Sustainable Synthetic Approach for (Pyrazol-4-ylidene)pyridines By Metal Catalyst-Free Aerobic C(sp2)-C(sp3) Coupling Reactions between 1-Amino-2-imino-pyridines and 1-Aryl-5-pyrazolones.

A novel, metal catalyst-free, and efficient method has been developed for the synthesis of (pyrazol-4-ylidene)pyridine derivatives. The process involves dehydrogenative coupling of 1-amino-2-imino-pyridines with 1-aryl-5-pyrazolone derivatives utilizing O2 as the sole oxidant. The new method benefits from a high atom economy, efficiency, and substrate scope, as well as the simplicity of reaction and product purification procedures.

Introduction

In the recent years, cross-declass="Chemical">hydrogenative couclass="Chemical">pling (CDC) reactions have received substantial interest. The major advancements made through studies in this area[1−10] have enabled CDC reactions to become highly attractive class="Chemical">processes for formation of a variety of tyclass="Chemical">pes of bonds. Particularly, interesting is the fact that these oxidative cross-couclass="Chemical">pling class="Chemical">processes can be emclass="Chemical">ployed to form C–C bonds between two C–H comclass="Chemical">ponents in an intermolecular[11−20] or intramolecular[21−24] manner. Moreover, this aclass="Chemical">pclass="Chemical">proach has been extended to the formation of C–N,[25−29] C–O,[30,31] C–S,[32,33] S–N,[34,35] C–P,[36,37] and S–P[38] bonds. Also, CDC reactions have sustainable and green natures including steclass="Chemical">p and atom economy, and they avoid the need for class="Chemical">prefunctionalization of reactants.[39,40] Among the most significant C–C declass="Chemical">pan class="Chemical">hydrogenative cross-coupling reactions are those that bring about bond formation between C(sp2)–H and C(sp3)–H centers. However, processes of this type require activation of the less-reactive C(sp3)–H centers mainly via employment of transition-metal catalysts such as palladium (Pd),[41] copper (Cu),[42] gold (Au),[43] iron (Fe),[46] ruthenium (Ru),[8,47] iridium (Ir),[48] cobalt (Co),[49] and vanadium (V),[50] or nonmetal catalysts like rose bengal,[51] iodine,[33,52] 2,3-dichloro-5,6-dicyano-1,4-benzoquinone,[53] eosin,[54] and phenyliodonium diacetate[55] along with suitable oxidants.

In the study described below, which is a continuation of our research efforts focusing on class="Chemical">pyrazole and class="Chemical">pan class="Chemical">pyridine scaffolds,[44,45] we developed a metal catalyst-free protocol for the C(sp2)–C(sp3) dehydrogenative cross-coupling reactions between 1-amino-2-imino-pyridines and 1-aryl-5-pyrazolones that produce (pyrazol-4-ylidene)pyridine derivatives and utilize O2 as the sole oxidant. One important benefit of the new process is that the reactants are common, pharmaceutically important scaffolds used in the synthesis of pharmacologically active compounds. Moreover, the pyrazole moiety in the products is a common structural component of substances utilized in many areas.[56,57] In particular, the pyrazole moiety is present in many organic compounds that serve as antibacterial,[58−63] antifungal,[64,65] anti-inflammatory,[66,67] antioxidant,[68] anticancer,[69−72] antituberculosis,[73,74] anti-alzheimer,[75] antidiabetic,[76,77] antiviral,[78] antimalarial,[79] antileishmanial,[80] and antiparkinson[81] agents. Moreover, the pyridine group in the products of the new cross-coupling reactions is a common structural feature of a wide range of pharmaceutically and biologically active substances including anticancer, antitumor,[82−84] antiviral,[85] antimicrobial,[86] antidiabetic,[87] antioxidant,[88] anti-inflammatory,[89] and antimalarial[90] agents.

Results and Discussion

Studies aimed at the development of a method for declass="Chemical">hydrogenative cross-couclass="Chemical">pling between the class="Chemical">pan class="Chemical">1-amino-2-imino-pyridine and pyrazolone derivatives commenced by exploring the reaction of 1-amino-2-imino-4-(chlorophenyl)-1,2-dihydropyridine-3-carbonitrile (3a) and 3-methyl-1-phenyl-5-pyrazolone (4a) (Table ). The method used to prepare 3a and related 1-amino-2-imino-pyridine derivatives 3b–f involves a two-step sequence that begins with the preparation of enaminonitriles 2a–f, through reactions of the corresponding ethylidenemalononitriles 1a–f with dimethylformamide dimethylacetal (DMF–DMA) (Scheme ). Enaminonitriles 2a–f were then transformed to the respective targets 3a–f via thermally induced reactions with hydrazine hydrate in ethanol (cf. Scheme ). In the initial effort, we observed that heating a mixture of 3a (3 mmol) and 3-methyl-1-phenyl-5-pyrazolone (4a) (3 mmol) in ethanol (10 mL) at reflux under an air atmosphere for 24 and 48 h leads to complete recovery of the starting materials (Table , entry 1). This process failed to produce products even when carried out in the presence of Pd(OAc)2 (10 mol %) with air or Cu(OAc)2 as oxidants (entries 2,3) and when solvents such as methanol, acetonitrile, propanol, dioxane, toluene, and H2O are employed (entries 4–9). In contrast, reactions of 3a (but not with 4a) did take place to generate the corresponding triazolo[1,5-a]pyridine derivatives 5a and 5b when N,N-dimethylformamide (DMF) or acetic acid was used as solvents. Interestingly, when reaction of 3a with 4a is conducted in ethanol containing 2 equiv acetic acid under an air atmosphere at 130 °C, the (pyrazol-4-ylidene)pyridine 6a is produced in a 38% yield (entry 12).

