A novel and efficient one-pot synthesis of 2-aminopyrimidinones and their self-assembly

Article abstract of DOI:10.1002/hlca.200900319

A three-component reaction of benzaldehyde derivatives, methyl cyanoacetate, and guanidinium carbonate affords 2-amino-4-aryl-1,6-dihydro-6- oxopyrimidine-5-carbonitriles and the four-component reaction of benzaldehyde derivatives, methyl cyanoacetate, and guanidinium hydrochloride in the presence of piperidine leads to piperidinium salts of pyrimidinones. X-ray crystallography data confirm self-assembly and H-bonding in these compounds.

Full text of DOI:10.1002/hlca.200900319

Helvetica Chimica Acta – Vol. 93 (2010)
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A Novel and Efficient One-Pot Synthesis of 2-Aminopyrimidinones and Their
Self-Assembly
by Morteza Bararjaniana), Saeed Balalaie*a), Frank Romingerb), and Sanaz Baroutia)
a) Peptide Chemistry Research Group, K. N. Toosi University of Technology,
P.O. Box 15875-4416 Tehran, Iran (fax: þ 98-21-22853650; e-mail: balalaie@kntu.ac.ir)
b) Organisch-Chemisches Institut der Universitꢀt Heidelberg, Im Neuenheimer Feld 270,
D-69120 Heidelberg
Dedicated to Prof. Abdoljalil Mostashari on the occasion of his 70th birthday
A three-component reaction of benzaldehyde derivatives, methyl cyanoacetate, and guanidinium
carbonate affords 2-amino-4-aryl-1,6-dihydro-6-oxopyrimidine-5-carbonitriles and the four-component
reaction of benzaldehyde derivatives, methyl cyanoacetate, and guanidinium hydrochloride in the
presence of piperidine leads to piperidinium salts of pyrimidinones. X-ray crystallography data confirm
self-assembly and H-bonding in these compounds.
Introduction. – The H-bond is one of the most important interactions for molecular
recognition in supramolecular chemistry [1]. Designed supramolecular interactions
continue to play a central role in the development of novel and functional nanoscale
devices and materials. In this way, syntheses of molecules capable of forming defined
H-bonding interactions have led to the creation of artificial self-assembling structures.
Recently, studies on supramolecular noncovalent polymers which have potential
applications in nanotechnology, crystal engineering, and particularly in organic media
containing H-bonding are in progress [2]. In these molecules, H-bonding is
considerably strong, and in the solid phase, X-ray diffraction provides visualization
of H-bonded arrays. The synthesis and characterization of novel structures which are
able to form additional H-bonds is of great importance [3][4].
2-Aminopyrimidinones have received significant attention, because of their diverse
biological activities [5], such as inhibitors of GSK3b (glycogen synthase kinase 3b) [6].
Furthermore, compound A and its derivatives are inhibitors of HSP90 activity in vitro
or in vivo, and are used, inter alia, in the treatment of cancer. The starting materials for
the synthesis of derivatives of compound A are 2-amino-4-aryl-1,6-dihydro-6-oxopyr-
imidine-5-carbonitriles B [7].
ꢁ 2010 Verlag Helvetica Chimica Acta AG, Zꢂrich

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There are several reports on syntheses of 2-aminopyrimidinones, for example, a) by
condensation reactions of 1,3-dicarbonyl compounds such as b-aldehyde esters, b-keto
esters, and b-diesters with guanidinium hydrochloride [8], b) by condensation of
arylmethylidene malononitriles with amidines and guanidinium carbonate [9], c) by
reaction of cyanoacetamide and N-cyanoimidates [10], or d) by three-component
condensation of aromatic aldehydes, methyl cyanoacetate, and guanidinium carbonate
in the presence of a strong base [7].
However, the syntheses of these compounds usually require lengthy routes with low
yields and suffer from drawbacks such as laborious synthesis of starting materials, long
reaction times, or use of highly basic catalysts.
Thus, the development of a method to synthesize 2-aminopyrimidinones in one step
would be desirable. Herein, we report simple and efficient one-pot, three-, and four-
component reactions for the synthesis of 2-aminopyrimidones (Schemes 1 and 2).
