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Chemistry of Heterocyclic Compounds

, Volume 48, Issue 4, pp 613–619 | Cite as

One-pot synthesis of 4-aryl-2-cyanoimino-3,4-dihydro-1H-pyrimidines and their reactions

  • A. H. Moustafa
  • A. S. Shestakov
  • Kh. S. Shikhaliev
Article

A series of 4-aryl-2-cyanoimino-3,4-dihydro-1H-pyrimidines was obtained as a result of a multicomponent Biginelli reaction using 1,3-dicarbonyl compounds, aromatic aldehydes, and cyanamide. Alkylation of the obtained compounds with benzyl chloride takes place at the two nitrogen atoms of the tetrahydropyrimidine ring, while oxidation with manganese dioxide leads to the corresponding 1-(pyrimidin-2-yl)carbamides or pyrimidine-2-amines, depending on the conditions.

Keywords

cyanamide N-cyanoimine dihydropyrimidine alkylation Biginelli reaction oxidation 

N-Cyanoimines are similar in structure to cyanamides. The difference is in the presence of the C = N bond, which appreciably increases the basicity of the nitrile group nitrogen atom [1] and extends the possibilities of using these compounds as synthons [2]. Antimycotic [3] and hypoglycaemic [4,5] activity has been detected in certain cyanoiminopyrimidines.

The synthesis of N-cyanoimines is most often based on the use of bis-electrophiles containing the structural fragment C = N–C ≡ N: dimethyl cyanoimidodithiocarbonate [4, 5, 6, 7, 8] or diphenyl cyanoimidocarbonate [9]. Cyanoguanidine leads to the required cyanoiminodihydropyrimidines upon condensation with acrylic acid derivatives [10] or upon successive interaction with aldehydes and 1,3-dicarbonyl compounds [11,12]. In the last case the methodology of the Biginelli reaction was employed; this proved productive also in the case where two equivalents of the cyanamide serve as the nitrogen-containing component [13]. The aim of the present study was investigation of the three-component reaction of the formation of 3,4-dihydro-1H-pyrimidines and their derivatives.

The reaction of aromatic aldehydes with 1,3-dicarbonyl compounds and cyanamide takes place upon refluxing in a water–alcohol mixture in the presence of sodium acetate and hydrochloric acid. These conditions are optimal [13] for production of the target cyanoiminodihydropyrimidines 1.

At the present time the following order of the reagents' mixing is generally accepted for the Biginelli reaction: aldehyde + amino component + ethyl acetoacetate [14]. This makes it possible to suppose that nucleophilic addition of the cyanamide to the aldehyde occurs at the first stage. Under the conditions of acid catalysis the intermediate A is formed, and this quickly adds a second molecule of cyanamide. Such a direction of reaction is promoted by the weakly acidic medium (pH ~5) created by acetate buffer. The intermediate B, thus formed carrying a positive charge, adds a molecule of ethyl acetoacetate with formation of the intermediate compound C. The aldehyde carbon atom acts as the electrophilic center. This is confirmed by the effect of the substituent nature on the reaction yield: the appearance of electron-donating methoxy and ethoxy substituents at position 4 of the aromatic ring reduces the yield, whereas a nitro group at position 2 increases it. The mechanism as a whole corresponds to that proposed earlier for the formation of 4-aryl-2-cyanoimino-6-methyl-3,4-dihydro-1H-pyrimidines [13].

With acetylacetone the reaction is not so straightforward. The respective dihydropyrimidines could only be obtained with 4-NO2- and 4-Cl-benzaldehydes. It is known that cyanamide with 1,3-diketones in aqueous media gives the corresponding 2-aminopyrimidines along with the linear addition products [15]. In this case, another side reaction apparently occurs. Acetylacetone reacts less vigorously with compound B, and the cyanamide begins to compete with it, leading to formation of the intermediate D, which undergoes cyclization to compound E. Thus, when 4-MeO- and 4-EtO-benzaldehydes were used a mixture of products was obtained where according to spectral data the compound containing the aromatic ring and the fragment with five magnetically inequivalent protons predominated. This suggestion is also supported by the fact that compound 2, the formation of which likewise does not involve the 1,3-dicarbonyl component, was isolated earlier in the absence of ethanol from the reaction mixture [13].