Table 1

Optimization of Reaction of 1-Aminopyridine 3a and Pyrazolone 4aa

entry	catalyst	solvent	additive (equiv)	oxidant or gas	product (% yield)
1		EtOH		Air
2	Pd(OAc)2	EtOH		air
3	Pd(OAc)2	EtOH		Cu(OAc)2
4	- or Pd(OAc)2	MeOH		air or Cu(OAc)2
5	- or Pd(OAc)2	CH3CN		air or Cu(OAc)2
6	- or Pd(OAc)2	propanol		air or Cu(OAc)2
7	- or Pd(OAc)2	1,4-dioxane		air or Cu(OAc)2
8	- or Pd(OAc)2	toluene		air or Cu(OAc)2
9	- or Pd(OAc)2	water		air or Cu(OAc)2
10	- or Pd(OAc)2	DMF		air	5a (72)
11	- or Pd(OAc)2	AcOH		air	5c (74)
12		EtOH	AcOH(2)	air	6a (38)
13		EtOH	AcOH(4)	air	6a (61)
14		EtOH	AcOH(6)	air	6a (76)
15		EtOH	AcOH(6)	O2	6a (92)
16		EtOH	AcOH(6)	Ar	6a (7)

Reaction conditions: 1-amino-2-imino-pyridine 3a (3 mmol), pyrazolone 4a (3 mmol), in solvent (10 mL), catalyst (10 mol % in case of using Pd(OAc)2), oxidant air, O2 (1 atm) or (2 equiv in case of using Cu(OAc)2), and additive, at 130 °C, for 24 h.

Scheme 1

Preparation of 1-Amino-2-imino-pyridine Derivatives 3a–f

Reaction conditions: class="Chemical">1-amino-2-imino-pyridine 3a (3 mmol), class="Chemical">pan class="Chemical">pyrazolone 4a (3 mmol), in solvent (10 mL), catalyst (10 mol % in case of using Pd(OAc)2), oxidant air, O2 (1 atm) or (2 equiv in case of using Cu(OAc)2), and additive, at 130 °C, for 24 h.

The structure of 6a (Scheme ) was assigned using spectral and X-ray crystallographic data. Mass spectrometric analysis showed that 6a has an exact mass of m/z 416.1147 and a corresponding atomic composition of class="Chemical">C22H17ClN6O. The class="Chemical">pan class="Chemical">1H NMR spectrum of this substance in dimethyl sulfoxide (DMSO) contains a singlet at 6.72 ppm (pyridine H-5), two singlets at 7.36 and 8.64 ppm corresponding to the two NH2 moieties, and a singlet at 2.28 ppm associated with the methyl group. The 1H NMR resonances in the 7.06–8.04 ppm region are associated with the nine aromatic protons in 6a. Moreover, the 13C{1H} NMR spectra of 6a contain the expected 18 signals. Finally, X-ray single-crystallographic analysis of the related (pyrazol-4-ylidene)pyridines 6b and 6k, prepared using the same general method (see below and Figures and 2), enables unambiguous assignment of the structure of this substance. An exploratory study aimed at optimizing the process showed that the quantity of acetic acid has an impact on the efficiency of the process. Specifically, reactions of 3a with 4a in EtOH containing 4 or 6 equiv of HOAc under an air atmosphere at 130 °C were found to form 6a in improved respective yields of 61 and 76% (entries 13,14). Furthermore, when the amount of HOAc exceeds 6 equiv, the process becomes complicated by the formation of increasing quantities of the undesired triazolo[1,5-a]pyridine derivative 5b. Additional studies demonstrated that conducting reaction of 3a with 4a in EtOH containing 6 equiv of HOAc at 130 °C under an oxygen instead of air atmosphere leads to production of 6a in a dramatically high 92% yield (entry 15). Finally, reaction under the same conditions, except using a degassed solvent system and an argon rather than oxygen atmosphere, takes place to form 6a in only 7% yield (entry 16).

Scheme 2

Reactions of 1-Amino-2-imino-pyridine 3a with the Pyrazolone 4a

Figure 1

Plot of X-ray crystallographic data for 6b.

Figure 2

Plot of X-ray crystallographic data for 6k.

Having developed the optimized conditions for the new class="Chemical">(pyrazol-4-ylidene)pyridine forming class="Chemical">process, we next investigated its substrate scoclass="Chemical">pe. For this class="Chemical">purclass="Chemical">pose, we class="Chemical">probed reactions of a diverse range of class="Chemical">pan class="Chemical">1-amino-2-imino-pyridines 3a–f, which are prepared by the sequences shown in Scheme and contain either electron-donating or electron-withdrawing 4-aryl substituents, with several 1,3-disubstituted-pyrazolones 4a–d. The results (Table ) show that the nature of substituents on the aminopyridines and pyrazolones has little effect on the course and efficiency of the dehydrogenative cross-coupling process. Based on the results of 1H NMR and 13C{1H} NMR spectroscopic studies and X-ray single-crystallographic analysis 6b and 6k (Figures and 2), reactions of 3a–f with 4a–c each produce only (Z)-isomers of the 1,2-diamino-6-(pyrazol-4-ylidene)-4-arylpyridine-3-carbonitriles 6a-s in high yields.

Table 2

Acetic Acid-Promoted Dehydrogenative Cross-Coupling Reactions of 1-Amino-2-imino-pyridines 3a–f with Pyrazolones 4a–da

Reaction conditions: 1-amino-2-imino-pyridine 3a–f (3 mmol), pyrazolone 4a–d (3 mmol), in ethanol (10 mL), containing acetic acid (6 equiv), under O2 (1 atm) at 130 °C for 24 h.

Reaction conditions: class="Chemical">1-amino-2-imino-pyridine 3a–f (3 mmol), class="Chemical">pan class="Chemical">pyrazolone 4a–d (3 mmol), in ethanol (10 mL), containing acetic acid (6 equiv), under O2 (1 atm) at 130 °C for 24 h.

