Introduction

Imidazo[1,2-a]pyridines and pyrido[1,2-a]pyrimidines are an important privileged heterocyclic scaffold in numerous biologically active pharmacophores and their use as valuable building blocks for further synthetic transformations [1,2,3]. Some synthetic drugs that contain imidazo[1,2-a]pyridines core have been commercialized such as the anxiolytic alpidem(I), the anti-ulcer soraprazan(II), the sedative zolpidem(III), and the heart-failure drug olprinone(IV) (Fig. 1) [4,5,6,7,8,9,10]. Pyrido[1,2-a]pyrimidines structural motif is present in the tranquilizer pirenperone, the antiallergic agent ramastine(V), and anti-HIV-1 agents(VI) (Fig. 1) [11]. They are also used as synthetic intermediates or as additives to photographic materials and dyes [12]. The significance of these heterocycles has led to the development of new methods for their preparation. Huang et al. reported the synthesis of imidazo[1,2-a]pyridine and pyrido[1,2-a]pyrimidine derivatives using ketene aminals, the development of novel and efficient routes for rapid access to these compounds [13].

Fig. 1
figure 1

Biologically active tetrahydro-imidazo[1,2-a]pyridines and tetrahydropyrido[1,2-a]pyrimidines

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The reactions of heterocyclic ketene aminals (HKAs) with electron-deficient reagents offer a facile route to functionalized imidazo[1,2-a]pyridine and pyrido[1,2-a]pyrimidine derivatives [14,15,16]. HKAs are push–pull alkenes with the electron-withdrawing nitro and electron-donating amino groups [17, 18]. They are important building blocks in organic chemistry for synthesizing heterocyclic or fused heterocyclic compounds [19,20,21,22,23,24,25,26]. They are backbones also implement excellent biological roles and they exhibit pharmaceutical or insecticidal activity [27].

Coumarin derivatives are an important class of compounds that are used extensively in fields of medicine, biology, agriculture, and polymer science [28]. Heterocycles substituted at 3,4-position of the coumarin have also drawn special attention. The 3-cyanocoumarins are considered to be important compounds as they are required for the synthesis of methine dyes, 3-carboxycoumarins which are used for the synthesis of cephalospors, modified penicillins, and oxygen-bridged tetrahydropyridones [29].

Herein, we have developed simple synthesis of tetrahydro-imidazo[1,2-a]pyridines and tetrahydropyrido[1,2-a]pyrimidines derivatives via a one-pot reaction of various 1,n-diamines, nitro ketene dithioacetal [1,1-bis(methylthio)-2-nitroethene], various substituted salicylaldehydes, and malononitrile or alkyl cyanoacetate under catalyst-free conditions in ethanol.

Results and discussion

First, we used 1,1-bis(methylsulfanyl)-2-nitroethene (1a) with ethylenediamine (2a), salicylaldehyde (3a), and malononitrile (4a) as a model substrates to optimize the reaction conditions and different solvents and temperatures were investigated. The optimum reaction conditions were performed in EtOH without any catalyst (Table 1, entry 2).

Table 1 Optimisation conditions for the formation of 5a a
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With optimised conditions in hand, 1,1-bis(methylsulfanyl)-2-nitroethene 1, different kinds of diamines 2, various substituted salicylaldehydes 3, and malononitrile (4a) were used as substrates to synthesize the target compounds 5 and 6 (Table 2).

Table 2 Synthesis of compounds 5a–5h and 6i–6m
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The structures of compounds 5 and 6 were deduced from their IR, 1H NMR, 13C NMR, and mass spectroscopic data (see Supporting Information). For example, the 1H NMR spectrum of 5b clearly showed five singlets identified as amino groups (δ = 9.41 and 6.27 ppm), hydroxy (8.35 ppm), methine proton (4.89 ppm), and methoxy group (3.74 ppm), along with characteristic multiplets for two CH2 groups (3.74–4.10 ppm), and multiplets for the aromatic region (6.58–6.75 ppm). The methylene protons are non-equivalent, due to the methine carbon is an asymmetrical carbon atom and the two methylene groups are, therefore, diastereotopic. The 1H-decoupled 13C NMR spectrum of 5b indicated 15 distinct resonances, which confirmed the suggested structure. The mass spectrum of 5b displayed the molecular-ion peak at m/z = 329, in agreement with the proposed structure. The OH and amino proton resonance (at δ = 9.41, 8.35, and 6.27 ppm), disappeared after the addition of D2O to the DMSO solution of 5b. When we applied alkyl cyanoacetate 4b instead of malononitrile (4a), new 3-cyanocoumarin derivatives 7 were obtained in the same condition (Table 3).