The dihydropyrimidines 1 can exist in various tautomeric forms. The data from quantum-chemical calculations, performed for compound 1e, give preference for tautomer F. Its energy is 43.16 kJ/mol lower than the energy of tautomer G and 75.82 kJ/mol lower than that of tautomer H. The results of the calculations are confirmed by the data from NOESY spectroscopy. In the spectrum of compound 1e there is a correlation peak at 5.27/9.15 ppm, corresponding to the interaction of the protons at positions 4 and 3 of the dihydropyrimidine ring, and there are correlation peaks at 5.27/7.26 and 7.26/9.15 ppm, which correspond to the interaction of these protons with the ortho-protons of the aromatic ring. In addition, the spectrum contains a correlation peak at 2.32/10.21 ppm, corresponding to interaction of the methyl group protons with the proton at position 1 of the pyrimidine system. Analogous correlation peaks are observed in the NOESY spectrum of compound 1i.

The presence of sufficiently mobile protons at positions 1 and 3 of the dihydropyrimidines 1 makes it possible to use these compounds in alkylation reactions. According to data from quantum-chemical calculations, the separation energy of the NH proton at positions 1 and 3 amounts to 1424.67 and 1451.94 kJ/mol. respectively, which indicates almost identical probability that both nitrogen atoms participate in the alkylation. In fact, attempts to obtain the monoalkyl derivatives of the dihydropyrimidines 1b,e by treatment of their sodium salts with an equimolar amount of benzyl chloride led, according to data from TLC, to a mixture of products. With a threefold excess of benzyl chloride under the same conditions it was possible to obtain the dialkyl derivatives 3a,b.
Oxidation of the dihydropyrimidines 1b,e leads to the pyrimidines 4a,b or 5a,b, depending on the conditions [12]. Under mild conditions with refluxing in acetone, the 2-carbamoylaminopyrimidines 4a,b are formed. Refluxing in xylene leads to the 2-aminopyrimidines 5a,b.

The oxidation processes are easily followed by means of the IR spectra of compounds 1, 4, and 5. Thus, after mild oxidation the absorption bands at 2175 and 1633 cm−1 corresponding to the nitrile group and the C = N bond between the carbon at position 2 of the dihydropyrimidine ring and the exocyclic nitrogen atom, disappear in the spectra of the starting dihydropyrimidines. In the spectrum of the obtained compound 4a, an absorption band corresponding to vibrations of the amide fragment appears at 1694 cm−1. In the 1 H NMR spectrum of compound 4a, the protons of the NH2 group are reflected in two broad signals at 6.89 and 8.43 ppm, that is apparently due to the formation of an intramolecular hydrogen bond. A similar pattern is observed in the spectrum of compound 4b. After oxidation in xylene, the absorption bands corresponding to the nitrile and amide groups are not observed.

Thus, on the basis of the β-ketoesters(diketones), aromatic aldehydes, and cyanamide it is possible to obtain a wide range of cyanoiminopyrimidines containing a series of reaction centers.

Experimental

The IR spectra were recorded on a Bruker Vertex 70 spectrometer. The 1 H NMR spectra were recorded on a Bruker AC-300 spectrometer (300 MHz) at 27 °C in DMSO-d6 with TMS as internal standard. The NOESY spectra (τmix = 0.6 s) were obtained on a Bruker DRX-500 instrument (500 MHz) at 30 °C in DMSO-d6. The purity of the synthesized compounds and the course of the reactions were monitored by TLC on Merck UV-254 plates (eluent CHCl3–MeOH, 20:1). The quantum-chemical calculations were performed with GAUSSIAN 03 software by the density functional method (B3LYP). Full optimization of the molecular geometry was realized in the 3-21 G* basis set. The electronic structure was calculated in the 6-31 G* basis set.