A plausible mechanism for the new class="Chemical">(pyrazol-4-ylidene)pyridineclass="Chemical">pan class="Chemical">-forming cross-coupling reaction is displayed in Scheme . In the pathway, HOAc-promoted protonation activates the 1-amino-2-imino-pyridine 3 for C-addition of the enol form of the pyrazolone produced by HOAc-induced enolization. The adduct A, generated in this manner, then undergoes dehydrogenation through reaction with molecular oxygen to form the (pyrazol-4-ylidene)pyridine 6 product.

Scheme 3

Plausible Mechanism for Formation of (Pyrazol-4-ylidene)pyridines 6 in HOAc-Promoted Dehydrogenative Cross-Coupling Reactions of 1-Amino-2-imino-pyridines 3 with Pyrazolones 4

Finally, the utility of this CDC coupling on a laboratory preparative scale has been probed. We observed that a gram scale (10 mmol) reaction of 3a with 4a under the optimal conditions produces 6a in 90% isolated yield (Scheme ).

Scheme 4

Gram Scale Synthesis of 6a

Conclusions

In summary, in the effort discussed above, we conducted an efficient class="Chemical">metal catalystclass="Chemical">pan class="Chemical">-free aerobic dehydrogenative cross-coupling reaction between the 1-amino-2-imino-pyridines and 1-aryl-5-pyrazolones, which generates (pyrazol-4-ylidene)pyridines. The process has a high functional group tolerance and atom economy, and it employs simple, environmentally compatible reaction and purification procedures. As such, the protocol should find future applications to the synthesis of these N-heterocycles of pharmaceutical and agricultural interest.

Experimental Section

General

Melting points were recorded on a Griffin melting point apparatus and are uncorrected. IR spectra were recorded using KBr disks using a Jasco FT-IR-6300 spectrophotometer. class="Chemical">1H NMR (400 MHz) or (600 MHz) and class="Chemical">pan class="Chemical">13C{1H} NMR (100 MHz) or (150 MHz) spectra were recorded at 25 °C using DMSO-d6 as a solvent with TMS as the internal standard on a Bruker DPX 400 or 600 super-conducting NMR spectrometer. Chemical shifts (δ) are reported in ppm. Low-resolution electron impact mass spectra [MS (EI)] and high-resolution electron impact mass spectra [HRMS (EI)] were performed using a high-resolution GC–MS (DFS) thermo spectrometer at 70.1 eV and a magnetic sector mass analyzer. Following that, the courses of reactions and checking homogeneity of products were performed using thin-layer chromatography. The X-ray crystallographic data were collected by using a Rigaku R-AXIS RAPID diffractometer and Bruker X8 Prospector at room temperature by using Cu Kα radiation. The structures were solved by using direct methods and expanded using Fourier techniques. The nonhydrogen atoms were refined anisotropically. The structures were solved and refined using the Bruker SHELXTL Software Package (Structure solution program- SHELXS-97 and Refinement program- SHELXL-97).[91] Data were corrected for the absorption effects using the multiscan method (SADABS). The arylethylidenemalononitriles 1a–f(92) and enaminonitriles 2a–f(93) were prepared according to literature procedures.

General Procedure for the Preparation of 1-Amino-2-imino-4-aryl-1,2-dihydropyridine-3-carbonitrile 3a–f(44b)

A mixture of the class="Chemical">enaminonitrile 2 (20 mmol) and class="Chemical">pan class="Chemical">hydrazine hydrate (1.5 mL, 30 mmol) in 60 mL of ethanol was stirred at reflux for 1 h. The mixture was concentrated in vacuo giving a solid that was crystallized from the appropriate solvent to give 3 as the pure product.

1-Amino-4-(4-chlorophenyl)-2-imino-1,2-dihydropyridine-3-carbonitrile (3a)

It is obtained as bright yellow crystals; yield: 4.35 g (89%); mp 234–235 °C, IR (KBr) ν/cm–1: 3314, 3267 (NH2), 3178 (NH), 2210 (CN); class="Chemical">1H NMR (400 MHz, class="Chemical">pan class="Chemical">DMSO-d6): δ 5.89 (d, J = 6.8 Hz, 1H), 6.16 (s, 2H), 6.61 (brs, 1H), 7.61–7.63 (m, 4H), 7.81 (d, J = 6.8 Hz, 1H); 13C{1H} NMR (100 MHz, DMSO-d6): δ 101.3, 116.8, 128.8, 129.7, 134.8, 135.0, 143.1153.9, 154.3; MS (EI) m/z: (%) 246 (M+ + 2, 34.29), 245 (M+ + 1, 17.94), 244 (M+, 100); HRMS (EI) m/z: calcd for C12H9N4Cl(M+) 244.0510; found, 244.0510.

1-Amino-4-(4-bromophenyl)-2-imino-1,2-dihydropyridine-3-carbonitrile (3b)

It is obtained as yellow crystals; yield: 5.3 g (92%); mp 239–240 °C, IR (KBr) ν/cm–1: 3311, 3263 (NH2), 3176 (NH), 2208 (CN); class="Chemical">1H NMR (400 MHz, class="Chemical">pan class="Chemical">DMSO-d6): δ 5.90 (d, J = 6.8 Hz, 1H), 6.17 (s, 2H), 6.73 (brs, 1H), 7.54 (d, J = 8.4 Hz, 2H), 7.74 (d, J = 8.4 Hz, 2H), 7.82 (d, J = 6.8 Hz, 1H); 13C{1H} NMR (100 MHz, DMSO-d6): δ 102.2, 116.6, 123.7, 130.0, 131.8, 135.3, 143.4, 143.4, 154.2, 154.3; MS (EI) m/z: (%) 290 (M+ + 2, 97.06), 289 (M+ + 1, 18.49), 288 (M+, 100); HRMS (EI) m/z: calcd for C12H9N4Br(M+) 288.0005; found, 288.0005.

