Pyrido[1,2-a]pyrimidines are among the privileged entities for drug discovery. They are inhibitors of enzymes elastase, reductase, urease, monoamine oxidase, and others which regulate the functioning of living systems in health and disease.1 This causes pyrido[1,2-a]pyrimidines to manifest a wide spectrum of biological action, in particular antiviral, antimicrobial, antitumor, antipsychotic, and antioxidant activity.2 Research on the chemistry of these compounds and the search for effective methods for the synthesis of their new derivatives for the creation of promising pharmaceutical substances remains of steady interest.3

One of the convenient approaches to the construction of the pyrido[1,2-a]pyrimidine system is based on the heterocyclization of the available 1,1-bis(1H-benzotriazol-1-yl)- 3,4,4-trichloro-2-nitrobuta-1,3-diene (1) by the action of 2-aminopyridine (2). As a result of the reaction, 4-(dichloromethylidene)-3-nitro-4H-pyrido[1,2-a]pyrimidine 3 containing a benzotriazole fragment in position 2 of the pyrido[1,2-a]pyrimidine system is formed.4 In the study of the generality of this synthetic approach, we found that the reaction of 2-aminopyridine (2) with 3,4,4-trichloro-1,1-bis-(3,5-dimethyl-1H-pyrazol-1-yl)-2-nitrobuta-1,3-diene (4) proceeds differently and leads to the formation of 4-(dichloromethylidene)- 3-nitro-4H-pyrido[1,2-a]pyrimidine 5 containing not the dimethylpyrazole fragment at position 2, as might be expected by analogy with benzotriazole derivatives, but the 2-aminopyridine fragment5 (Scheme 1).

scheme 1

Scheme 1

Apparently, 3,5-dimethylpyrazole is a better leaving group than benzotriazole, and under the reaction conditions it is substituted by the 2-aminopyridine fragment.

To test this assumption, we decided to investigate the heterocyclization of 3,4,4-trichloro-2-nitrobuta-1,3-diene derivatives 6a–d, in the molecules of which one of the dimethylpyrazole fragments is replaced by an arylamine fragment such as p-anisidine, phenetidine, 4-phenoxyaniline, or 4-bromoaniline. These arylamines are not good leaving groups, therefore we expected that they would not participate in the reaction and would transfer to the structures of the resulting pyrido[1,2-a]pyrimidines. This approach may open a convenient route to the synthesis of 2-arylamino-substituted 4-(dichloromethylidene)-3-nitro-4H-pyrido[1,2-a]pyrimidines. The preparation of 3,4,4-trichloro-1-(4-methoxyanilino)-1-(3,5-dimethyl-1H-pyrazol-1-yl)-2-nitrobuta-1,3-diene (6a) and 3,4,4-trichloro-1-(3,5-dimethyl-1H-pyrazol-1-yl)-1-(4-ethoxyanilino)-2-nitrobuta-1,3-diene (6b) was described earlier.6 4-Phenoxy- and 4-bromo derivatives 6c,d were obtained similarly by the action of 4-phenoxyaniline (7c) or 4-bromoaniline (7d) on substituted buta-1,3-diene 4. The synthesized 1-arylamino-1,3-butadienes 6a–d (Scheme 2) were then reacted with 2-aminopyridine (8a) and 2-amino-4-methylpyridine (8b).

scheme 2

Scheme 2

We have previously shown that the reaction of compound 4 and its bisbenzotriazole analog 1 with amines usually proceeds with the successive substitution of one or both azole groups by amine fragments.6 One might expect that in the case of the reaction of buta-1,3-dienes 6a–d with 2-aminopyridine (8a) and 2-amino-4-methylpyridine (8b) the process would be completed at the step of the formation of the corresponding 1-(2-aminopyridino)-1-arylamino-3,4,4-trichloro-2-nitrobuta-1,3-dienes. However, the reaction proceeded differently with the participation of the trichlorovinyl group and led to the formation of 4-(di-chloromethylidene)-3-nitro-4H-pyrido[1,2-a]pyrimidines 9a–h containing the fragment of the corresponding arylamine in position 2 in 55–85% yields (Scheme 2). 1-(2-Aminopyridino)-1-arylamino-3,4,4-trichloro-2-nitrobuta-1,3-dienes were not detected in the reaction mixtures.