Table 3 Synthesis of products 7a–7f
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Thermal gravimetry analysis

The TGA curves of 7a–7c showed thermal stability for these series of compounds that could be introduced as heat stable compounds (Fig. 2). Table 4 shows TGA data for 3-cyanocoumarin derivatives 7a–7c.

Fig. 2
figure 2

TG/DTA curve of 7a–7c

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Table 4 Comparison of thermal properties of 3-cyanocoumarin derivatives 7a–7c
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The structures of the products 7a–7c were characterized by IR, MS, 1H NMR, and 13C NMR spectra. For example, the IR spectrum of this compound showed absorption bands due to the NH, CN, CO, and NO2 groups at 3379, 2209, 1715, 1550, and 1326 cm−1. The 1H NMR spectrum of 7a recognized signals arising from methoxy (δ = 3.84 ppm), two methylene groups (3.82–4.16 ppm), and two amino groups (9.52 ppm ppm). The phenyl moiety gave rise to characteristic signals in the aromatic region of the spectrum. The 13C NMR spectrum of 7a showed 15 distinct signal resonances due to CCN, CNO2, and CN appearing at δ = 80.9, 115.7, and 118.6 ppm, respectively.

The formation of products 5 and 6 can be rationalized by the initial formation of intermediate 8a via Knoevenagel condensation of 3 and 4a. Subsequent addition of HKA 9 (formed from reaction of 1 with 2) to the intermediate 8a afforded intermediate 10. Intramolecular cyclization of 11 may proceed by attacking of the NH group to the ketenimine group and generate 5. The heterocyclic compound 5 is converted to 6 via air oxidation (Scheme 1). Based on these results, Michael addition of 8b to 9 gives intermediate 12, followed by air oxidation to afford product 7 (Scheme 2).

scheme 1
scheme 2

Conclusion

In summary, we achieved a one-pot, convenient, and catalyst-free synthesis of tetrahydroimidazo[1,2-a]pyridine and tetrahydropyrido[1,2-a]pyrimidines derivative. This reaction includes some important aspects like simple operation under mild conditions, easy accessibility of reactants and workup procedure, absence of catalysts, high atom economy, and the use of ethanol as a safe and nontoxic reaction medium. Moreover, this procedure has good yields without the column chromatography.

Experimental

All commercially available reagents were purchased from Fluka (Switzerland) and Merck (Germany) Chemical Co. and used without further purification. The NMR spectra were recorded with a Bruker DRX-300 Avance instrument (300 MHz for 1H and 75.4 MHz for 13C) with CDCl3 and DMSO-d 6 as solvent. Chemical shifts are given in ppm (δ) relative to internal TMS, and coupling constant (J) are reported in Hertz (Hz). Melting points were measured with an electrotherma1 9100 apparatus. Mass spectra were recorded with an Agilent 5975C VL MSD with Triple-Axis detector operating at an ionization potential of 70 eV. IR spectra were measured with Bruker Tensor 27 spectrometer.

General procedure for the preparation of compounds 5, 6, and 7

A mixture of 1,1-bis(methylsulfanyl)-2-nitroethene 1 (1 mmol) and 1,n-diamine 2 (1 mmol) in 5 cm3 EtOH was heated at reflux temperature for 3 h and monitored by thin-layer chromatography (TLC). Then, salicylaldehyde 3 (1 mmol) and malononitrile (4a) or alkyl cyanoacetate (4b) (1 mmol) was added to the reaction solution and the mixture was stirred at reflux for 3 h. Then, the mixture was cooled to r.t. and the precipitated product collected by filtration and washed with EtOH.