1-Amino-4-(4-fluorophenyl)-2-imino-1,2-dihydropyridine-3-carbonitrile (3c)

It is obtained as yellow crystals; yield: 4.35 g (89%); mp 200–201 °C, IR (KBr) ν/cm–1: 3312, 3258 (NH2), 3175 (NH), 2209 (CN); class="Chemical">1H NMR (600 MHz, class="Chemical">pan class="Chemical">DMSO-d6): δ 5.89 (d, J = 7.2 Hz, 1H), 6.11 (s, 2H), 6.63 (brs, 1H), 7.33–7.36 (m, 2H), 7.63–7.65 (m, 2H), 7.78 (d, J = 7.2 Hz, 1H); 13C{1H} NMR (150 MHz, DMSO-d6): δ 101.3, (115.47, 115.62) (d, 2JCF = 22.5 Hz), 116.7, (129.97, 130.03) (d, 3JCF = 9.0 Hz), 132.47, 132.49, 142.7, 153.8, 154.3, (162.01, 163.65) (d, 1JCF = 246 Hz); MS (EI) m/z: (%) 229 (M+ + 1, 28.75), 228 (M+, 100); HRMS (EI) m/z: calcd for C12H9N4F(M+) 228.0806; found, 228.0806.

1-Amino-2-imino-4-(4-nitrophenyl)-1,2-dihydropyridine-3-carbonitrile (3d)

It is obtained as yellow crystals; yield: 4.4 g (87%); mp 207–208 °C, IR (KBr) ν/cm–1: 3312, 3255 (NH2), 3161 (NH), 2206 (CN); class="Chemical">1H NMR (400 MHz, class="Chemical">pan class="Chemical">DMSO-d6): δ 5.94 (d, J = 7.2 Hz, 1H), 6.23 (brs, 2H), 6.74 (brs, 1H), 7.85–7.87 (m, 3H), 8.36 (d, J = 7.6 Hz, 2H); 13C{1H} NMR (100 MHz, DMSO-d6): δ 97.7, 101.3, 116.5, 123.9, 129.5, 142.5, 143.6, 148.2, 153.1, 154.0; MS (EI) m/z: (%) 256 (M+ + 1, 17.92), 255 (M+, 100); HRMS (EI) m/z: calcd for C12H9N5O2(M+) 255.0751; found, 255.0750.

1-Amino-2-imino-4-phenyl-1,2-dihydropyridine-3-carbonitrile (3e)

It is obtained as yellow crystals; yield: 3.7 g (89%); mp 165–166 °C, IR (KBr) ν/cm–1: 3318, 3226 (NH2), 3137 (NH), 2211 (CN); class="Chemical">1H NMR (400 MHz, class="Chemical">pan class="Chemical">DMSO-d6): δ 5.90 (d, J = 7.2 Hz, 1H), 6.16 (s, 2H), 6.53 (brs, 1H), 7.52–7.59 (m, 5H), 7.81 (d, J = 7.2 Hz, 1H); 13C{1H} NMR (100 MHz, DMSO-d6): δ 97.2, 101.6, 117.1, 127.8, 128.8, 130.1, 136.3, 143.1, 154.6, 155.1; MS (EI) m/z (%) 211 (M+ + 1, 18.25), 210 (M+, 100); HRMS (EI) m/z calcd for C12H10N4 (M+) 210.0899; found, 210.0899.

1-Amino-2-imino-4-p-tolyl-1,2-dihydropyridine-3-carbonitrile (3f)

It is obtained as yellow crystals; yield: 4.3 g (90%); mp 223–224 °C, IR (KBr) ν/cm–1: 3315, 3262 (NH2), 3171 (NH), 2207 (CN); class="Chemical">1H NMR (400 MHz, class="Chemical">pan class="Chemical">DMSO-d6): δ 2.38 (s, 3H), 5.88 (d, J = 7.2 Hz, 1H), 6.13 (s, 2H), 6.58 (brs, 1H), 7.34 (d, J = 8.0 Hz, 2H), 7.48 (d, J = 8.0 Hz, 2H), 7.79 (d, J = 7.2 Hz, 1H); 13C{1H} NMR (100 MHz, DMSO-d6): δ 20.9, 101.6, 117.2, 127.7, 129.3, 133.3, 140.0, 142.6, 143.0, 154.6, 155.0; MS (EI) m/z (%) 225 (M+ + 1, 13.19), 224 (M+, 72.89); HRMS (EI) m/z calcd for C13H12N4 (M+) 224.1056; found, 224.1055.

7-(4-Chlorophenyl)[1,2,4]triazolo[1,5-a]pyridine-8-carbonitrile (5a)

It is recrystallized from the class="Chemical">EtOH/class="Chemical">pan class="Chemical">dioxane mixture (3:1) as yellow crystals; yield: 0.55 g (72%), mp above 300 °C; IR (KBr) ν/cm–1: 2226 (CN); 1H NMR (600 MHz, DMSO-d6): δ 7.48 (d, J = 7.2 Hz, 1H), 7.70 (d, J = 8.4 Hz, 2H), 7.80 (d, J = 8.4 Hz, 2H), 8.75 (s, 1H), 9.35 (d, J = 7.2 Hz, 1H); 13C{1H} NMR (150 MHz, DMSO-d6): δ 97.8, 114.4, 115.4, 129.1, 130.8, 133.2, 134.2, 135.3, 148.3, 149.6, 155.5; MS (EI) m/z (%) 256 (M+ + 2, 33.19), 255 (M+ + 1, 16.29), 254 (M+, 100). HRMS (EI) m/z calcd for C13H7ClN4 (M+) 254.1147; found, 254.1147.