4-Aryl-2-cyanoimino-6-methyl-3,4-dihydro-1H -pyrimidines 1a-n (General Method). Aldehyde (20 mmol), 1,3-dicarbonyl compound (20 mmol), NaOAc (20 mmol), cyanamide (40 mmol) as 50 % aqueous solution, and conc. HCl (0.4 ml) were added to EtOH (17 ml). The obtained suspension was refluxed for 4 h, and the precipitate formed on cooling was recrystallized from EtOH. The yields and physicochemical properties of compounds 1a-n are given in Table 1, and the spectral data are given in Table 2.
Table 1

Physicochemical Characteristics of Compounds 1a-n

Compound

Empirical formula

\( \frac{{{\text{Found}},\% }}{{{\text{Calculated}},\% }} \)

Mp, °С

Yield, %

C

H

N

1a

C16H18N4O2

\( \frac{{64.37}}{{64.41}} \)

\( \frac{{5.98}}{{6.08}} \)

\( \frac{{18.87}}{{18.78}} \)

298-299

45

1b

C16H18N4O2

\( \frac{{64.52}}{{64.41}} \)

\( \frac{{6.16}}{{6.08}} \)

\( \frac{{18.76}}{{18.78}} \)

246-247

51

1c

C16H18N4O3

\( \frac{{61.12}}{{61.13}} \)

\( \frac{{5.84}}{{5.77}} \)

\( \frac{{17.73}}{{17.82}} \)

235-237

31

1d

C17H20N4O3

\( \frac{{62.07}}{{62.18}} \)

\( \frac{{6.14}}{{6.14}} \)

\( \frac{{17.15}}{{17.06}} \)

222-225

33

1e

C15H15ClN4O2

\( \frac{{56.59}}{{56.52}} \)

\( \frac{{4.63}}{{4.74}} \)

\( \frac{{17.66}}{{17.58}} \)

250-252

42

1f

C15H15FN4O2

\( \frac{{59.56}}{{59.60}} \)

\( \frac{{4.91}}{{5.00}} \)

\( \frac{{18.47}}{{18.53}} \)

267-269

15

1g

C15H15N5O4

\( \frac{{54.67}}{{54.71}} \)

\( \frac{{4.64}}{{4.59}} \)

\( \frac{{21.34}}{{21.27}} \)

205-207 (205-207 [13])

42

1h

C14H13ClN4O

\( \frac{{58.26}}{{58.24}} \)

\( \frac{{4.53}}{{4.54}} \)

\( \frac{{19.48}}{{19.40}} \)

269

26

1i

C14H13N5O3

\( \frac{{56.17}}{{56.18}} \)

\( \frac{{4.41}}{{4.38}} \)

\( \frac{{23.46}}{{23.40}} \)

310-312

67

1j

C19H15ClN4O

\( \frac{{65.10}}{{65.05}} \)

\( \frac{{4.24}}{{4.31}} \)

\( \frac{{15.94}}{{15.97}} \)

235-236

63

1k

C19H15ClN4O

\( \frac{{65.12}}{{65.05}} \)

\( \frac{{4.32}}{{4.31}} \)

\( \frac{{15.81}}{{15.97}} \)

304

38

1l

C14H13ClN4O2

\( \frac{{55.11}}{{55.18}} \)

\( \frac{{4.32}}{{4.30}} \)

\( \frac{{18.47}}{{18.39}} \)

274-275

36

1m

C15H16N4O2

\( \frac{{63.44}}{{63.37}} \)

\( \frac{{5.56}}{{5.67}} \)

\( \frac{{19.71}}{{19.71}} \)

237-238

27

1n

C15H16N4O3

\( \frac{{60.07}}{{59.99}} \)