Taking into account previously published data on the reactivity of 1,1,2,4,4-pentachloro-2-nitrobuta-1,3-diene derivatives and the possibility of sequential substitution of terminal and internal chlorine atoms in their molecules with the formation of heterocyclic structures,7 we suggested the following mechanism for the formation of 2-arylaminosubstituted 4-(dichloromethylidene)-3-nitro-4H-pyrido[1,2-a]-pyrimidines 9a–h. In the first steps, the dimethylpyrazole fragment in compound 6 is substituted by the aminopyridine fragment via addition–elimination reactions. As we have already noted, such processes are characteristic of 1,1-bisazolyl-3,4,4-trichloro-2-nitrobuta-1,3-dienes and their derivatives.6 Next, the isomerization of the aminopyridine fragment into the iminodihydropyridine fragment takes place, followed by intramolecular heterocyclization of compound 10 via nucleophilic addition and elimination of HCl with the formation of a polysubstituted pyrido[1,2-a]-pyrimidine system (Scheme 3).

scheme 3

Scheme 3

The obtained compounds were identified based on the data of IR spectroscopy, 1H, 13C NMR spectroscopy, mass spectrometry, and elemental analysis. In the IR spectra of the starting 1-arylamino-3,4,4-trichloro-1-(3,5-dimethyl-1H-pyrazol-1-yl)-2-nitrobuta-1,3-dienes 6c,d and pyrido- [1,2-a]pyrimidines 9a–h there are broadened absorption bands in the region of 3175–3255 cm–1 related to the stretching vibrations of the N–H bonds of the secondary amino groups, as well as absorption bands of stretching vibrations of the C=N and C=C bonds in the 1474–1649 cm–1 range. The bands of symmetric vibrations with frequencies of 1366–1387 cm–1 and antisymmetric vibrations with frequencies of 1559–1593 cm–1 are characteristic to nitro groups. It is interesting to note that in the 1H NMR spectrum of the starting 3,4,4-trichloro-1-(3,5-dimethyl-1H-pyrazol-1-yl)-2-nitro-1-(4-phenoxyanilino)buta-1,3-diene (6c) one of the methyl groups appears as two singlets, whereas in the 13C NMR spectrum, in addition to doubling of the signal of this methyl group, there is also a doubling of the signal of the CH group of the pyrazole ring and one of the CH groups of the aromatic fragment, which, apparently, is explained by the influence of the second phenyl ring, since no doubling of signals is observed in the 1H and 13C NMR spectra of compounds 6a,b,d.

The mass spectra of compounds 6c and 9a–f contain groups of molecular ion peaks in which the ratio of the intensities of the isotopic components indicates the presence of three chlorine atoms in the molecule of buta-1,3-diene 6c (the ratio of intensities is 100:98:32:3.5), whereas in molecules of pyrido[1,2-a]pyrimidines 9a–f there are two chlorine atoms (intensity ratio of 100:65:1.1). In the mass spectra of compounds 6d and 9g,h the groups of molecular ion peaks have a more complex multiplicity due to the presence of bromine isotopes, but the intensity ratio of the isotopic components corresponds to three chlorine atoms and one bromine atom for the starting compound 6d and one bromine atom and two chlorine atoms for pyrido[1,2-a]pyrimidines 9g,h.8

We were able to obtain single crystals of 4-(dichloromethylidene)-N-(4-ethoxyphenyl)-8-methyl-3-nitro-4H-pyrido- [1,2-a]pyrimidin-2-amine (9d), and perform X-ray structural analysis. It was found that compound 9d crystallizes in the \( P\overline{1} \)ˉ‾ triclinic space group with two molecules in the unit cell and one molecule in the asymmetric cell (Fig. 1).