7-(4-Chlorophenyl)-2-methyl[1,2,4]triazolo[1,5-a]pyridine-8-carbonitrile (5b)

It is recrystallized from the class="Chemical">EtOH/class="Chemical">pan class="Chemical">dioxane mixture (3:1) as buff crystals; yield: 0.6 g (74%), mp 225–226 °C; IR (KBr) ν/cm–1: 2223 (CN); 1H NMR (600 MHz, DMSO-d6): δ 2.54 (s, 3H), 7.36 (d, J = 6.8 Hz, 1H), 7.67 (d, J = 8.4 Hz, 2H), 7.76 (d, J = 8.4 Hz, 2H), 9.20 (d, J = 6.8 Hz, 1H); 13C{1H} NMR (150 MHz, DMSO-d6): δ 14.1, 96.6, 114.5, 128.7, 129.1, 130.7, 132.6, 134.3, 135.2, 147.8, 150.2, 165.1; MS (EI): m/z (%) 270 (M+ + 2, 29.65), 269 (M+ + 1, 14.89), 268 (M+, 100). HRMS (EI): m/z calcd for C14H10ClN4 (M+) 268.1147; found, 268.1147.

General Procedure for the Preparation of (Pyrazol-4-ylidene)pyridines Derivatives 6a–s

A mixture of the class="Chemical">1-amino-2-imino-pyridine 3 (3 mmol) and class="Chemical">pan class="Chemical">pyrazolone derivative 4 (3 mmol) in ethanol (10 mL) containing acetic acid (6 equiv) under O2 (1 atm) was stirred at 130 °C for 24 h. The mixture was then cooled to room temperature. The formed solid was collected by filtration and recrystallized from the appropriate solvent (see below) to give the (pyrazol-4-ylidene)pyridine 6.

(Z)-1,2-Diamino-4-(4-chlorophenyl)-6-(3-methyl-5-oxo-1-phenyl-1H-pyrazol-4(5H)-ylidene)-1,6-dihydropyridine-3-carbonitrile (6a)

It is recrystallized from the class="Chemical">EtOH/class="Chemical">pan class="Chemical">dioxane mixture (1:2) as deep orange crystals; yield: 1.15 g (92%), mp above 300 °C; IR (KBr) ν/cm–1: 3338, 3298, 3262, 3237 (2NH2), 2213 (CN), 1659 (CO); 1H NMR (600 MHz, DMSO-d6): δ 2.28 (s, 3H), 6.72 (s, 1H), 7.08 (t, J = 7.8 Hz, 1H), 7.34–7.36 (m, 4H), 7.66 (d, J = 8.4 Hz, 2H), 7.71 (d, J = 8.4 Hz, 2H), 8.03 (d, J = 7.8 Hz, 2H), 8.64 (s, 2H); 13C{1H} NMR (150 MHz, DMSO-d6): δ 15.7, 82.7, 96.2, 110.5, 115.3, 118.3, 123.2, 128.4, 128.9, 130.2, 134.5, 135,3, 140.0, 146.6, 151.8, 153.8, 157.3, 162.4; MS (EI): m/z (%) 417 (M+ + 1, 34.78), 416 (M+, 100). HRMS (EI): m/z calcd for C22H17ClN6O (M+) 416.1147; found, 416.1147.

(Z)-1,2-Diamino-4-(4-bromophenyl)-6-(3-methyl-5-oxo-1-phenyl-1H-pyrazol-4(5H)-ylidene)-1,6-dihydropyridine-3-carbonitrile (6b)

It is recrystallized from the class="Chemical">EtOH/class="Chemical">pan class="Chemical">dioxane mixture (1:1) or from aqueous DMSO for the X-ray single crystal as orange crystals; yield: 1.3 g (94%), mp 296–297 °C; IR (KBr) ν/cm–1: 3371, 3316, 3244, 3102 (2NH2), 2216 (CN), 1664 (CO); 1H NMR (600 MHz, DMSO-d6): δ 2.29 (s, 3H), 6.73 (s, 1H), 7.09 (t, J = 7.8 Hz, 1H), 7.35–7.37 (m, 4H), 7.64 (d, J = 7.8 Hz, 2H), 7.80 (d, J = 7.8 Hz, 2H), 8.04 (d, J = 7.8 Hz, 2H), 8.65 (s, 2H); 13C{1H} NMR (150 MHz, DMSO-d6): δ 15.7, 82.6, 96.2, 110.4, 115.3, 118.3, 123.2, 124.1, 128.4, 130.4, 131.9, 134.9, 140.0, 146.6, 151.8, 153.8, 157.3, 162.4; MS (EI): m/z (%) 462 (M+ + 2, 100), 461 (M+ + 1, 27.15), 460 (M+, 97.98). HRMS (EI): m/z calcd for C22H17BrN6O (M+) 460.0642; found, 460.0643. Crystal Data, moiety formula: 2(C22H17BrN6O), H2O, M = 940.65, monoclinic, a = 17.61(2) Å, b = 7.593(6) Å, c = 15.88(2) Å, V = 2007(3) Å3, α = γ = 90°, β = 109.057(9)°, space group: P2/c (#13), Z = 2, Dcalc = 1.556 g·cm–3, no. of reflection measured 3482, 2θmax = 50.1°, R1 = 0.0694 (CCDC 1889196).[95]

(Z)-1,2-Diamino-4-(4-fluorophenyl)-6-(3-methyl-5-oxo-1-phenyl-1H-pyrazol-4(5H)-ylidene)-1,6-dihydropyridine-3-carbonitrile (6c)

It is recrystallized from the class="Chemical">EtOH/class="Chemical">pan class="Chemical">dioxane mixture (1:1) as deep orange crystals; yield: 1.05 g (88%), mp above 300 °C; IR (KBr) ν/cm–1: 3325, 3284, 3231, 3145 (2NH2), 2215 (CN), 1661 (CO); 1H NMR (600 MHz, DMSO-d6): δ 2.28 (s, 3H), 6.72 (s, 1H), 7.08 (t, J = 7.2 Hz, 1H), 7.34–7.37 (m, 4H), 7.42 (t, J = 7.2 Hz, 2H), 7.75–7.77 (m, 2H), 8.04 (d, J = 7.2 Hz, 2H), 8.63 (s, 2H); 13C{1H} NMR (150 MHz, DMSO-d6): δ 15.7, 82.8, 96.1, 110.6, 115.4, (115.87, 116.01) (d, 2JCF = 21.0 Hz), 118.3, 123.2, 128.5, (130.80, 130.86) (d, 3JCF = 9.0 Hz), 132.1, 140.0, 146.6, 152.0, 153.7, 157.3, 162.4, (162.48, 164.12) (d, 1JCF = 246 Hz); MS (EI): m/z (%) 401 (M+ + 1, 3.97), 400 (M+, 13.05), 385 (M+ – 15, 100). HRMS (EI): m/z calcd for C22H17FN6O (M+) 400.1442; found, 400.1442.