5-Amino-7-(2-hydroxyphenyl)-8-nitro-1,2,3,7-tetrahydroimidazo[1,2-a]pyridine-6-carbonitrile (5a, C14H13N5O3)

Yield: 0.254 g (85%); m.p.: 216–218 °C; 1H NMR (300 MHz, DMSO-d 6): δ = 9.43 (1H, s, NH), 9.25 (1H, s, OH), 6.96 (1H, t, 3 J HH = 6.6 Hz, Ar), 6.94 (1H, d, 3 J HH = 7.2 Hz, Ar), 6.67 (1H, d, 3 J HH = 8.4 Hz, Ar), 6.63 (1H, t, 3 J HH = 7.5 Hz, Ar), 6.30 (2H, s, NH2), 4.84 (1H, s, CH), 4.05–3.91 (1H, m, CH2N), 3.80–3.75 (2H, m, CH2NH) ppm; 13C NMR (75.4 MHz, DMSO-d 6): δ = 155.3 (CNN), 152.8 (C–OH), 150.0 (NCNH2), 130.9 (C of Ar), 129.5 (CH of Ar), 127.6 (CH of Ar), 121.6 (CH of Ar), 119.0 (CN), 115.8 (CH of Ar), 105.9 (CNO2), 59.0 (CCN), 45.1 (CH2N), 43.6 (CH2NH), 36.5 (CH) ppm; IR (KBr): \(\overline{v}\) = 3427, 3348, 3215, 2184, 1639, 1471, 1387, 1236, 1111 cm−1.

5-Amino-7-(2-hydroxy-3-methoxyphenyl)-8-nitro-1,2,3,7-tetrahydroimidazo[1,2-a]pyridine-6-carbonitrile (5b, C15H15N5O4)

Yield: 0.286 g (87%); m.p.: 236–238 °C; 1H NMR (300 MHz, DMSO-d 6): δ = 9.41 (1H, s, NH), 8.35 (1H, s, OH), 6.73 (1H, d, 3 J = 7.8 Hz, Ar), 6.63 (1H, t, 3 J = 7.8 Hz, Ar), 6.58 (1H, d, 3 J = 7.8 Hz, Ar), 6.27 (2H, s, NH2), 4.89 (1H, s, CH), 4.02–3.92 (2H, m, CH2N), 3.78 (2H, m, CH2NH), 3.74 (3H, s, OMe) ppm; 13C NMR (75.4 MHz, DMSO-d 6): δ = 152.7 (CNN), 150.0 (C–OH), 147.7 (C–OMe), 144.3 (NCNH2), 131.4 (C of Ar), 121.5 (CH of Ar), 121.3 (CH of Ar), 118.6 (CN), 110.1 (CH of Ar), 106.0 (CNO2), 58.9 (CCN), 56.1 (OMe), 45.0 (CH2N), 43.6 (CH2NH), 36.1 (CH) ppm; IR (KBr): \(\overline{v}\) = 3447, 3321, 3209, 2179, 1658, 1477, 1374, 1229, 1127 cm−1; MS (70 eV): m/z = 329 (M+, 4), 327 (15), 281 (100), 239 (11), 205 (16), 159 (10), 124 (19), 81 (11), 44 (10).

5-Amino-7-(2-hydroxyphenyl)-2-methyl-8-nitro-1,2,3,7-tetrahydroimidazo[1,2-a]pyridine-6-carbonitrile (5c, C15H15N5O3)

Mixture of two diastereoisomers. Yield: 0.253 g (81%); m.p.: 247–249 °C (dec.); IR (KBr): \(\overline{v}\) = 3563, 3345, 3223, 2180, 1650, 1463, 1364, 1227, 1113 cm−1.

Major isomer (70%): 1H NMR (300 MHz, DMSO-d 6): 9.54 (1H, s, NH), 9.25 (1H, s, OH), 6.98–6.92 (2H, m, ArH), 6.69–6.63 (2H, m, ArH), 6.26 (2H, s, NH2), 4.75 (1H, s, CH), 4.35–4.08 (1H, m, CH2), 3.67–3.62 (1H, m, CH2), 3.53–3.48 (1H, m, CH), 1.30 (3H, d, 3 J = 7.1 Hz, CH3) ppm; 13C NMR (75.4 MHz, DMSO-d 6): δ = 155.5 (CNN), 152.1 (C–OH), 150.0 (NCNH2), 130.5 (C of Ar), 129.9 (CH of Ar), 127.7 (CH of Ar), 121.7 (CN), 118.9 (CH of Ar), 115.9 (CH of Ar), 105.5 (CNO2), 58.8 (CCN), 52.5, 51.6 (2 CHN), 38.3 (CH), 21.3 (CH3) ppm.