Figure 1.
figure 1

Molecular structure of compound 9d with atoms represented as thermal vibration ellipsoids of 50% probability.

Full size image

To conclude, a convenient approach for the preparation of various 2-arylamino-substituted 4-(dichloromethylidene)- 3-nitro-4H-pyrido[1,2-a]pyrimidines has been developed based on the accessible 3,4,4-trichloro-1,1-bis(3,5-dimethyl-1H-pyrazol-1-yl)-2-nitrobuta-1,3-diene.

Experimental

IR spectra were registered on a Thermo Niсolet Protege 460 FT-IR spectrometer in KBr pellets. 1H and 13C NMR spectra were acquired on a Bruker Avance 500 spectrometer (500 and 125 MHz, respectively) in CDCl3 (compounds 6c,d, 9a–f, and 9h) or in DMSO-d6 (compound 9g). Residual solvent signals (CDCl3: 7.26 ppm for 1H nuclei, 77.2 ppm for 13С nuclei; DMSO-d6: 2.50 ppm for 1H nuclei, 40.1 ppm for 13С nuclei) were used as the internal standard. The assignment of signals in the 13C NMR spectra was performed using the DEPT procedure. Chromato-mass spectrometry was performed on an Agilent 1200 system with an Agilent 6410 Triple Quad with mass selective detector with electrospray ionization (ESI+, MS2 scanning mode). Agilent ZORBAX Eclipse XDB-C18 (4.6 × 50 mm, 1.8 μm) column. Mobile phase – MeCN–H2O + 0.05% HCO2H, gradient elution from 40 to 90% MeCN over 10 min, 0.5 ml/min flow rate. Elemental analysis was performed on a Vario MICRO cube CHNSanalyzer. Halogen content was determined by classical microanalysis according to the modified Pregl's method.9 Melting points were determined on a Kofler bench. Monitoring of the reaction progress and assessment of the purity of synthesized compounds were done by TLC on Merck Millipore Silica gel 60 F254 plates, eluent Et2O, visualization with iodine vapor.

Reagents and solvents were supplied by Sigma-Aldrich and Merck and were used without additional purification. The starting buta-1,3-dienes 6a,b were synthesized by a published method.6

Synthesis of buta-1,3-dienes 6c,d (General method). Amine 7c,d (4.5 mmol) was added to a suspension of 3,4,4-trichloro-1,1-bis(3,5-dimethyl-1H-pyrazol-1-yl)-2-nitrobuta-1,3-diene (4) (1.78 g, 4.5 mmol) in Et2O (20 ml), and the mixture was stirred at room temperature for 24 h, then kept at –5°С for 12 h. The precipitate was filtered off, washed with cold Et2O (10 ml) followed by H2O (20 ml), and dried under reduced pressure. The obtained compounds 6c,d were used further without additional purification.