Scheme 1
Scheme 2
The one-pot three-component reaction of benzaldehyde derivatives 1, methyl
cyanoacetate (2), and guanidinium carbonate (3) gave 2-amino-4-aryl-1,6-dihydro-6-
oxopyrimidine-5-carbonitriles (4) (Scheme 1).
The advantage of this synthetic method is that strongly basic conditions are not
required in comparison with the reported method [7]. The results of the synthesis of
2-amino-4-aryl-1,6-dihydro-6-oxopyrimidine-5-carbonitriles (4) are summarized in
Table 1.
The products were characterized on the basis of their NMR spectra and mass
1
spectrometric data. For example, the H-NMR spectrum of 4e exhibited a signal at
11.90 ppm due to the lactam NH group. The H-decoupled 13C-NMR spectrum of 4e
revealed two distinct resonances at 116.8 and 118.3 ppm for the two CN groups, whilst
the signal of the CO group appeared at 170.0 ppm.

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Table 1. Synthesis of 2-Amino-4-aryl-1,6-dihydro-6-oxopyrimidine-5-carbonitriles 4
Product
Ar
Yield [%]a)
4a
4b
4c
4d
4e
4f
4g
4h
4i
C6H5
41
52
48
36
40
42
39
62
43
54
4-BrꢀC6H4
4-ClꢀC6H4
2,3-Cl2ꢀC6H3
4-NCꢀC6H4
4-MeꢀC6H4
3-HOꢀC6H4
4-HOꢀC6H4
3-O2NꢀC6H4
4-O2NꢀC6H4
4j
a) Yields of isolated pyrimidinone.
We also attempted a one-pot, four-component condensation reaction of aromatic
benzaldehydes (1), methyl cyanoacetate (2), guanidinium hydrochloride (5), and
piperidine (6), in which the latter acts both as a base and reagent (Scheme 2). The
results are summarized in Table 2. A 1H-NMR experiment was performed in
(D6)DMSO, as a solvent which is known to disrupt H-bonds. However, in our
experiment, the 1H-NMR data indicated the formation of zwitterionic product
structures 7a – 7e. The integral of the H-signals of the piperidinium ions in relation to
the aromatic H-signals amounts to 1:2. The outcome of X-ray structural determi-
nations on 7b and 7c confirms these results. According to the X-ray structure data, it is
confirmed that the two pyrimidinonate skeletons contain one negative charge. The
molecular structure of compound 7b is shown in Fig. 1, which demonstrates the
formation of the zwitterionic product and the essential role of piperidinium ions in the
construction of the salt. Piperidinium pyrimidinonate 7c was crystallized and
characterized by X-ray diffraction as well. The structure is almost isomorphous with
the structure of 7b and thus verifies the formation of an analogous supramolecular
structure. Therefore, only the structure of 7b will be discussed in detail.
Table 2. Synthesis of Piperidinium Pyrimidinonate 7 via One-Pot Four-Component Reaction
Product
Ar
Yield [%]a)
7a
7b
7c
7d
7e
C6H5
48
62
59
53
43
4-BrꢀC6H4
4-ClꢀC6H4
4-MeꢀC6H4
4-F3CꢀC6H4
a) Yields of isolated 7.
The X-ray structure clearly shows three H-bonds (N13 ··· O35: 2.91 ꢃ, N14 ··· N34:
2.86 ꢃ, N33 ··· O15: 2.82 ꢃ) connecting a pair of molecules (Fig. 1). The role of the
piperidinium ion in the molecular association is crucial. Two of them act as tethers to

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Fig. 1. Thermal ellipsoid plot of the triple H-bridged motif observed for compound 7b. The dashed lines
with open ends indicate other H-bridges to neighboring molecules as described in the text.
connect via H-bridges two pairs of molecules piled upon each other. These H-bridges
are N1 ··· O35 with 2.87 ꢃ and N1 ··· O15’ with 2.82 ꢃ (see Figs. 1 and 2).
Fig. 2. In the crystal structure of compound 7b, the H-bonding and the tetrameric unit is recognizable
As can be concluded from the structures, piperidine mediates the association by
making three complementary H-bonds possible. The formation of the piperidinium salt

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781
generates the AAD face and provides a DDA-AAD pairing interaction. The piled
molecular pairs show p – p interactions between the stacked heterocycles. The distances
of the overlapping atoms to the opposite ring planes amount to only 3.375 ꢃ (C35’),
3.455 ꢃ (C36’), 3.392 ꢃ (N12’), and 3.319 ꢃ (C13’).