(Z)-1,2-Diamino-6-(3-methyl-5-oxo-1-phenyl-1H-pyrazol-4(5H)-ylidene)-4-(4-nitrophenyl)-1,6-dihydropyridine-3-carbonitrile (6d)

It is recrystallized from the class="Chemical">EtOH/class="Chemical">pan class="Chemical">dioxane mixture (1:1) as orange crystals; yield: 1.14 g (89%), mp above 300 °C; IR (KBr) ν/cm–1: 3449, 3370, 3278, 3215 (2NH2), 2212 (CN), 1638 (CO); 1H NMR (600 MHz, DMSO-d6): δ 2.29 (s, 3H), 6.78 (s, 1H), 7.08 (t, J = 7.8 Hz, 1H), 7.35–7.37 (m, 4H), 7.96 (d, J = 9.0 Hz, 2H), 8.03 (d, J = 7.8 Hz, 2H), 8.40 (d, J = 9.0 Hz, 2H), 8.72 (s, 2H); 13C{1H} NMR (150 MHz, DMSO-d6): δ 15.7, 82.6, 96.5, 110.6, 115.1, 118.3, 123.2, 123.9, 128.5, 130.0, 139.9, 142.0, 146.7, 148.4, 150.8, 153.9, 157.2, 162.4; MS (EI): m/z (%) 428 (M+ + 1, 27.85), 427 (M+, 100). HRMS (EI): m/z calcd for C22H17N7O3 (M+) 427.1387; found, 427.1387.

(Z)-1,2-Diamino-6-(3-methyl-5-oxo-1-phenyl-1H-pyrazol-4(5H)-ylidene)-4-phenyl-1,6-dihydropyridine-3-carbonitrile (6e)

It is recrystallized from the class="Chemical">EtOH/class="Chemical">pan class="Chemical">dioxane mixture (3:1) as orange crystals; yield: 0.90 g (79%), mp 252–253 °C; IR (KBr) ν/cm–1: 3354, 3291, 3249, 3198 (2NH2), 2214 (CN), 1661 (CO); 1H NMR (600 MHz, DMSO-d6): δ 2.29 (s, 3H), 6.72 (s, 1H), 7.07 (t, J = 7.8 Hz, 1H), 7.34–7.36 (m, 4H), 7.51–7.68 (m, 5H), 8.05 (d, J = 7.8 Hz, 2H), 8.59 (s, 2H); 13C{1H} NMR (150 MHz, DMSO-d6): δ 15.7, 82.8, 96.0, 110.5, 115.4, 118.3, 123.1, 128.2, 128.9, 130.4, 132.9, 135.7, 140.0, 146.6, 153.1, 153.7, 157.3, 162.4; MS (EI): m/z (%) 383 (M+ + 1, 41.89), 382 (M+, 94.08), 367 (M+ – 15, 100). HRMS (EI): m/z calcd for C22H18N6O (M+) 382.1537; found, 382.1536.

(Z)-1,2-Diamino-4-(4-chlorophenyl)-6-(3-methyl-5-oxo-1-p-tolyl-1H-pyrazol-4(5H)-ylidene)-1,6-dihydropyridine-3-carbonitrile (6f)

It is recrystallized from the class="Chemical">EtOH/class="Chemical">pan class="Chemical">dioxane mixture (1:2) as orange crystals; yield: 1.08 g (83%), mp 294–295 °C; IR (KBr) ν/cm–1: 3417, 3365, 3308, 3242 (2NH2), 2217 (CN), 1654 (CO); 1H NMR (600 MHz, DMSO-d6): δ 2.26 (s, 3H), 2.28 (s, 3H), 6.70 (s, 1H), 7.15 (d, J = 8.4 Hz, 2H), 7.38 (s, 2H), 7.65 (d, J = 9.0 Hz, 2H), 7.70 (d, J = 9.0 Hz, 2H), 7.89 (d, J = 8.4 Hz, 2H), 8.64 (s, 2H); 13C{1H} NMR (150 MHz, DMSO-d6): δ 15.7, 20.5, 82.5, 96.2, 110.4, 115.3, 118.3, 128.8, 128.9, 130.2, 132.0, 134.5, 135.3, 137.7, 146.3, 151.6, 153.7, 157.3, 162.2; MS (EI): m/z (%) 432 (M+ + 2, 32.18), 431 (M+ + 1, 28.89), 430 (M+, 100). HRMS (EI): m/z calcd for C23H19ClN6O (M+) 430.1303; found, 430.1302.

(Z)-1,2-Diamino-4-(4-bromophenyl)-6-(3-methyl-5-oxo-1-p-tolyl-1H-pyrazol-4(5H)-ylidene)-1,6-dihydropyridine-3-carbonitrile (6g)

It is recrystallized from the class="Chemical">EtOH/class="Chemical">pan class="Chemical">dioxane mixture (1:2) as orange crystals; yield: 1.22 g (86%), mp 299–300 °C; IR (KBr) ν/cm–1: 3370, 3295, 3210, 3104 (2NH2), 2216 (CN), 1661 (CO); 1H NMR (600 MHz, DMSO-d6): δ 2.26 (s, 3H), 2.28 (s, 3H), 6.70 (s, 1H), 7.15 (d, J = 8.4 Hz, 2H), 7.37 (s, 2H), 7.62 (d, J = 8.4 Hz, 2H), 7.78 (d, J = 8.4 Hz, 2H), 7.88 (d, J = 8.4 Hz, 2H), 8.62 (s, 2H); 13C{1H} NMR (150 MHz, DMSO-d6): δ 15.7, 20.5, 82.5, 96.3, 110.4, 115.4, 118.3, 124.1, 128.9, 130.4, 131.9, 132.1, 134.9, 137.7, 146.3, 151.7, 153.8, 157.3, 162.2; MS (EI): m/z (%) 476 (M+ + 2, 42.39), 475 (M+ + 1, 12.75), 474 (M+, 43.18), 461 (100). HRMS (EI): m/z calcd for C23H19BrN6O (M+) 474.0798; found, 474.0798.