(E)-N-[3,4,4-Trichloro-1-(3,5-dimethyl-1H-pyrazol-1-yl)-2-nitrobuta-1,3-dien-1-yl]-4-phenoxyaniline (6c). Yield 1.55 g (72%), yellow crystals, mp 118–119°С. IR spectrum, ν, cm–1: 3208 (NH), 3058, 1622, 1593 (NO2), 1577, 1570, 1504, 1488, 1413, 1380 (NO2), 1370, 1271, 1247, 1180, 1163, 1117, 1070, 1022, 967, 866, 787, 692, 571. 1H NMR spectrum, δ, ppm (J, Hz): 1.94 and 1.95 (3Н, s, СН3); 2.27 (3Н, s, СН3); 5.89 (1Н, s, Н-4 pyrazole); 6.71 (2Н, d, J = 8.1, Н-2,6 Ph); 6.85 (2Н, d, J = 8.6, Н-2',6'); 6.97 (2Н, d, J = 8.9, Н-3',5'); 7.14 (1Н, t, J = 7.4, Н-4 Ph); 7.34 (2Н, t, J = 8.0, Н-3,5 Ph); 11.83 (1Н, s, NH). 13C NMR spectrum, δ, ppm: 11.0, 11.6 (СН3); 13.7 (СН3); 106.0; 108.9, 109.9 (С-4 pyrazole); 119.3 (2CН Ar); 119.5 (2CН Ar); 123.6, 123.7 (2CН Ar); 124.3 (CН Ar); 130.1 (2CН Ar); 130.5; 141.6; 141.9; 148.7; 148.8; 152.9; 156.2; 156.6. Mass spectrum, m/z (Irel, %): 979 [2M+Na]+ (12), 501 [M+Na]+ (18), 405 (100). Found, %: C 52.67; H 3.62; Cl 22.02; N 11.65. C21H17Cl3N4O3. Calculated, %: C 52.58; H 3.57; Cl 22.17; N 11.68.

(E)-4-Bromo-N-[3,4,4-trichloro-1-(3,5-dimethyl-1Hpyrazol-1-yl)-2-nitrobuta-1,3-dien-1-yl]aniline (6d). Yield 1.20 g (57%), yellow crystals, mp 119–120°С. IR spectrum, ν, cm–1: 3255 (NH), 2926, 1621, 1594, 1567 (NO2), 1487, 1473, 1437, 1400, 1371 (NO2), 1283, 1270, 1173, 1114, 1069, 1010, 975, 935, 872, 829, 809, 703, 637, 598, 548, 497. 1H NMR spectrum, δ, ppm (J, Hz): 1.92 (3Н, s, СН3); 2.29 (3Н, s, СН3); 5.90 (1Н, s, H-4 pyrazole); 6.60 (2Н, d, J = 8.6, Н-2',6'); 7.37 (2Н, d, J = 8.6, Н-3',5'); 11.65 (1Н, s, NH). 13C NMR spectrum, δ, ppm: 11.6 (СН3); 13.7 (СН3); 100.0; 109.2; 110.2 (С-4 pyrazole); 120.7; 123.6 (2CН Ar); 126.0; 133.0 (2CН Ar); 135.0; 141.8; 148.4; 153.3. Mass spectrum, m/z (Irel, %): 487 [M+Na]+ (22), 465 [M+H]+ (43), 301 (100). Found, %: C 38.77; H 2.74; Hal 39.65; N 12.12. C15H12BrCl3N4O2. Calculated, %: C 38.62; H 2.59; Hal 39.93; N 12.01.

Synthesis of pyrido[1,2-a]pyrimidines 9a–h (General method). Aminopyridine 8a,b (9 mmol) was added to a solution of substituted (E)-N-[3,4,4-trichloro-1-(3,5-dimethyl-1H-pyrazol-1-yl)-2-nitrobuta-1,3-dien-1-yl]aniline 6a–d (3 mmol) in THF (30 ml). The reaction mixture was stirred at 20°С for 18 h, then poured into H2O (200 ml). The precipitate was filtered off, washed with H2O (2×10 ml) and MeOH (1×10 ml), and dried under reduced pressure. The crude product was heated under reflux in CHCl3 (20 ml) until complete dissolution. The solvent was evaporated under reduced pressure, and the residue was purified by column chromatography (SiO2, eluent Et2O).

