3411 (N–H), 1717 (C O), 1545, 1510; 1H NMR
=
(CDCl3–TFA, 400 MHz) d: 2.15 (s, 3H), 2.54 (s, 3H), 6.70–7.82
(m, 13H); 13C NMR (CDCl3–TFA, 100 MHz) d 20.6, 21.1, 122.8
(2), 124.1, 125.3 (2), 127.5 (2), 128.4, 129.2 (2), 129.7 (2), 129.8,
130.2, 132.0 (2), 134.0, 135.5, 143.8, 147.7, 148.2, 150.1, 150.4;
MS m/z (%) 448 (M+, 42), 420 (19), 288 (40), 273 (16), 91 (100).
Anal. Calcd for C25H20N8O: C, 66.95; H, 4.49; N, 24.98; Found:
C, 66.84; H, 4.57; N, 25.05%.
6-(4-Chlorophenyl)amino-3,5-dihydro-3,5-diphenyl-1,2,3-triazolo-
[4,5-d]-1,2,4-triazolo[1,5-a]pyrimidin-9-one (10b). White crystals
◦
(381 mg, yield 84%), mp: >300 C; IR (KBr) cm−1: 3403 (N–H),
1721 (C O), 1544, 1493; 1H NMR (DMSO-d6, 400 MHz) d:
=
7.42–7.94 (m, 14H), 9.30 (s, 1H); MS m/z (%) 456/454 (M+, 3/9),
426 (6), 274 (13), 258 (10), 77 (100); Anal. Calcd for C23H15ClN8O:
C, 60.73; H, 3.32; N, 24.63. Found: C, 60.65; H, 3.35; N, 24.52%.
1,2,3-Triazolo[4,5-d]-1,2,4-triazolo[1,5-a]pyrimidin-9-one (12)
To a solution of iminophosphorane 6 (1 mmol) in dry CH2Cl2
(10 mL) was added acyl chloride (1 mmol) and triethylamine
(0.10 g, 1 mmol) under nitrogen at room temperature. The
solution was stirred at refluxing temperature for 2–4 h. The white
precipitated ammonium salt was separated by filtration and the
filtrate was concentrated to dryness. The residue was recrystallized
from CH2Cl2–ethanol to give 12 as crystalline solids.
5-(4-Chlorophenyl)-3,5-dihydro-3-phenyl-6-phenylamino-1,2,3-
triazolo[4,5-d]-1,2,4-triazolo[1,5-a]pyrimidin-9-one (10c). White
crystals (355 mg, yield 78%), mp: >300 ◦C; IR (KBr) cm−1: 3402
1
=
(N–H), 1721 (C O), 1540, 1492; H NMR (DMSO-d6, 400 MHz)
d: 7.08–7.94 (m, 14H), 9.16 (s, 1H); MS m/z (%) 456/454 (M+,
15/44), 426 (17), 294 (15), 273 (38), 77 (100); Anal. Calcd for
C23H15ClN8O: C, 60.73; H, 3.32; N, 24.63. Found: C, 60.87; H,
3.41; N, 24.47%.
3,5-Dihydro-3,5,6-triphenyl-1,2,3-triazolo[4,5-d]-1,2,4-triazolo-
[1,5-a]pyrimidin-9-one (12a). White crystals (316 mg, 78% yield),
◦
−1
1
5-(4-Chlorophenyl)-6-(4-chlorophenyl)amino-3,5-dihydro-3-
=
mp: >300 C; IR (KBr) cm : 1736 (C O), 1548, 1510; H NMR
(400 MHz, CDCl3) d 7.36–7.59 (m, 13H), 8.02 (d, J = 8.4 Hz,
2H); 13C NMR (CDCl3, 100 MHz) d 121.4, 123.0, 124.2, 126.7
(2), 128.4 (2), 128.6 (2), 128.8 (2), 129.2, 129.5 (2), 130.7 (2),
132.0, 132.4, 134.4, 141.0, 148.6, 150.2, 150.4, 153.2; MS m/z (%)
405 (M+, 6), 377 (5), 245 (7), 103 (30), 77 (100); Anal. Calcd for
C23H15N7O: C, 68.14; H, 3.73; N, 24.18. Found: C, 68.25; H, 3.81;
N, 24.05%.