Minor isomer (30%): 1H NMR (300 MHz, DMSO-d 6): 9.54 (1H, s, NH), 9.25 (1H, s, OH), 6.98–6.92 (2H, m, ArH), 6.69–6.63 (2H, m, ArH), 6.26 (2H, s, NH2), 4.82 (1H, s, CH), 4.14–3.98 (1H, m, CH2), 3.88–3.81 (1H, m, CH2), 3.53–3.48 (1H, m, CH), 1.30 (3H, d, 3 J = 7.1 Hz, CH3) ppm; 13C NMR (75.4 MHz, DMSO-d 6): δ = 155.6 (CNN), 151.6 (C–OH), 149.1 (NCNH2), 130.9 (C of Ar), 129.5 (CH of Ar), 127.7 (CH of Ar), 121.6 (CN), 118.8 (CH of Ar), 115.8 (CH of Ar), 105.6 (CNO2), 59.3 (CCN), 56.5, 50.4 (2 CHN), 37.4 (CH), 20.8 (CH3) ppm.

6-Amino-8-(2-hydroxyphenyl)-9-nitro-2,3,4,8-tetrahydro-1H-pyrido[1,2-a]pyrimidine-7-carbonitrile (5d, C15H15N5O3)

Yield: 0.269 g (86%); m.p.: 234–236 °C (dec.); 1H NMR (300 MHz, DMSO-d 6): δ = 11.58 (1H, s, NH), 9.35 (1H, s, OH), 6.70–6.63 (2H, m, ArH), 6.99–6.90 (2H, m, ArH), 6.21 (2H, s, NH2), 4.79 (1H, s, CH), 3.81–3.72 (2H, m, CH2N), 3.65–3.58 (2H, m, CH2NH), 2.20–1.80 (2H, m, CH2) ppm; 13C NMR (75.4 MHz, DMSO-d 6): δ = 155.5 (CNN), 151.8 (C–OH), 151.6 (NCNH2), 129.9 (C of Ar), 129.6 (CH of Ar), 127.8 (CH of Ar), 121.4 (CN), 119.0 (CH of Ar), 115.9 (CH of Ar), 108.1 (CNO2), 61.0 (CCN), 43.7 (CH2N), 38.8 (CH2NH), 36.4 (CH), 20.2 (CH2) ppm; IR (KBr): \(\overline{v}\) = 3439, 3346, 3087, 2192, 1666, 1456, 1363, 1249, 1174 cm−1.

6-Amino-8-(2-hydroxy-3-methoxyphenyl)-3,3-dimethyl-9-nitro-2,3,4,8-tetrahydro-1H-pyrido[1,2-a]pyrimidine-7-carbonitrile (5e, C18H21N5O4)

Yield: 0.293 g (79%); m.p.: 222–224 °C; 1H NMR (300 MHz, acetone-d 6): δ = 11.87 (1H, s, NH), 7.50 (1H, s, OH), 6.78–6.65 (3H, m, ArH), 5.53 (2H, s, NH2), 5.05 (1H, s, CH), 3.78 (3H, s, OMe), 3.71–3.33 (4H, m, 2 CH2N), 1.20 (6H, s, 2 Me) ppm; 13C NMR (75.4 MHz, acetone-d 6): δ = 151.1 (CNN), 150.6 (C–OH), 147.8 (C–OMe), 147.6 (NCNH2), 131.5 (C of Ar), 129.8 (CH of Ar), 121.7 (CH of Ar), 120.0 (CN), 118.4 (CH of Ar), 109.8 (CNO2), 55.5 (CCN), 55.4 (OMe), 53.4, 49.3 (2 CH2N), 36.3 (CH), 27.5 (CMe2), 23.9, 22.8 (2 Me) ppm; IR (KBr): \(\overline{v}\) = 3515, 3344, 3227, 2188, 1623, 1478, 1350, 1223, 1102 cm−1; MS (70 eV): m/z = 371 (M+, 35), 325 (100), 281 (6), 248 (32), 200 (67), 158 (8), 125 (24), 84 (11), 41 (21).