4-(Dichloromethylidene)-N-(4-methoxyphenyl)-3-nitro-4H-pyrido[1,2-a]pyrimidin-2-amine (9a). Yield 0.70 g (61%), orange crystals, mp 141–143°С (decomp.). IR spectrum, ν, cm–1: 3227 (NH), 3115, 3092, 3047, 3006, 2962, 2915, 2838, 1635, 1607, 1595, 1562 (NO2), 1545, 1510, 1479, 1465, 1438, 1390, 1372 (NO2), 1274, 1244, 1201, 1169, 1149, 1120, 1089, 1023, 877, 828, 755, 700, 614, 550. 1H NMR spectrum, δ, ppm (J, Hz): 3.82 (3Н, s, ОСН3); 6.84 (1Н, t, J = 6.7, Н Ar); 6.90 (2Н, d, J = 8.8, Н-2',6'); 7.17 (1Н, d, J = 8.8, Н Ar); 7.56 (2Н, d, J = 8.8, Н-3',5'); 7.64 (1Н, t, J = 7.6, Н Ar); 8.02 (1Н, d, J = 6.6, Н Ar); 11.47 (1Н, s, NH). 13C NMR spectrum, δ, ppm: 55.6 (ОСН3); 103.4; 114.8 (CН Ar); 114.2 (2CН Ar); 118.3; 123.2 (CН Ar); 124.7 (2CН Ar); 126.6; 130.2; 136.2 (CН Ar); 140.0 (CН Ar); 152.4; 153.6; 157.4. Mass spectrum, m/z (Irel, %): 779 [2M+Na]+ (25), 401 [M+Na]+ (12), 379 [M+H]+ (100). Found, %: C 50.69; H 3.27; Cl 18.57; N 14.62. C16H12Cl2N4O3. Calculated, %: C 50.68; H 3.19; Cl 18.70; N 14.78.

4-(Dichloromethylidene)-N-(4-methoxyphenyl)-8-methyl-3-nitro-4H-pyrido[1,2-a]pyrimidin-2-amine (9b). Yield 0.80 g (68%), orange crystals, mp 148–150°С (decomp.). IR spectrum, ν, cm–1: 3175 (NH), 3114, 3062, 2979, 2929, 2886, 1637, 1595, 1563 (NO2), 1543, 1486, 1425, 1376 (NO2), 1347, 1299, 1270, 1244, 1197, 1162, 1144, 1120, 1088, 1049, 1027, 974, 929, 834, 771, 757, 708, 680, 632, 562. 1H NMR spectrum, δ, ppm (J, Hz): 2.38 (3Н, s, СН3); 3.82 (3Н, s, ОСН3); 6.68 (1Н, dd, J = 7.0, J = 1.9, Н Ar); 6.90 (2Н, d, J = 9.0, Н-2',6'); 6.98 (1Н, s, Н Ar); 7.57 (2Н, d, J = 9.0, Н-3',5'); 7.92 (1Н, d, J = 7.0, Н Ar); 11.48 (1Н, s, NH). 13C NMR spectrum, δ, ppm: 21.9 (СН3); 55.6 (ОСН3); 103.6; 114.2 (2CН Ar); 115.2 (CН Ar); 117.9; 121.8 (CН Ar); 124.6 (2CН Ar); 126.6; 130.4; 135.3 (CН Ar); 152.1; 153.1; 153.9; 157.3. Mass spectrum, m/z (Irel, %): 807 [2M+Na]+ (14), 393 [M+H]+ (100). Found, %: C 52.03; H 3.79; Cl 17.87; N 14.14. C17H14Cl2N4O3. Calculated, %: C 51.93; H 3.59; Cl 18.03; N 14.25.