\( \frac{{5.35}}{{5.37}} \)

\( \frac{{18.73}}{{18.66}} \)

227-228

25

Table 2

Spectral Data of Compounds 1a-n

Compound

IR spectrum, ν, cm–1

1Н NMR, δ, ppm (J, Hz)

1a

3216 (NH), 2209 (С ≡ N), 1727 (С = О), 1663 (C = N)

1.09 (3Н, t, J = 7.1, CH 3CH2); 2.32 (3Н, s, СН3); 2.47 (3Н, s, СН3); 3.97 (2 H, q, J = 7.1, CH 2CH3); 5.51 (1Н, s, Н-4); 7.04-7.22 (4Н, m, Н Ar); 8.79 (1Н, br. s, NH); 9.82 (1Н, br. s, NH)

1b

3318 (NH), 2204 (С ≡ N), 1678 (С = О), 1636 (C = N)

1.16 (3Н, t, J = 7.1, CH 3CH2); 2.30 (3Н, s, СН3); 2.32 (3Н, s, СН3); 4.02 (2 H, q, J = 7.1, CH 2CH3); 5.21 (1Н, s, Н-4); 7.01-7.17 (4Н, m, Н Ar); 8.76 (1Н, br. s, NH); 9.91 (1Н, br. s, NH)

1c

3322 (NH), 2197 (С ≡ N), 1684 (С = О), 1638 (C = N)

1.16 (3Н, t, J = 6.9, CH 3CH2); 2.31 (3Н, s, СН3); 3.76 (3Н, s, OСН3); 4.03 (2 H, q, J = 6.9, CH 2CH3); 5.21 (1Н, s, Н-4); 6.82 (2Н, d, J = 8.1, H-2,6 Ar); 7.17 (2Н, d, J = 8.1, H-3,5 Ar); 8.81 (1Н, br. s, NH); 9.87 (1Н, br. s, NH)

1d

3326 (NH), 2192 (С ≡ N), 1687 (С = О), 1631 (C = N)

1.16 (3Н, t, J = 7.1, CH 3CH2); 1.38 (3Н, t, J = 6.9, CH 3CH2); 2.32 (3Н, s, СН3); 4.01 (4 H, m, 2 CH 2CH3); 5.21 (1Н, s, Н-4); 6.79 (2Н, d, J = 8.5, H-2,6 Ar); 7.15 (2Н, d, J = 8.5, H-3,5 Ar); 8.78 (1Н, br. s, NH); 9.81 (1Н, br. s, NH)

1e

3303 (NH), 2175 (С ≡ N), 1670 (С = О), 1633 (C = N)

1.15 (3Н, t, J = 7.0, CH 3CH2); 2.31 (3Н, s, СН3); 4.04 (2 H, q, J = 7.0, CH 2CH3); 5.28 (1Н, s, Н-4); 7.25 (2Н, d, J = 8.4, H-2,6 Ar); 7.33 (2Н, d, J = 8.4, H-3,5 Ar); 8.92 (1Н, br. s, NH); 9.98 (1Н, br. s, NH)

1f

3312 (NH), 2184 (С ≡ N), 1676 (С = О), 1634 (C = N)

1.16 (3Н, t, J = 6.9, CH 3CH2); 2.31 (3Н, s, СН3); 4.04 (2 H, q, J = 6.9, CH 2CH3); 5.29 (1Н, s, Н-4); 7.01 (2Н, m, H-2,6 Ar); 7.30 (2Н, m, H-3,5 Ar); 8.93 (1Н, br. s, NH); 9.91 (1Н, br. s, NH)

1g

3213 (NH), 2204 (С ≡ N), 1721 (С = О), 1653 (C = N)