In addition to X-ray crystallography data, other techniques were used for the
1
confirmation of the molecular association, such as H-NMR spectroscopy and high-
resolution mass spectrometry. The ratio of the signals for the H-atoms of the piperidine
ring and also of the aromatic H-atoms in the 1H-NMR spectra was used for determining
the piperidinium/pyrimidinonate ratio. HR-MS data for compound 7a confirmed
molecular association with an m/z value of 510.2326 (C27H28N9O2) and showed the ratio
piperidinium/pyrimidinonate to be 1:2.
In summary, we have described efficient one-pot three- and four-component
reactions for the synthesis of 2-amino-4-aryl-1,6-dihydro-6-oxopyrimidine-5-carbo-
nitriles and their piperidinium salts. X-Ray crystallography data of the piperidinium
salts of 7b and 7c confirmed self-assembly of these compounds via H-bonding. The use
of the simple and available starting materials, the high bond forming efficiency, and the
atom economy are advantages of this method.
Saeed Balalaie is grateful to INSF (Iran National Science Foundation) for financial support. We are
also thankful to the K. N. Toosi University of Technology research council for partial financial support.
Experimental Part
General. All commercially available materials were used without further purification. All reactions
were followed by TLC (silica gel 60 F254; Merck). The detection was performed with UV light. Column
chromatography (CC): silica gel 60 (200 – 300 mesh; Merck). M.p.: Electrothermal 9100 apparatus;
uncorrected. IR Spectra: ABB FT-IR (FTLA 2000) spectrometer; n˜ in cmꢀ1. 1H- and 13C-NMR: Bruker
DRX-300 Avance in (D6)DMSO at 300 and 75 MHz, resp.; d in ppm rel. to Me4Si as internal standard,
J in Hz. HR-MS: Jeol JMS-700 (HR-EI), (HR-FAB) and ESI-POS (Bruker Apex Qe-FT-ICR
instrument) spectrometer; in m/z (rel. %).
General Procedure for the Synthesis of 2-Amino-4-aryl-1,6-dihydro-6-oxopyrimidine-5-carbonitriles
4a – 4j. A soln. of aromatic aldehyde 1 (2 mmol), 2 (2.1 mmol, 0.20 g), and 3 (1.1 mmol, 0.20 g) in MeOH
(25 ml) was heated at reflux. The progress of the reaction was monitored by TLC (hexane/AcOEt 3 :1).
On completion, HCl (2m) was added to neutralize the mixture. The precipitated solid was filtered,
washed with cold CH2Cl2 and H2O. The products were obtained in yields of 36 – 62%.
2-Amino-1,6-dihydro-6-oxo-4-phenylpyrimidine-5-carbonitrile (4a). Yield: 87 mg (41%). M.p. 344 –
3468 (dec.). IR (KBr): 3392, 3138, 2223, 1638. 1H-NMR (300 MHz, (D6)DMSO): 7.00 (br. s, NH2); 7.45 –
7.59 (m, 3 arom. H); 7.68 – 7.71 (m, 2 arom. H); 11.79 (br. s, NH). 13C-NMR (75 MHz, (D6)DMSO): 84.8;
117.3; 128.2; 130.9; 136.6; 156.4; 161.7; 171.6. EI-HR-MS: 212.0700 (C11H8N4Oþ; calc. 212.0698).
2-Amino-4-(4-bromophenyl)-1,6-dihydro-6-oxopyrimidine-5-carbonitrile (4b). Yield: 152 mg
(52%). M.p. 284 – 2868 (dec.). IR (KBr): 3392, 3153, 2215, 1669. 1H-NMR (300 MHz, (D6)DMSO):
7.10 (br. s, NH2); 7.70 (br. s, 4 arom. H); 12.00 (br. s, NH). 13C-NMR (75 MHz, (D6)DMSO): 84.3; 117.7;
124.3; 130.3; 131.3; 136.0; 158.0; 164.2; 170.1. EI-HR-MS: 291.9796 (C11H781BrN4Oþ; calc. 291.9783),
289.9810 (C11H779BrN4Oþ; calc. 289.9804).