4-(Dichloromethylidene)-N-(4-ethoxyphenyl)-3-nitro-4H-pyrido[1,2-a]pyrimidin-2-amine (9c). Yield 0.87 g (74%), yellow crystals, mp 136–138°С (decomp.). IR spectrum, ν, cm–1: 3195 (NH), 3145, 3083, 3057, 3000, 2964, 2854, 1649, 1580 (NO2), 1552, 1503, 1492, 1434, 1414, 1370 (NO2), 1342, 1303, 1284, 1245, 1191, 1164, 1108, 1066, 1039, 1003, 936, 858, 828, 796, 745. 1H NMR spectrum, δ, ppm (J, Hz): 1.42 (3Н, t, J = 7.0, СН2СН3); 4.04 (2Н, q, J = 7.0, СН2СН3); 6.83 (1Н, td, J = 6.8, J = 1.2, Н Ar); 6.89 (2Н, d, J = 9.0, Н-2',6'); 7.17 (1Н, d, J = 8.8, Н Ar); 7.55 (2Н, d, J = 9.0, Н-3',5'); 7.60–7.66 (1Н, m, Н Ar); 8.02 (1Н, dd, J = 6.8, J = 0.8, Н Ar); 11.47 (1Н, s, NH). 13C NMR spectrum, δ, ppm: 15.0 (СН2СН3); 63.8 (СН2СН3); 103.4; 112.8 (CН Ar); 114.8 (2CН Ar); 118.2; 123.2 (CН Ar); 124.7 (2CН Ar); 126.7; 130.1; 136.2 (CН Ar); 140.0 (CН Ar); 152.4; 153.6; 156.8. Mass spectrum, m/z (Irel, %): 807 [2M+Na]+ (55), 415 [M+Na]+ (28), 393 [M+H]+ (100). Found, %: C 52.12; H 3.65; Cl 18.00; N 14.20. C17H14Cl2N4O3. Calculated, %: C 51.93; H 3.59; Cl 18.03; N 14.25.

4-(Dichloromethylidene)-N-(4-ethoxyphenyl)-8-methyl-3-nitro-4H-pyrido[1,2-a]pyrimidin-2-amine (9d). Yield 0.93 g (76%), yellow crystals, mp 157–159°С (decomp.). IR spectrum, ν, cm–1: 3221 (NH), 3126, 2977, 2926, 1642, 1566 (NO2), 1541, 1493, 1475, 1458, 1426, 1383 (NO2), 1353, 1272, 1248, 1198, 1162, 1090, 1050, 1011, 980, 882, 869, 818, 797, 755, 616, 529. 1H NMR spectrum, δ, ppm (J, Hz): 1.40 (3Н, t, J = 7.0, СН2СН3); 2.37 (3Н, s, OСН3); 4.02 (2Н, q, J = 7.0, СН2СН3); 6.68 (1Н, dd, J = 7.0, J = 1.8, Н Ar); 6.88 (2Н, d, J = 9.0, Н-2',6'); 6.97 (1Н, s, Н Ar); 7.55 (2Н, d, J = 9.0, Н-3',5'); 7.91 (1Н, d, J = 7.0, Н Ar); 11.47 (1Н, s, NH). 13C NMR spectrum, δ, ppm: 15.0 (СН2СН3); 21.8 (OСН3); 63.8 (СН2СН3); 103.6; 114.7 (2CН Ar); 115.2 (CН Ar); 117.8; 121.7 (CН Ar); 124.5 (2CН Ar); 126.6; 130.2; 135.2 (CН Ar); 152.0; 153.1; 153.7; 156.6. Mass spectrum, m/z (Irel, %): 407 [M+H]+ (100). Found, %: C 53.32; H 4.05; Cl 17.15; N 13.79. C18H16Cl2N4O3. Calculated, %: C 53.09; H 3.96; Cl 17.41; N 13.76.