(Z)-1,2-Diamino-4-(fluorophenyl)-6-(3-methyl-5-oxo-1-p-tolyl-1H-pyrazol-4(5H)-ylidene)-1,6-dihydropyridine-3-carbonitrile (6h)

It is recrystallized from the class="Chemical">EtOH/class="Chemical">pan class="Chemical">dioxane mixture (1:1) as orange crystals; yield: 0.98 g (79%), mp 280–281 °C; IR (KBr) ν/cm–1: 3365, 3280, 3228, 3115 (2NH2), 2214 (CN), 1658 cm–1 (CO); 1H NMR (600 MHz, DMSO-d6): δ 2.27 (s, 3H), 2.29 (s, 3H), 6.71 (s, 1H), 7.15 (d, J = 7.8 Hz, 2H), 7.26 (d, J = 8.4 Hz, 2H), 7.37 (s, 2H), 7.64 (d, J = 8.4 Hz, 2H), 7.89 (d, J = 7.8 Hz, 2H), 8.61 (s, 2H); 13C{1H} NMR (150 MHz, DMSO-d6): δ 15.7, 20.5, 82.5, 96.2, 110.5, 115.4, (115.93, 116.09) (d, 2JCF = 24.0 Hz), 118.3, 123.9, 128.7, (130.56, 130.64) (d, 3JCF = 12.0 Hz), 132.0, 139.0, 145.9, 151.9, 153.8, 157.3, 162.2, (162.55, 164.21) (d, 1JCF = 249 Hz); MS (EI): m/z (%) 415 (M+ + 1, 16.88), 414 (M+, 60.97), 399 (M+ – 15, 100). HRMS (EI): m/z calcd for C23H19FN6O (M+) 414.1599; found, 414.1598.

(Z)-1,2-Diamino-6-(3-methyl-5-oxo-1-p-tolyl-1H-pyrazol-4(5H)-ylidene)-4-(4-nitrophenyl)-1,6-dihydropyridine-3-carbonitrile (6i)

It is recrystallized from the class="Chemical">EtOH/class="Chemical">pan class="Chemical">dioxane mixture (2:1) as reddish brown crystals; yield: 0.97 g (74%), mp 272–273 °C; IR (KBr) ν/cm–1: 3422, 3358, 3287, 3206 (2NH2), 2216 (CN), 1657 (CO); 1H NMR (600 MHz, DMSO-d6): δ 2.27 (s, 3H), 2.28 (s, 3H), 6.77 (s, 1H), 7.16 (d, J = 8.4 Hz, 2H), 7.38 (s, 2H), 7.89 (d, J = 8.4 Hz, 2H), 7.95 (d, J = 8.4 Hz, 2H), 8.40 (d, J = 8.4 Hz, 2H), 8.70 (s, 2H); 13C{1H} NMR (150 MHz, DMSO-d6): δ 15.7, 20.4, 82.3, 96.5, 110.6, 115.1, 118.3, 123.9, 128.8, 129.9, 132.1, 137.6, 142.0, 146.3, 148.4, 150.6, 153.9, 157.2, 162.2; MS (EI): m/z (%) 442 (M+ + 1, 15.62), 441 (M+, 56.18), 426 (M+ – 15, 100). HRMS (EI): m/z calcd for C23H19N7O3 (M+) 441.1544; found, 441.1545.

(Z)-1,2-Diamino-6-(3-methyl-5-oxo-1-p-tolyl-1H-pyrazol-4(5H)-ylidene)-4-phenyl-1,6-dihydropyridine-3-carbonitrile (6j)

It is recrystallized from the class="Chemical">EtOH/class="Chemical">pan class="Chemical">dioxane mixture (1:1) as orange crystals; yield: 0.95 g (81%), mp 286–287 °C; IR (KBr) ν/cm–1: 3408, 3345, 3289, 3133 (2NH2), 2220 (CN), 1655 (CO); 1H NMR (600 MHz, DMSO-d6): δ 2.27 (s, 3H), 2.28 (s, 3H), 6.71 (s, 1H), 7.15 (d, J = 8.4 Hz, 2H), 7.38 (s, 2H), 7.58–7.59 (m, 3H), 7.68–7.69 (m, 2H), 7.90 (d, J = 8.4 Hz, 2H), 8.60 (s, 2H); 13C{1H} NMR (150 MHz, DMSO-d6): δ 15.7, 20.5, 82.6, 96.1, 110.5, 115.5, 118.3, 128.2, 128.8, 128.9, 130.4, 132.0, 135.7, 137.7, 146.2, 152.9, 153.7, 157.4, 162.2; MS (EI): m/z (%) 397 (M+ + 1, 14.08), 396 (M+, 51.14). HRMS (EI): m/z calcd for C23H20N6O (M+) 396.1693; found, 396.1694.