7-Amino-9-(2-hydroxyphenyl)-10-nitro-1,2,3,4,5,9-hexahydropyrido[1,2-a][1, 3]diazepine-8-carbonitrile (5f, C16H17N5O3)

Yield: 0.294 g (90%); m.p.: 236–238 °C; 1H NMR (300 MHz, DMSO-d 6): δ = 10.65 (1H, s, NH), 9.47 (1H, s, OH), 6.98–6.66 (4H, m, ArH), 6.13 (2H, s, NH2), 4.85 (1H, s, CH), 4.05–3.65 (4H, m, 2 CH2NH), 2.05–1.48 (4H, m, 2 CH2) ppm; 13C NMR (75.4 MHz, DMSO-d 6): δ = 158.6 (CNN), 155.6 (C–OH), 154.9 (NCNH2), 129.3 (C of Ar), 129.2 (CH of Ar), 128.1 (CH of Ar), 121.1 (CN), 119.2 (CH of Ar), 115.9 (CH of Ar), 112.6 (CNO2), 64.1 (CCN), 53.3, 45.7 (2 CH2N), 36.9 (CH), 26.8, 25.7 (2 CH2) ppm; IR (KBr): \(\overline{v}\) = 3465, 3358, 3300, 2179, 1645, 1494, 1345, 1211, 1101 cm−1; MS (70 eV): m/z = 327 (M+, 4), 281 (12), 236 (3), 170 (94), 143 (100), 115 (40), 70 (20), 41 (16).

1-Amino-3-(2-hydroxyphenyl)-4-nitro-3,5,5a,6,7,8,9,9a-octahydrobenzo[4,5]imidazo[1,2-a]pyridine-2-carbonitrile (5g, C18H19N5O3)

Mixture of two diasetereoisomers; Yield: 0.275 g (78%); m.p.: 247–249 °C (dec.); IR (KBr): \(\overline{v}\) = 3422, 3330, 3223, 2179, 1654, 1459, 1349, 1227, 1142 cm−1; MS (70 eV): m/z = 353 (M+, 13), 304 (100), 263 (42), 240 (32), 197 (67), 137 (50), 81 (33), 41 (33).

Major isomer (65%): 1H NMR (300 MHz, DMSO-d 6): δ = 9.35 (1H, s, NH), 9.24 (1H, s, OH), 6.98–6.86 (4H, m, ArH), 6.30 (2H, s, NH2), 4.72 (1H, s, CH), 4.49, 4.09 (2H, m, 2 CH), 2.32–1.83 (4H, m, 2 CH2N), 1.74–1.20 (4H, m, 2 CH2) ppm; 13C NMR (75.4 MHz, DMSO-d 6): δ = 155.6 (CNN), 152.2 (C–OH), 148.8 (NCNH2), 130.2 (C of Ar), 130.0 (CH of Ar), 127.7 (CH of Ar), 121.6 (CN), 118.8 (CH of Ar), 115.9 (CH of Ar), 106.2 (CNO2), 63.6 (CCN), 58.7 (OMe), 55.2 (CH2N), 54.7 (CH2NH), 37.9 (CH), 26.1 (CH2), 24.9 (CH2), 21.0 (CH2), 19.7 (CH2) ppm.

Minor isomer (35%): 1H NMR (300 MHz, DMSO-d 6): δ = 9.38 (1H, s, NH), 9.34 (1H, s, OH), 6.73–6.63 (4H, m, ArH), 5.53 (2H, s, NH2), 4.69 (1H, s, CH), 4.46, 4.08 (2H, m, 2 CH), 2.32–1.83 (4H, m, 2 CH2N), 1.74–1.20 (4H, m, 2 CH2) ppm; 13C NMR (75.4 MHz, DMSO-d 6): δ = 155.7 (CNN), 153.9 (C–OH), 151.2 (NCNH2), 130.2 (C of Ar), 130.0 (CH of Ar), 127.9 (CH of Ar), 121.6 (CN), 118.8 (CH of Ar), 115.9 (CH of Ar), 106.2 (CNO2), 66.9 (CCN), 58.7 (OMe), 55.2 (CH2N), 54.7 (CH2NH), 37.9 (CH), 31.0 (CH2), 29.0 (CH2), 24.4 (CH2), 23.3 (CH2) ppm.