4-(Dichloromethylidene)-3-nitro-N-(4-phenoxyphenyl)-4H-pyrido[1,2-a]pyrimidin-2-amine (9e). Yield 0.73 g (55%), yellow crystals, mp 143–145°С (decomp.). IR spectrum, ν, cm–1: 3189 (NH), 3118, 3100, 3054, 2921, 2854, 1636, 1594, 1559 (NO2), 1542, 1487, 1419, 1393, 1374 (NO2), 1347, 1272, 1248, 1196, 1166, 1145, 1122, 1088, 876, 773, 750, 710, 688, 498. 1H NMR spectrum, δ, ppm (J, Hz): 6.87 (1Н, td, J = 6.9, J = 1.4, Н Ar); 7.00–7.06 (4Н, m, Н Ar); 7.12 (1Н, tt, J = 7.4, J = 1.1, Н Ar); 7.20 (1Н, dq, J = 9.0, J = 0.7, Н Ar); 7.35 (1Н, d, J = 7.4, Н Ar); 7.36 (1Н, d, J = 7.4, Н Ar); 7.62–7.69 (3Н, m, Н Ar); 8.05 (1Н, dq, J = 6.8, J = 0.7, Н Ar); 11.54 (1Н, s, NH). 13C NMR spectrum, δ, ppm: 103.5; 113.0 (CН Ar); 118.4; 119.1 (2CН Ar); 119.2 (2CН Ar); 123.2 (CН Ar); 123.6 (CН Ar); 124.6 (2CН Ar); 126.6; 130.0 (2CН Ar); 132.6; 136.3 (CН Ar); 140.1 (CН Ar); 152.4; 153.7; 154.8; 157.3. Mass spectrum, m/z (Irel, %): 905 (100), 903 [2M+Na]+ (70), 463 [M+Na]+ (51), 441 [M+H]+ (79). Found, %: C 57.35; H 3.27; Cl 15.91; N 12.64. C21H14Cl2N4O3. Calculated, %: C 57.16; H 3.20; Cl 16.07; N 12.70.

4-(Dichloromethylidene)-8-methyl-3-nitro-N-(4-phenoxyphenyl)-4H-pyrido[1,2-a]pyrimidin-2-amine (9f). Yield 0.85 g (62%), yellow crystals, mp 187–189°С (decomp.). IR spectrum, ν, cm–1: 3182 (NH), 3068, 3055, 3036, 2953, 2922, 2853, 1645, 1613, 1602, 1575 (NO2), 1541, 1505, 1486, 1470, 1425, 1381, 1366 (NO2), 1359, 1343, 1319, 1289, 1271, 1250, 1232, 1199, 1184, 1169, 1155, 1125, 1088, 1071, 1037, 1020, 1013, 982, 967, 912, 886, 864, 832, 799, 756, 739, 699, 692, 648, 547, 515, 474. 1H NMR spectrum, δ, ppm (J, Hz): 2.41 (3Н, s, СН3); 6.70 (1Н, dd, J = 7.0, J = 1.9, Н Ar); 6.97–7.07 (5Н, m, Н Ar); 7.12 (1Н, tt, J = 7.4, J = 1.0, Н Ar); 7.35 (1Н, d, J = 7.4, Н Ar); 7.36 (1Н, d, J = 7.4, Н Ar); 7.65 (2Н, d, J = 9.0, Н Ar); 7.95 (1Н, d, J = 7.0, Н Ar); 11.55 (1Н, s, NH). 13C NMR spectrum, δ, ppm: 21.9 (СН3); 104.9; 115.4 (CН Ar); 117.8; 119.1 (2CН Ar); 119.3 (2CН Ar); 121.8 (CН Ar); 123.6 (CН Ar); 124.6 (2CН Ar); 127.0; 130.0 (2CН Ar); 132.6; 134.4 (CН Ar); 142.1; 153.2; 153.9; 155.5; 160.7. Mass spectrum, m/z (Irel, %): 931 [2M+Na]+ (16), 477 [M+Na]+ (47), 455 [M+H]+ (100). Found, %: C 58.23; H 3.54; Cl 15.31; N 12.11. C22H16Cl2N4O3. Calculated, %: C 58.04; H 3.54; Cl 15.57; N 12.31.