2-Amino-4-(4-chlorophenyl)-1,6-dihydro-6-oxopyrimidine-5-carbonitrile (4c). Yield: 120 mg (48%).
M.p. 346 – 3488 (dec.). IR (KBr): 3400, 3138, 2215, 1638. 1H-NMR (300 MHz, (D6)DMSO): 7.00 (br. s,
NH2); 7.60 (d, J ¼ 8.0, 2 arom. H); 7.80 (d, J ¼ 8.0, 2 arom. H); 11.80 (br. s, NH). 13C-NMR (75 MHz,
(D6)DMSO): 84.9; 117.1; 128.4; 130.1; 135.3; 135.7; 156.5; 161.7; 170.3. EI-HR-MS: 248.0249
(C11H737ClN4Oþ; calc. 248.0227), 246.0310 (C11H735ClN4Oþ; calc. 246.0308).

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2-Amino-4-(2,3-dichlorophenyl)-1,6-dihydro-6-oxopyrimidine-5-carbonitrile (4d). Yield: 101 mg
(36%). M.p. 322 – 3238 (dec.). IR (KBr): 3330, 3123, 2223, 1648. 1H-NMR (300 MHz, (D6)DMSO):
7.10 (br. s, NH); 7.46 – 7.51 (m, 2 arom. H); 7.79 – 7.81 (m, 1 arom. H); 8.40 (br. s, NH); 11.90 (br. s, NH).
13C-NMR (75 MHz, (D6)DMSO): 87.5; 115.7; 128.2; 128.6; 131.5; 132.1; 138.5; 157.0; 160.6; 170.9. EI-
HR-MS: 283.9860 (C11H637Cl2N4Oþ; calc. 283.9860), 281.9900 (C11H637Cl35ClN4Oþ; calc. 281.9911),
279.9918 (C11H635Cl2N4Oþ; calc. 279.9919).
2-Amino-4-(4-cyanophenyl)-1,6-dihydro-6-oxopyrimidine-5-carbonitrile (4e). Yield: 95 mg (40%).
M.p. 360 – 3618 (dec.). IR (KBr): 3392, 3146, 2215, 1654. 1H-NMR (300 MHz, (D6)DMSO): 7.10 (br. s,
NH); 7.90 (d, J ¼ 8.3, 2 arom. H); 8.00 (d, J ¼ 8.3, 2 arom. H); 8.40 (br. s, NH); 11.90 (br. s, NH).
13C-NMR (75 MHz, (D6)DMSO): 85.5; 113.2; 116.8; 118.3; 129.1; 132.3; 140.9; 156.7; 161.5; 170.0. EI-
HR-MS: 237.0625 (C12H7N5Oþ; calc. 237.0650).
2-Amino-1,6-dihydro-4-(4-methylphenyl)-6-oxopyrimidine-5-carbonitrile (4f). Yield: 95 mg (42%).
M.p. 329 – 3308 (dec.). IR (KBr): 3330, 3100, 2230, 1670. 1H-NMR (300 MHz, (D6)DMSO): 2.40 (s, Me);
7.10 (br. s, NH); 7.30 (d, J ¼ 8.6, 2 arom. H); 7.70 (d, J ¼ 8.6, 2 arom. H); 8.30 (br. s, NH); 11.90 (br. s,
NH). 13C-NMR (75 MHz, (D6)DMSO): 21.0; 85.0; 117.4; 128.3; 128.8; 133.7; 140.0; 156.4; 161.7; 170.5.
EI-HR-MS: 226.0840 (C12H10N4Oþ; calc. 226.0854).
2-Amino-1,6-dihydro-4-(3-hydroxyphenyl)-6-oxopyrimidine-5-carbonitrile (4g). Yield: 90 mg
(39%). M.p. 330 – 3328 (dec.). IR (KBr): 3407, 3138, 2215, 1661. H-NMR (300 MHz, (D6)DMSO):
6.80 (br. s, NH); 6.90 (d, J ¼ 7.5, 1 arom. H); 7.18 – 7.29 (m, 2 arom. H); 7.30 (t, J ¼ 7.5, 1 arom. H); 8.20
(br. s, NH); 9.80 (br. s, OH); 11.70 (br. s, NH). 13C-NMR (75 MHz, (D6)DMSO): 84.7; 115.0; 117.2;
117.9; 119.0; 129.3; 137.8; 156.4; 157.1; 161.8; 71.7. EI-HR-MS: 228.0649 (C11H8N4Oþ2 ; calc. 228.0648).