phenyl-1,2,3-triazolo[4,5-d]-1,2,4-triazolo[1,5-a]pyrimidin-9-one
(10d). White crystals (440 mg, yield 90%), mp: >300 ◦C; IR
−1
(KBr) cm : 3407 (N–H), 1729 (C O), 1544, 1492; 1H NMR
=
(DMSO-d6, 400 MHz) d: 7.44–7.93 (m, 13H), 9.30 (s, 1H); MS
m/z (%) 492/490/488 (M+, 3/16/25), 460 (12), 308 (15), 273 (43),
77 (100); Anal. Calcd for C23H14Cl2N8O: C, 56.46; H, 2.88; N,
22.90. Found: C, 56.31; H, 2.90; N, 22.81%.
5-(4-Chlorophenyl)-3,5-dihydro-6-(4-methylphenyl)amino-3-
3,5-Dihydro-3,5-diphenyl-6-methyl-1,2,3-triazolo[4,5-d]-1,2,4-
triazolo[1,5-a]pyrimidin-9-one (12b). White crystals (289 mg,
phenyl-1,2,3-triazolo[4,5-d]-1,2,4-triazolo[1,5-a]pyrimidin-9-one
(10e). White crystals (388 mg, yield 83%), mp: >300 ◦C; IR
=
◦
−1
84% yield), mp: >300 C; IR (KBr) cm : 1743 (C O), 1557,
1498; 1H NMR (400 MHz, CDCl3–TFA) d 2.52 (s, 3H), 7.46–7.89
(m, 10H); 13C NMR (CDCl3–TFA, 100 MHz) d 11.9, 121.7 (2),
125.0, 127.0 (2), 129.0, 129.4 (2), 130.4 (2), 130.5, 131.0, 135.0,
148.4, 149.6, 150.1, 153.0; MS m/z (%) 343 (M+, 23), 315 (16),
286 (16), 245 (9), 77 (100); Anal. Calcd for C18H13N7O: C, 62.97;
H, 3.82; N, 28.56. Found: C, 62.75; H, 3.91; N, 28.36%.
−1
(KBr) cm : 3364 (N–H), 1731 (C O), 1541, 1493; 1H NMR
=
(DMSO-d6, 400 MHz) d: 2.27 (s, 3H), 7.16–7.93 (m, 13H), 9.04
(s, 1H); MS m/z (%) 470/468 (M+, 11/35), 440 (14), 308 (28), 273
(42), 77 (100); Anal. Calcd for C24H17ClN8O: C, 61.48; H, 3.65;
N, 23.90. Found: C, 61.35; H, 3.52; N, 23.97%.
5-(4-Chlorophenyl)-3,5-dihydro-6-(3-methylphenyl)amino-3-
phenyl-1,2,3-triazolo[4,5-d]-1,2,4-triazolo[1,5-a]pyrimidin-9-one
5-(4-Chlorophenyl)-3,5-dihydro-3,6-diphenyl-1,2,3-triazolo[4,5-
(10f). White crystals (393 mg, yield 84%), mp: >300 ◦C; IR
d]-1,2,4-triazolo[1,5-a]pyrimidin-9-one ◦ (12c). White crystals
−1
(KBr) cm : 3359 (N–H), 1733 (C O), 1543, 1493; 1H NMR
(377 mg, 86% yield), mp: 287–288 C; IR (KBr) cm−1 1731
=
1
=
(DMSO-d6, 400 MHz) d: 2.29 (s, 3H), 6.87–7.94 (m, 13H), 9.07
(s, 1H); MS m/z (%) 470/468 (M+, 9/28), 440 (10), 308 (17), 273
(C O), 1535, 1494; H NMR (400 MHz, CDCl3–TFA) d 7.25–
7.59 (m, 12H), 7.96 (d, J = 8.4 Hz, 2H); MS m/z (%) 441/439
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(M+, 6/20), 411 (16), 279 (22), 111 (69), 77 (100); Anal. Calcd for
C23H14ClN7O: C, 62.80; H, 3.21; N, 22.29. Found: C, 62.73; H,
3.15; N, 22.33%.
References
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and Y. Zhu, US 20020019370; V. B. Hegde, S. J. Bis, E. C. Heo, C. T.