0.99 (3Н, t, J = 7.1, CH 3CH2); 2.32 (3Н, s, СН3); 3.91 (2 H, m, 2 CH 2CH3); 6.08 (1Н, s, Н-4); 7.48-7.59 (2Н, m, H Ar); 7.72 (1Н, t, J = 7.8, H Ar); 7.91 (1Н, d, J = 7.8, H Ar); 8.82 (1Н, br. s, NH); 10.11 (1Н, br. s, NH)

1h

3181 (NH), 2196 (С ≡ N), 1687 (С = О), 1653 (C = N)

2.14 (3Н, s, СН3); 2.91 (3Н, s, СН3); 5.38 (1Н, s, Н-4); 7.28-7.37 (4Н, m, H Ar); 9.02 (1Н, br. s, NH); 9.99 (1Н, br. s, NH)

1i

3202 (NH), 2188 (С ≡ N), 1683 (С = О), 1629 (C = N)

2.21 (3Н, s, СН3); 2.39 (3Н, s, СН3); 5.51 (1Н, s, Н-4); 7.53 (2Н, d, J = 8.4, H-2,6 Ar); 8.18 (2Н, d, J = 8.4, H-3,5 Ar); 9.14 (1Н, br. s, NH); 10.10 (1Н, br. s, NH)

1j

3253 (NH), 2190 (С ≡ N), 1650 (С = О), 1638 (C = N)

1.76 (3Н, s, СН3); 5.43 (1Н, s, Н-4); 7.21-7.52 (9Н, m, H Ar); 9.00 (1Н, br. s, NH); 9.97 (1Н, br. s, NH)

1k

3196 (NH), 2197 (С ≡ N), 1652 (С = О), 1633 (C = N)

1.72 (3Н, s, СН3); 5.81 (1Н, s, Н-4); 7.22-7.55 (9Н, m, H Ar); 8.92 (1Н, br. s, NH); 10.00 (1Н, br. s, NH)

1l

3217 (NH), 2204 (С ≡ N), 1732 (С = О), 1667 (C = N)

2.31 (3Н, s, СН3); 3.55 (3Н, s, ОСН3); 5.71 (1Н, s, Н-4); 7.23-7.44 (4Н, m, H Ar); 9.03 (1Н, br. s, NH); 10.12 (1Н, br. s, NH)

1m

3243 (NH), 2202 (С ≡ N), 1704 (С = О), 1637 (C = N)

2.32 (6Н, s, 2СН3); 3.58 (3Н, s, ОСН3); 5.22 (1Н, s, Н-4); 7.04-7.17 (4Н, m, H Ar); 8.89 (1Н, br. s, NH); 9.93 (1Н, br. s, NH)

1n

3250 (NH), 2208 (С ≡ N), 1717 (С = О), 1634 (C = N)

2.31 (3Н, s, СН3); 3.58 (3Н, s, ОСН3); 3.77 (3Н, s, ОСН3); 5.22 (1Н, s, Н-4); 6.82 (2Н, d, J = 8.7, H-2,6 Ar); 7.18 (2Н, d, J = 8.7, H-3,5 Ar); 8.87 (1Н, br. s, NH); 9.92 (1Н, br. s, NH)