2-Amino-1,6-dihydro-4-(4-hydroxyphenyl)-6-oxopyrimidine-5-carbonitrile (4h). Yield: 141 mg
(62%). M.p. 320 – 3228 (dec.). IR (KBr): 3369, 3100, 2223, 1676. 1H-NMR (300 MHz, (D6)DMSO):
6.80 (br. s, NH2); 6.90 (d, J ¼ 8.5, 2 arom. H); 7.80 (d, J ¼ 8.5, 2 arom. H); 10.20 (br. s, OH); 11.60 (br. s,
NH). 13C-NMR (75 MHz, (D6)DMSO): 83.3; 117.8; 127.0; 129.0; 130.4; 156.1; 160.3; 162.1; 170.7. EI-HR-
MS: 228.0649 (C11H8N4Oþ2 ; calc. 228.0648).
2-Amino-1,6-dihydro-4-(3-nitrophenyl)-6-oxopyrimidine-5-carbonitrile (4i). Yield: 103 mg (43%).
M.p. 310 – 3128 (dec.). IR (KBr): 3400, 3153, 2215, 1653. 1H-NMR (300 MHz, (D6)DMSO): 7.10 (br. s,
NH2); 7.80 (t, J ¼ 8.2, 1 arom. H); 8.20 (d, J ¼ 8.2, 1 arom. H); 8.40 (d, J ¼ 8.2, 1 arom. H); 8.60 (br. s, 1
arom. H); 11.80 (br. s, NH). 13C-NMR (75 MHz, (D6)DMSO): 85.3; 116.8; 123.0; 125.5; 130.1; 134.5;
137.9; 147.6; 156.7; 161.5; 168.9. EI-HR-MS: 257.0569 (C11H7N5Oþ3 ; calc. 257.0549).
2-Amino-1,6-dihydro-4-(4-nitrophenyl)-6-oxopyrimidine-5-carbonitrile (4j). Yield: 139 mg (54%).
M.p. 320 – 3238 (dec.). IR (KBr): 3392, 3138, 2215, 1661, 1530, 1361. 1H-NMR (300 MHz, (D6)DMSO):
7.10 (br. s, NH); 8.00 (d, J ¼ 10.5, 2 arom. H); 8.30 (d, J ¼ 10.5, 2 arom. H); 11.90 (br. s, NH). 13C-NMR
(75 MHz, (D6)DMSO): 85.7; 116.7; 123.5; 129.7; 142.6; 148.7; 156.7; 161.4; 169.7. EI-MS (70 eV): 257.1
(100, Mþ), 215 (50), 169 (20), 141 (17).
General Procedure for the Synthesis of Piperidinium 2-Amino-6-aryl-5-cyano-4-oxo-4H-pyrimidin-3-
ide – 2-Amino-4-aryl-1,6-dihydro-6-oxopyrimidine-5-carbonitriles 7a – 7e. A soln. of aromatic aldehyde 1
(2 mmol), 2 (2.1 mmol, 0.20 g), 5 (2.2 mmol, 0.20 g), and 6 (0.34 g, 4 mmol) in MeOH (50 ml) was heated
at reflux. The progress of the reaction was monitored by TLC (hexane/AcOEt 3 :1). The solvent was
removed under reduced pressure, and MeCN was added to the mixture. The precipitated solid was
filtered and further purified by crystallization from EtOH. The yields of the products were 43 – 62%.
Piperidinium 2-Amino-5-cyano-4-oxo-6-phenyl-4H-pyrimidin-3-ide – 2-Amino-1,6-dihydro-6-oxo-4-
phenylpyrimidine-5-carbonitrile (1:1) (7a). Yield: 244 mg (48%). M.p. 290 – 2928 (dec.). IR (KBr): 3430,
1
3323, 2946, 2208, 1676, 1523. H-NMR (300 MHz, (D6)DMSO): 1.50 – 1.77 (m, 3 CH2); 2.90 – 3.00 (m,
2 CH2N); 4.00 (br. s, 7 NH); 7.40 – 7.62 (m, 6 arom. H); 7.75 – 7.90 (m, 4 arom. H). 13C-NMR (75 MHz,
(D6)DMSO): 21.8; 22.5; 43.9; 83.5; 118.8; 128.0; 128.1; 130.2; 137.4; 160.4; 168.4; 170.7. FAB-HR-MS
(pos.): 510.2326 ([M þ 1]þ, C27H28N9O2þ ; calc. 510.2366), 298.1669 (C16H20N5Oþ; calc. 298.1668),
213.0780 (C11H9N4Oþ; calc. 213.0776).