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5-(4-Chlorophenyl)-3,5-dihydro-6-methyl-3-phenyl-1,2,3-triazolo-
[4,5-d]-1,2,4-triazolo[1,5-a]pyrim◦idin-9-one (12d). White crystals
(275 mg, 73% yield), mp: >300 C; IR (KBr) cm−1 1740 (C O),
1554, 1509; H NMR (400 MHz, CDCl3/TFA) d 2.49 (s, 3H),
=
1
7.42–7.92 (m, 10H); MS m/z (%) 379/377 (M+, 8/27), 349 (19),
320 (19), 273 (21), 111 (100); Anal. Calcd for C18H12ClN7O: C,
57.23; H, 3.20; N, 25.95. Found: C, 57.47; H, 3.15; N, 25.87%.
3,5-Dihydro-3,6-diphenyl-5-(4-methylphenyl)-1,2,3-triazolo[4,5-
d]-1,2,4-triazolo[1,5-a]pyrimidin-◦9-one (12e). White crystals
(314 mg, 75% yield), mp: >300 C; IR (KBr) cm−1 1732 (C O),
=
1543, 1510; 1H NMR (400 MHz, CDCl3) d 2.48 (s, 3H), 7.26–8.09
(m, 14H); 13C NMR (CDCl3, 100 MHz) d 21.1, 121.8, 123.2,
124.8, 127.0 (2), 128.8 (2), 128.9 (2), 129.0 (2), 129.3, 129.5 (2),
130.9 (2), 132.3, 134.9, 141.4, 148.5, 150.2, 150.5, 153.3; MS m/z
(%) 419 (M+, 90), 391 (61), 262 (24), 259 (80), 91 (100); Anal.
Calcd for C24H17N7O: C, 68.73; H, 4.09; N, 23.38. Found: C,
68.80; H, 4.16; N, 22.36%.
3,5-Dihydro-6-methyl-5-(4-methylphenyl)-3-phenyl-1,2,3-triazolo-
[4,5-d]-1,2,4-triazolo[1,5-a]pyrim◦idin-9-one (12f). White crystals
(304 mg, 85% yield), mp: >300 C; IR (KBr) cm−1 1737 (C O),
1558, 1517; H NMR (400 MHz, CDCl3) d 2.48 (s, 3H), 2.51 (s,
=
1
12 S.-I. Nagai, S. Takemoto, T. Ueda, K. Mizutani, Y. Uozumi and H.
Tokuda, J. Heterocycl. Chem., 2001, 38, 1097.
13 E. Palaska, G. Sahin, P. Kelicen, N. T. Durlu and G. Altinok, Farmaco,
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14 M. W. Ding, S. Z. Xu and J. F. Zhao, J. Org. Chem., 2004, 69, 8366.
15 M. W. Ding, S. J. Yang and J. Zhu, Synthesis, 2004, 75.
16 Y. Liang, M. W. Ding, Z. J. Liu and X. P. Liu, Synth. Commun., 2003,
33, 2843.
3H), 7.34–8.05 (m, 9H); 13C NMR (CDCl3, 100 MHz) d 11.9,
21.2, 122.2 (2), 124.7, 126.7 (2), 127.6, 129.5 (2), 129.6, 131.1 (2),
134.7, 141.9, 148.5, 149.7, 150.2, 153.6; MS m/z (%) 357 (M+, 70),
329 (49), 288 (21), 259 (26), 91 (100). Anal. Calcd for C19H15N7O:
C, 63.86; H, 4.23; N, 27.44. Found: C, 63.73; H, 4.36; N, 27.31%.
17 M. W. Ding, Y. Sun, S. J. Yang, X. P. Liu and Z. J. Liu, Synth. Commun.,
2003, 33, 1651.
18 M. W. Ding, Y. Sun, X. P. Liu and Z. J. Liu, Org. Prep. Proced. Int.,
2003, 35, 391.
Acknowledgements
19 H. Wamhoff and G. Haffmanns, Chem. Ber., 1984, 117, 585.
20 M. W. Ding, Y. F. Chen and N. Y. Huang, Eur. J. Org. Chem., 2004,
3872.
We gratefully acknowledge financial support of this work by the
National Basic Research Program of China (2004CCA00100) and
the National Natural Science Foundation of China (Project No.
20102001).
21 J. F. Zhao, C. Xie, M. W. Ding and H. W. He, Chem. Lett., 2005, 34,
1022.
1 3 4 | Org. Biomol. Chem., 2006, 4, 130–134
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The Royal Society of Chemistry 2006
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