1,3-Dibenzyl-2-cyanoimino-5-ethoxycarbonyl-6-methyl-4-(4-methylphenyl)-1,2,3,4-tetrahydropyri-midine (3a). Cyanoiminopyrimidine 1b (1.49 g, 5 mmol) was dissolved in a mixture of a 1 M solution of NaOMe in MeOH (5 ml) and of anhydrous DMF (7 ml). The solution was evaporated on a rotary evaporator until the entire methanol was distilled off, and benzyl chloride (1.73 ml, 15 mmol) was added to the remaining solution. The obtained solution was refluxed for 6 h and after cooling was evaporated on a rotary evaporator. The residue was treated with petroleum ether (0 °C) (5 ml) until a suspension had formed, filtered, and recrystallized from EtOH. Yield 0.765 g (32 %). Colorless crystals; mp 187-188 °C. IR spectrum, ν, cm-1: 2202 (С ≡ N), 1722 (С = О), 1556 (C = N). 1 H NMR spectrum, δ, ppm (J, Hz): 1.12 (3 H, t, 3J = 7.0, CH 3CH2); 2.34 (3 H, s, CH3); 2.36 (3 H, s, CH3); 4.05 (2 H, q, 3J = 7.0, СH3CH 2); 4.69 (1Н, d, 2J = 15.4) and 4.88 (1Н, d, 2J = 15.4, СН2Ph); 5.30 (1Н, d, 2J = 15.3) and 5.60 (1Н, d, 2J = 15.3, СН2Ph); 5.41 (1Н, s, Н-4); 6.74 (2 H, d, 3J = 7.2, H-2,6 Ar); 6.98 (2 H, d, 3J = 7.2, H-3,5 Ar); 7.03-7.45 (10 H, m, H Ph). Found, %: С 75.18; Н 6.39; N 11.70. C30H30N4O2. Calculated, %: С 75.29; Н 6.32; N 11.71.

1,3-Dibenzyl-4-(4-chlorophenyl)-2-cyanoimino-5-ethoxycarbonyl-6-methyl-1,2,3,4-tetrahydro-pyrimidine (3b). The compound was obtained similarly. Yield 0.724 g (29 %); mp 167-168 °C. IR spectrum, ν, cm-1: 2206 (С ≡ N), 1711 (С = О), 1568 (C = N). 1 H NMR spectrum, δ, ppm (J, Hz): 1.13 (3 H, t, 3J = 7.0, CH 3CH2); 2.38 (3 H, s, CH3); 4.06 (2 H, q, 3J = 7.0, СH3CH 2); 4.70 (1Н, d, 2J = 15.3) and 4.84 (1Н, d, 2J = 15.3, СН2Ph); 5.35 (1Н, d, 2J = 16.3) and 5.58 (1Н, d, 2J = 16.3, СН2Ph); 5.42 (1Н, s, Н-4); 6.69 (2 H, d, 3J = 7.2, H-2,6 Ar); 7.02-7.39 (12 H, m, H-3,5 Ar, H Ph). Found, %: С 69.88; Н 5.40; N 11.28. C29H27ClN4O2. Calculated, %: С 69.80; Н 5.45; N 11.23.

Ethyl 2-(Carbamoylamino)-4-methyl-6-(4-methylphenyl)pyrimidine-5-carboxylate (4a). A mixture of cyanoiminopyrimidine 1b (0.120 g, 0.4 mmol) and MnO2 (0.35 g, 4 mmol) in acetone (15 ml) was refluxed for 20 h and was filtered off after cooling. The precipitate was washed on the filter with acetone (30 ml), and the combined filtrates were evaporated. The residue was recrystallized from acetone. Yield 0.098 g (78 %). Colorless crystals; mp 201-202 °C. IR spectrum, ν, cm-1: 3416 (NH2), 3199 (NH), 1713 (С = О (ester)), 1693 (CONH2), 1552 (C = N). 1 H NMR spectrum, δ, ppm (J, Hz): 1.05 (3 H, t, J = 7.1, CH 3CH2); 2.32 (3 H, s, CH 3С6Н4); 2.42 (3 H, s, 6-CH3); 4.10 (2 H, q, J = 7.1, СH3CH 2); 6.89 (1 H, br. s) and 8.43 (1 H, br. s, NH2); 7.25 (2 H, d, J = 8.0, H-2,6 Ar); 7.45 (2 H, d, J = 8.0, H-3,5 Ar); 9.11(1 H, s, NH). Found, %: С 61.22; Н 5.68; N 17.83. C16H18N4O3. Calculated, %: С 61.14; Н 5.77; N 17.82.