1-Amino-3-(2-hydroxy-3-methoxyphenyl)-4-nitro-3,5,5a,6,7,8,9,9a- octahydrobenzo[4,5]imidazo[1,2-a]pyridine-2-carbonitrile (5h, C19H21N5O4)

Yield: 0.306 g (80%); m.p.: 262–264 °C (dec.); 1H NMR (300 MHz, DMSO-d 6): δ = 9.34 (1H, s, NH), 8.45 (1H, s, OH), 6.75 (1H, d, 3 J = 7.8 Hz, Ar), 6.64 (1H, t, 3 J = 7.5 Hz, Ar), 6.53 (1H, d, 3 J = 7.5 Hz, Ar), 6.27 (2H, s, NH2), 4.81 (1H, s, CH), 3.75 (3H, s, OMe), 4.47, 4.05 (2H, m, 2 CH), 2.32–1.83 (4H, m, 2 CH2N), 1.74–1.20 (4H, m, 2 CH2) ppm; 13C NMR (75.4 MHz, DMSO-d 6): δ = 152.1 (CNN), 149.6 (C–OH), 147.9 (C–OMe), 144.4 (NCNH2), 130.9 (C of Ar), 121.7 (CH of Ar), 121.6 (CN), 118.5 (CH of Ar), 110.2 (CH of Ar), 106.5, (CNO2), 59.1 (CCN), 56.1 (OMe), 55.3 (CH2N), 54.7 (CH2NH), 37.1 (CH), 25.9 (CH2), 25.1 (CH2), 21.1 (CH2), 19.6 (CH2) ppm; IR (KBr): \(\overline{v}\) = 3450, 3328, 3223, 2188, 1658, 1469, 1364, 1223, 1132 cm−1; MS (70 eV): m/z = 383 (M+, 3), 336 (64), 293 (18), 239 (13), 200 (100), 173 (10), 137 (55), 81 (33), 41 (20).

6-Amino-8-(2-hydroxy-3-methoxyphenyl)-9-nitro-3,4-dihydro-2H-pyrido[1,2-a] pyrimidine-7-carbonitrile (6i, C16H15N5O4)

Yield: 0.204 g (60%); m.p. >350 °C (dec.); 1H NMR (300 MHz, DMSO-d 6): δ = 8.81 (1H, s, OH) 8.48 (1H, m, ArH), 7.58–7.48 (2H, m, ArH), 7.46 (2H, s, NH2), 3.94 (1H, s, OMe), 3.74–3.55 (4H, m, 2 CH2N), 2.26–1.99 (2H, m, CH2) ppm; 13C NMR (75.4 MHz, DMSO-d 6): δ = 158.9 (CNN), 153.3 (C=C), 150.3 (C–OH), 148.7 (C–OMe), 147.6 (NCNH2), 129.9 (C of Ar), 122.8 (CH of Ar), 122.9 (CH of Ar), 120.9 (CN), 111.7 (CH of Ar), 110.6 (CNO2), 61.5 (CCN), 56.1 (OMe), 46.0, 42.8 (2 CH2N), 20.0 (CH2) ppm; IR (KBr): \(\overline{v}\) = 3453, 3370, 2210, 1609, 1495, 1381, 1210, 1121 cm−1.

6-Amino-8-(2-hydroxy-4-methoxyphenyl)-9-nitro-3,4-dihydro-2H-pyrido[1,2-a] pyrimidine-7-carbonitrile (6j, C16H15N5O4)

Yield: 0.211 g (62%); m.p.: 436–438 °C (dec.); 1H NMR (300 MHz, DMSO-d 6): δ = 8.85 (1H, m, ArH), 7.70–7.50 (2H, m, ArH), 7.13 (2H, s, NH2), 3.91 (3H, s, OMe), 3.85–2.25 (4H, m, CH2N), 2.15–1.13 (2H, m, CH2) ppm; 13C NMR (75.4 MHz, DMSO-d 6): δ = 158.9 (CNN), 153.5 (C=C), 149.1 (C–OH), 148.9 (C–OMe), 147.7 (NCNH2), 130.1 (C of Ar), 120.0 (CN), 113.6 (CH of Ar), 111.9 (CH of Ar), 111.0 (CNO2), 103.2 (CH of Ar), 61.0 (CCN), 55.8 (OMe), 45.9, 42.8 (2 CH2N), 20.4 (CH2) ppm; IR (KBr): \(\overline{v}\) = 3433, 3343, 2207, 1604, 1499, 1374, 1201, 1120 cm−1.