Piperidinium 2-Amino-6-(4-bromophenyl)-5-cyano-4-oxo-4H-pyrimidin-3-ide – 2-Amino-4-(4-bromo-
phenyl)-1,6-dihydro-6-oxopyrimidine-5-carbonitrile (1:1) (7b). Yield: 368 mg (62%). M.p. 250 – 2528
(dec.). IR (KBr): 3407, 3350, 3207, 2948, 2207, 1676, 1523. 1H-NMR (300 MHz, (D6)DMSO): 1.50 – 1.75
(m, 3 CH2); 2.95 – 3.10 (m, 2 CH2N); 3.60 (br. s, 7 NH); 7.70 (dd, J ¼ 8.0, 8 arom. H). 13C-NMR (75 MHz,

Helvetica Chimica Acta – Vol. 93 (2010)
783
(D6)DMSO): 21.8; 22.4; 43.8; 83.4; 118.7; 123.8; 130.3; 131.2; 136.6; 160.6; 168.6; 169.4. ESI-MS: 378.3
([M ꢀ C11H8781BrN4O þ 1]þ), 376.3 ([M ꢀ C11H779BrN4O þ 1]þ), 293.2 (C11H881BrN4Oþ), 291.2
(C11H879BrN4Oþ).
Piperidinium 2-Amino-6-(4-chlorophenyl)-5-cyano-4-oxo-4H-pyrimidin-3-ide – 2-Amino-4-(4-chloro-
phenyl)-1,6-dihydro-6-oxopyrimidine-5-carbonitrile (1:1) (7c). Yield: 343 mg (59%). M.p. 294 – 2958
(dec.). IR (KBr): 3400, 3100, 2207, 1661, 1530. 1H-NMR (300 MHz, (D6)DMSO): 1.50 – 1.70 (m, 3 CH2);
3.00 (t, J ¼ 5.5, 2 CH2N); 4.00 (br. s, 7 NH); 7.55 (d, J ¼ 8.5, 4 arom. H); 7.80 (d, J ¼ 8.5, 4 arom. H).
13C-NMR (75 MHz, (D6)DMSO): 21.8; 22.4; 43.9; 83.5; 118.6; 128.2; 130.0; 135.0; 136.2; 160.5; 168.4;
169.3. FAB-HR-MS (pos.): 334.1282 ([M ꢀ C11H737ClN4O þ 1]þ, C16H1937ClN5Oþ; calc. 334.1248),
Table 3. Crystallographic Data for Compounds 7b and 7c
7b
7c
Chemical formula
Mr
C27H25Br2N9O2
667.38
C27H25Cl2N9O2
578.46
Crystal system
Space group
Triclinic
P1
Triclinic
P1
ꢀ
ꢀ
a [ꢃ]
b [ꢃ]
c [ꢃ]
a [8]
b [8]
g [8]
V [ꢃ3]
9.447(3)
10.888(4)
15.047(5)
103.24(1)
102.66(1)
92.45(1)
1462.8(9)
2
9.322(1)
10.932(2)
14.682(2)
102.16(1)
102.42(1)
92.61(1)
1421.9(4)
2
Z
Calc. density Dx [Mg mꢀ3
Radiation type
Wavelength (l)
qrange [8]
]
1.515
MoKa
0.71073
1.4 – 27.5
2.81
1.35
MoKa
0.71073
1.9 – 27.5
0.271
m [mmꢀ1
]
Temperature [K]
Crystal shape
Crystal size [mm3]
Crystal color
200(2)
200(2)
polyhedron
0.22 ꢁ 0.18 ꢁ 0.10
yellow
polyhedron
0.24 ꢁ 0.22 ꢁ 0.2
yellow
Diffractometer
Data collection method
No. of measured reflexions
Bruker Smart CCD
0.38 w-scans
15282
Bruker Smart CCD
0.38 w-scans
14901
No. of independent reflexions
6670
6469
No. of observed reflexions
4890
4547
Criterion of observed reflexions
Rint
I > 2s(I)
0.0266
I > 2s(I)
0.0299
qmax [8]
27
27
R
0.037
0.042
wR
0.089
0.112
No. of parameters
hmin/hmax
kmin/kmax
407
407
ꢀ 12/12
ꢀ 14/14
ꢀ 19/19
1.01
0.61
ꢀ 0.51
ꢀ 12/12
ꢀ 14/14
ꢀ 19/18
1.04
0.43
ꢀ 0.32
lmin/lmax
Goodness-of-fit on F2
D1max
D1min

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332.1300 ([M ꢀ C11H735ClN4O]þ, C16H1935ClN5Oþ; calc. 332.1278), 249.0374 (C11H837ClN4Oþ; calc.