Ethyl 2-(Carbamoylamino)-6-(4-chlorophenyl)-4-methylpyrimidine-5-carboxylate (4b). The compound was obtained similarly. Yield 0.094 g (70 %); mp 219-220 °C. IR spectrum, ν, cm-1: 3348 (NH2), 3258 (NH), 1711 (С = О (ester)), 1694 (CONH2), 1561 (C = N). 1 H NMR spectrum, δ, ppm (J, Hz): 1.08 (3 H, t, J = 7.1, CH 3CH2); 2.50 (3 H, s, CH3); 4.13 (2 H, q, J = 7.1, СH3CH 2); 6.88 (1 H, br. s) and 8.31 (1 H, br. s, NH2); 7.47 (2 H, d, J = 8.4, H-2,6 Ar); 7.56 (2 H, d, J = 8.4, H-3,5 Ar); 9.21 (1 H, s, NH). Found, %: С 53.77; Н 4.59; N 16.70. C15H15ClN4O3. Calculated, %: С 53.82; Н 4.52; N 16.74.

Ethyl 2-Amino-4-methyl-6-(4-methylphenyl)pyrimidine-5-carboxylate (5a). A mixture of cyano-iminopyrimidine 1b (0.45 g, 1.5 mmol) and MnO2 (1.31 g, 15 mmol) in o-xylene (50 ml) was refluxed for 26 h and filtered. The precipitate was washed on the filter with hot o-xylene (20 ml), and the combined filtrates were evaporated. The residue was treated with petroleum ether (10 ml) (at 0 °C) until a suspension was formed, filtered off, and recrystallized from EtOH. Yield 0.130 g (32 %). Colorless crystals; mp 135-136 °C. IR spectrum, ν, cm-1: 3458, 3314 (NH2), 1705 (С = О), 1668 (NH2), 1538 (C = N). 1 H NMR spectrum, δ, ppm (J, Hz): 0.97 (3 H, t, J = 7.1, CH 3CH2); 2.38 (3 H, s, CH3С6Н4); 2.40 (3 H, s, 6-CH3); 3.99 (2 H, q, J = 7.1, СH3CH 2); 6.41 (2 H, s, NH2); 7.16 (2 H, d, J = 7.8, H-2,6 Ar); 7.38 (2 H, d, J = 7.8, H-3,5 Ar). Found, %: С 66.32; Н 6.27; N 15.58. C15H17N3O2. Calculated, %: С 66.40; Н 6.32; N 15.49.

Ethyl 2-Amino-6-(4-chlorophenyl)-4-methylpyrimidine-5-carboxylate (5b). The compound was obtained similarly. Yield 0.131 g (30 %). Colorless crystals; mp 160 °C. IR spectrum, ν, cm-1: 3424, 3312 (NH2), 1700 (С = О), 1643 (NH2), 1531 (C = N). 1 H NMR spectrum, δ, ppm (J, Hz): 1.01 (3 H, t, J = 6.9, CH 3CH2); 2.39 (3 H, s, 6-CH3); 4.01 (2 H, q, J = 6.9, СH3CH 2); 6.61 (2 H, s, NH2); 7.39 (2 H, d, J = 7.9, H-2,6 Ar); 7.47 (2 H, d, J = 7.9, H-3,5 Ar). Found, %: С 57.67; Н 4.92; N 14.31. C14H14ClN3O2. Calculated, %: С 57.64; Н 4.84; N 14.40.

The work was carried out with financial support from the Federal Target Program of the Ministry of Education and Science of the Russian Federation "Scientific and Scientific-pedagogical Personnel of Innovative Russia" in 2009-2013 (State contract No. 14.740.11.0368) and the Ministry of Education and Science of the Russian Federation Analytical Target Program "Development of the Higher School Scientific Potential (2009-2011)" (Project No. 2.11/11994).

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Copyright information

© Springer Science+Business Media, Inc. 2012

Authors and Affiliations

  • A. H. Moustafa
    • 1
  • A. S. Shestakov
    • 1
  • Kh. S. Shikhaliev
    • 1
  1. 1.Voronezh State UniversityVoronezhRussia

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