6-Amino-8-(2-hydroxyphenyl)-3,3-dimethyl-9-nitro-3,4-dihydro-2H-pyrido[1,2-a]pyrimidine-7-carbonitrile (6k, C17H17N5O3)

Yield: 0.173 g (51%); m.p.: >350 °C (dec.); 1H NMR (300 MHz, DMSO-d 6): δ = 8.85 (1H, m, ArH), 7.57–7.39 (2H, m, ArH), 7.13 (2H, s, NH2), 2.71–2.25 (4H, m, CH2N), 1.13 (6H, s, 2 Me) ppm; 13C NMR (75.4 MHz, DMSO-d 6): δ = 158.1 (CNN), 153.6 (C=C), 151.0 (C–OH), 148.6 (NCNH2), 130.9 (C of Ar), 129.8 (CH of Ar), 127.8 (CH of Ar), 121.9 (CH of Ar), 120.0 (CN), 115.7 (CH of Ar), 110.8 (CNO2), 61.1 (CCN), 56.9, 50.3 (2 CH2N), 28.1 (CMe2), 24.0, 23.1 (2 Me) ppm.

6-Amino-8-(2-hydroxy-4-methoxyphenyl)-3,3-dimethyl-9-nitro-3,4-dihydro-2H-pyrido[1,2-a]pyrimidine-7-carbonitrile (6l, C18H19N5O4)

Yield: 0.217 g (59%); m.p.: 440–442 °C (dec.); 1H NMR (300 MHz, DMSO-d 6): δ = 8.85 (1H, m, ArH), 7.80–7.39 (2H, m, ArH), 7.13 (2H, s, NH2), 3.91 (3H, s, OMe), 2.71 (2H, m, CH2N), 2.25 (2H, m, CH2NH), 1.13 (6H, s, 2Me) ppm; 13C NMR (75.4 MHz, DMSO-d 6): δ = 158.6 (CNN), 153.9 (C=C), 150.0 (C–OH), 148.9 (C–OMe), 147.8 (NCNH2), 131.3 (C of Ar), 120.6 (CN), 114.0 (CH of Ar), 111.8 (CH of Ar), 110.6 (CNO2), 103.8 (CH of Ar), 59.9 (CCN), 56.8 (OMe), 55.6, 51.0 (2 CH2N), 28.6 (CMe2), 24.1, 23.6 (2 Me) ppm.

7-Amino-9-(2-hydroxy-3-methoxyphenyl)-10-nitro-2,3,4,5-tetrahydropyrido[1,2-a][1,3]diazepine-8-carbonitrile (6m, C17H17N5O4)

Yield: 0.216 g (61%); m.p.: >350 °C (dec.); 1H NMR (300 MHz, DMSO-d 6): δ = 8.49 (1H, m, ArH), 7.70–7.56 (2H, m, ArH), 7.41 (2H, s, NH2), 6.98 (1H, br s, OH), 3.94 (3H, s, OMe), 3.70–3.60 (2H, m, 2 CH2NH), 2.25–1.53 (4H, m, 2 CH2) ppm; 13C NMR (75.4 MHz, DMSO-d 6): δ = 158.9 (CNN), 153.5 (C=C), 149.9 (C–OH), 148.8 (C–OMe), 147.9 (NCNH2), 130.0 (C of Ar), 122.4 (CH of Ar), 121.9 (CH of Ar), 120.6 (CN), 111.4 (CH of Ar), 110.8 (CNO2), 61.9 (CCN), 56.4 (OMe), 53.0, 46.7 (2 CH2N), 26.9, 25.6 (2 CH2) ppm; MS (70 eV): m/z = 355 (M+, 2), 330 (100), 315 (16), 287 (94), 143 (22), 259 (12), 205 (12), 165 (13), 137 (9), 115 (5), 70 (18), 44 (32).