249.0359), 247.0413 (C11H835ClN4Oþ; calc. 247.0387).
Piperidinium 2-Amino-6-(4-methylphenyl)-5-cyano-4-oxo-4H-pyrimidin-3-ide – 2-Amino-1,6-dihy-
dro-4-(4-methylphenyl)-6-oxopyrimidine-5-carbonitrile (1:1) (7d). Yield: 286 mg (53%). M.p. 280 – 2818
(dec.). IR (KBr): 3500, 3400, 3332, 2200, 1669. 1H-NMR (300 MHz, (D6)DMSO): 1.40 – 1.65 (m, 3 CH2);
2.35 (s, 2 Me); 2.80 (t, J ¼ 5.5, 2 CH2N); 4.2 (br. s, 7 NH2); 7.35 (d, J ¼ 8.0, 4 arom. H); 7.70 (d, J ¼ 8.0, 4
arom. H). 13C-NMR (75 MHz, (D6)DMSO): 21.0; 21.9; 22.5; 43.8; 83.2; 119.0; 128.2; 128.6; 134.6; 140.1;
160.4; 168.6; 170.5. ESI-MS: 312.3 ([M ꢀ C12H10N4O þ 1]þ), 227.3 (C12H11N4Oþ).
Piperidinium 2-Amino-5-cyano-4-oxo-6-[4-(trifluoromethyl)phenyl]-4H-pyrimidin-3-ide-2-Amino-
1,6-dihydro-6-oxo-4-[4-(trifluoromethyl)phenyl]pyrimidine-5-carbonitrile (1 :1) (7e). Yield: 278 mg
1
(43%). M.p. > 3108 (dec.). IR (KBr): 3476, 3315, 3192, 2207, 1684. H-NMR (300 MHz, (D6)DMSO):
1.55 – 1.70 (m, 3 CH2); 2.99 (t, J ¼ 5.5, 2 CH2N); 4.4 (br. s, 7 NH); 7.85 (d, J ¼ 8.2, 4 arom. H); 7.96 (d, J ¼
8.2, 4 arom. H). 13C-NMR (75 MHz, (D6)DMSO): 21.8; 22.4; 43.8; 84.0; 118.5; 122.3; 125.1; 125.2; 125.3;
125.9; 129.1; 130.1; 130.5; 141.4; 160.8; 168.5; 169.4. ESI-MS: 366.3 ([M ꢀ C12H7F3N4O]þ), 281.4
(C12H8F3N4Oþ).
X-Ray Structure Determination of Compounds 7b and 7c. The crystallographic data are presented in
Table 3. Intensities were corrected for Lorentz and polarization effects, an empirical absorption
correction was applied using SADABS [11] based on the Laue symmetry of the reciprocal space, m ¼
0.27 mmꢀ1, structure solved by direct methods and refined against F2 with a full-matrix least-squares
algorithm using the SHELXTL-PLUS (5.10) software package [12]. H-atoms were treated using
appropriate riding models except for the H-atoms bonded to N-atoms, which were refined isotropically,
goodness-of-fit ¼ 1.01 for 7b and 1.04 for 7c. Further details of crystal structures of compounds 7b and 7c
can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge CB21EZ, UK (e-
mail: deposit@ccdc.cm.ac.uk), quoting the deposition numbers CCDC-734321 and -734322, resp.
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Received September 3, 2009