N-(4-Bromophenyl)-4-(dichloromethylidene)-3-nitro-4H-pyrido[1,2-a]pyrimidin-2-amine (9g). Yield 1.09 g (85%), yellow crystals, mp 145–147°С (decomp.). IR spectrum, ν, cm–1: 3244 (NH), 3122, 1636, 1603, 1561 (NO2), 1547, 1474, 1412, 1377 (NO2), 1342, 1272, 1247, 1208, 1158, 1122, 1090, 1072, 1035, 1005, 976, 935, 878, 829, 760, 747, 699, 543. 1H NMR spectrum, δ, ppm (J, Hz): 7.15 (1Н, td, J = 6.9, J = 1.4, Н Ar); 7.31 (1Н, d, J = 8.6, Н Ar); 7.54 (2Н, d, J = 8.6, Н-2',6'); 7.73 (2Н, d, J = 8.6, Н-3',5'); 7.92–8.00 (1Н, m, Н Ar); 8.59 (1Н, dd, J = 6.8, J = 0.7, Н Ar); 11.21 (1Н, s, NH). 13C NMR spectrum, δ, ppm: 103.0; 115.2 (CН Ar); 117.3; 117.5; 122.7 (CН Ar); 125.4 (2CН Ar); 127.4; 132.0 (2CН Ar); 137.5; 138.0 (CН Ar); 142.7 (CН Ar); 152.0; 153.5. Mass spectrum, m/z (Irel, %): 879 (100), 875 [2M+Na]+ (77), 449 [M+Na]+ (51), 427 [M+H]+ (45). Found, %: C 42.22; H 2.30; Hal 35.01; N 13.02. C15H9BrCl2N4O2. Calculated, %: C 42.09; H 2.12; Hal 35.23; N 13.09.

N-(4-Bromophenyl)-4-(dichloromethylidene)-8-methyl-3-nitro-4H-pyrido[1,2-a]pyrimidin-2-amine (9h). Yield 0.72 g (55%), yellow crystals, mp 146–148°С (decomp.). IR spectrum, ν, cm–1: 3241 (NH), 3118, 3083, 3055, 2923, 1643, 1607, 1560 (NO2), 1478, 1467, 1387 (NO2), 1358, 1338, 1269, 1242, 1205, 1178, 1092, 885, 828, 747, 505. 1H NMR spectrum, δ, ppm (J, Hz): 2.42 (3Н, s, СН3); 6.74 (1Н, dd, J = 7.0, J = 1.7, Н Ar); 7.03 (1Н, s, Н Ar); 7.47 (2Н, d, J = 8.8, Н-2',6'); 7.60 (2Н, d, J = 8.8, Н-3',5'); 7.97 (1Н, d, J = 7.0, Н Ar); 11.55 (1Н, s, NH). 13C NMR spectrum, δ, ppm: 22.0 (СН3); 103.6; 109.1; 115.7 (CН Ar); 118.2; 121.8 (CН Ar); 124.4 (2CН Ar); 126.4; 132.0 (2CН Ar); 135.4 (CН Ar); 136.7; 151.9; 153.6; 153.9. Mass spectrum, m/z (Irel, %): 907 (100), 903 [2M+Na]+ (78), 463 [M+Na]+ (41), 441 [M+H]+ (59). Found, %: C 43.56; H 2.60; Hal 34.05; N 12.51. C16H11BrCl2N4O2. Calculated, %: C 43.47; H 2.51; Hal 34.11; N 12.67.

X-ray structural analysis of compound 9d was performed on a Bruker Smart APEX II diffractometer at 100 K using MoKα radiation (λ 0.71073 Å). The structure was solved by direct methods using the SIR2014 program10 and refined against F2 by the least-squares technique in the full-matrix anisotropic approximation using the SHELXL-2014 program.11 The positions of hydrogen atoms were calculated geometrically and refined according to the “rider” model with Uiso(H) = 1.5Ueq(C) for the methyl group and Uiso(H) = 1.2Ueq(C) for other groups. Molecular rendering was done using the PLATON software.12 The full set of

X-ray structural data was deposited at the Cambridge Crystallographic Data Center (deposit CCDC 2001089). Supplementary information file containing 1Н and 13С NMR spectra for compounds 6c,d and 9a–h as well as X-ray structural analysis data for compound 9d is available at the journal website at http://springerlink.bibliotecabuap.elogim.com/journal/10593.