4-[Imidazolidin-2-ylidene(nitro)methyl]-8-methoxy-2-oxo-2H-chromene-3-carbonitrile (7a, C15H12N4O5)

Yield: 0.256 g (78%); m.p.: 392–394 °C; 1H NMR (300 MHz, DMSO-d 6): δ = 9.51 (2H, br s, 2 NH), 8.46 (1H, d, 3 J = 7.8 Hz, Ar), 7.39 (1H, t, 3 J = 7.8 Hz, Ar), 7.34 (1H, d, 3 J = 8.1 Hz, Ar), 4.16–3.82 (4H, m, 2 CH2NH), 3.84 (3H, s, OMe) ppm; 13C NMR (75.4 MHz, DMSO-d 6): δ = 159.9 (CO), 158.2 (CNN), 156.6 (C–OMe), 148.9 (C=C), 148.1, 142.4 (2 C of Ar), 124.7 (CH of Ar), 118.7 (CN), 116.7 (CH of Ar), 116.5 (CH of Ar), 115.7 (CNO2), 80.9 (CCN), 55.6 (OMe), 44.4, 44.0 (2 CH2NH) ppm; IR (KBr): \(\overline{v}\) = 3379, 2209, 1715, 1651, 1496, 1326, 1215, 1104 cm−1; MS (70 eV): m/z = 328 (M+, 2), 309 (100), 266 (24), 238 (18), 203 (14), 182 (8), 155 (14), 114 (11), 77 (26), 44 (50).

4-[Imidazolidin-2-ylidene(nitro)methyl]-2-oxo-2H-chromene-3-carbonitrile (7b, C14H10N4O4)

Yield: 0.211 g (71%); m.p.: 405–407 °C (dec.); 1H NMR (300 MHz, DMSO-d 6): δ = 9.55 (2H, br s, 2 NH), 8.96 (1H, d, 3 J HH = 8.4 Hz, Ar), 7.72 (1H, t, 3 J HH = 6.9 Hz, Ar), 7.48–7.41 (2H, m, Ar), 4.15–3.88 (4H, m, 2 CH2NH) ppm; 13C NMR (75.4 MHz, DMSO-d 6): δ = 158.9 (CO), 157.4 (CNN), 151.9 (C=C), 149.1, 144.4 (2 C of Ar), 125.4 (CH of Ar), 123.7 (CH of Ar), 116.9 (CN), 115.7 (CH of Ar), 115.1 (CNO2), 81.9 (CCN), 44.3, 44.1 (2 CH2NH) ppm; IR (KBr): \(\overline{v}\) = 3347, 2208, 1704, 1653, 1489, 1334, 1208, 1116 cm−1; MS (70 eV): m/z = 298 (M+, 16), 279 (100), 210 (10), 179 (18), 139 (23), 103 (10), 73 (27), 43 (91).

4-[Nitro(tetrahydropyrimidin-2(1H)-ylidene)methyl]-2-oxo-2H-chromene-3-carbonitrile (7c, C15H12N4O4)

Yield: 0.215 g (69%); m.p.: 412–414 °C (dec.); 1H NMR (300 MHz, DMSO-d 6): δ = 10.64, 9.51 (2H, br s, 2 NH), 8.99 (1H, d, 3 J HH = 8.4 Hz, Ar), 7.73 (1H, t, 3 J HH = 8.1 Hz, Ar), 7.45–7.42 (2H, m, Ar), 3.94–3.54 (4H, m, 2 CH2NH), 2.25–1.99 (2H, m, CH2) ppm; 13C NMR (75.4 MHz, DMSO-d 6): δ = 158.6 (CO), 157.4 (CNN), 155.9 (C=C), 150.1, 146.4 (2 C of Ar), 125.4 (CH of Ar), 123.6 (CH of Ar), 116.7 (CN), 115.9 (CH of Ar), 115.0 (CNO2), 81.8 (CCN), 38.5 (2 CH2NH), 19.8 (CH2) ppm; IR (KBr): \(\overline{v}\) = 3937, 2142, 1637, 1422, 1316, 1211, 1150 cm−1; MS (70 eV): m/z = 312 (M+, 0.04), 309 (2), 293 (100), 238 (18), 264 (7), 210 (21), 181 (11), 152 (14), 126 (16), 56 (20).