(Z)-1,2-Diamino-6-(3-methyl-5-oxo-1-p-tolyl-1H-pyrazol-4(5H)-ylidene)-4-p-tolyl-1,6-dihydropyridine-3-carbonitrile (6k)

It is recrystallized from the MeOH/class="Chemical">dioxane mixture (1:2) as orange crystals; yield: 0.92 g (75%), mclass="Chemical">p above 300 °C; IR (KBr) ν/cm–1: 3378, 3328, 3260, 3172 (2NH2), 2213 (CN), 1641 (CO); class="Chemical">pan class="Chemical">1H NMR (600 MHz, DMSO-d6): δ 2.27 (s, 3H), 2.28 (s, 3H), 2.40 (s, 3H), 6.68 (s, 1H), 7.15 (d, J = 8.4 Hz, 2H), 7.37 (s, 2H), 7.39 (d, J = 8.4 Hz, 2H), 7.58 (d, J = 8.4 Hz, 2H), 7.90 (d, J = 8.4 Hz, 2H),8.56 (s, 2H); 13C{1H} NMR (150 MHz, DMSO-d6): δ 15.7, 20.4, 20.9, 82.5, 96.0, 110.3, 115.6, 118.3, 128.2, 128.8, 129.5, 132.0, 132.9, 137.7, 140.4, 146.2, 153.0, 157.4, 162.2; MS (EI): m/z (%) 411 (M+ + 1, 9.05), 410 (M+, 31.22), 395 (M+ – 15, 100). HRMS (EI): m/z calcd for C24H22N6O (M+) 410.1850; found, 410.1849. Crystal Data, moiety formula: C24H22N6O, M = 410.48, monoclinic, a = 24.0794(10) Å, b = 4.5338(2) Å, c = 19.1155(7) Å, V = 2085.15(15) Å3, α = γ = 90°, β = 92.320(3)°, space group: P21/c, Z = 4, Dcalc = 1.308 g·cm–3, no. of reflection measured 3640, θmax = 66.333°, R1 = 0.0565 (CCDC 1889196).[95]

(Z)-1,2-Diamino-4-(4-chlorophenyl)-6-[1-(4-chlorophenyl)-3-methyl-5-oxo-1H-pyrazol-4(5H)-ylidene]-1,6-dihydropyridine-3-carbonitrile (6l)

It is recrystallized from the class="Chemical">EtOH/class="Chemical">pan class="Chemical">dioxane mixture (1:2) as deep orange crystals; yield: 1.20 g (89%), mp above 300 °C; IR (KBr) ν/cm–1: 3399, 3298, 3185, 3092 (2NH2), 2217 (CN), 1665 (CO); 1H NMR (600 MHz, DMSO-d6): δ 2.27 (s, 3H), 6.72 (s, 1H), 7.31 (s, 2H), 7.40 (d, J = 8.4 Hz, 2H), 7.60 (d, J = 7.8 Hz, 2H), 7.70 (d, J = 7.8 Hz, 2H), 8.08 (d, J = 8.4 Hz, 2H), 8.67 (s, 2H); 13C{1H} NMR (150 MHz, DMSO-d6): δ 15.6, 83.1, 96.0, 110.6, 115.2, 119.5, 126.8, 128.4, 128.9, 130.2, 134.4, 135,4, 138.9, 147.2, 152.0, 153.7, 157.3, 162.4; MS (EI): m/z (%) 452 (M+ + 2, 61.23), 451 (M+ + 1, 24.98), 450 (M+, 100). HRMS (EI): m/z calcd for C22H16Cl2N6O (M+) 450.0757; found, 450.0757.

(Z)-1,2-Diamino-4-(4-bromophenyl)-6-[1-(4-chlorophenyl)-3-methyl-5-oxo-1H-pyrazol-4(5H)-ylidene]-1,6-dihydropyridine-3-carbonitrile (6m)

It is recrystallized from the class="Chemical">EtOH/class="Chemical">pan class="Chemical">dioxane mixture (1:3) as deep orange crystals; yield: 1.38 g (93%), mp above 300 °C; IR (KBr) ν/cm–1: 3398, 3295, 3180, 3093 (2NH2), 2218 (CN), 1664 (CO); 1H NMR (600 MHz, DMSO-d6): δ 2.27 (s, 3H), 6.72 (s, 1H), 7.31 (s, 2H), 7.40 (d, J = 7.8 Hz, 2H), 7.63 (d, J = 7.8 Hz, 2H), 7.78 (d, J = 7.8 Hz, 2H), 8.09 (d, J = 7.8 Hz, 2H), 8.66 (s, 2H); 13C{1H} NMR (150 MHz, DMSO-d6): δ 15.6, 83.0, 96.0, 110.5, 115.2, 119.4, 124.1, 126.8, 128.4, 130.4, 131.9, 134.8, 138.9, 147.2, 152.1, 153.7, 157.2, 162.4; MS (EI): m/z (%) 496 (M+ + 2, 100), 495 (M+ + 1, 21.13), 494 (M+, 75.04). HRMS (EI): m/z calcd for C22H16BrClN6O (M+) 494.0252; found, 494.0251.

(Z)-1,2-Diamino-6-[1-(4-chlorophenyl)-3-methyl-5-oxo-1H-pyrazol-4(5H)-ylidene]-4-(4-fluorophenyl)-1,6-dihydropyridine-3-carbonitrile (6n)

It is recrystallized from the class="Chemical">EtOH/class="Chemical">pan class="Chemical">dioxane mixture (1:2) as deep orange crystals; yield: 1.10 g (85%), mp above 300 °C; IR (KBr) ν/cm–1: 3394, 3293, 3190, 3111 (2NH2), 2220 (CN), 1658 (CO); 1H NMR (600 MHz, DMSO-d6): δ 2.28 (s, 3H), 6.72 (s, 1H), 7.31 (s, 2H), 7.40–7.44 (m, 4H), 7.74–7.77 (m, 2H), 8.09 (d, J = 8.4 Hz, 2H), 8.64 (s, 2H); 13C{1H} NMR (150 MHz, DMSO-d6): δ 15.6, 83.3, 95.9, 110.6, 115.4, (115.87, 116.02) (d, 2JCF = 22.5 Hz), 119.5, 126.8, 128.4, (130.82, 130.88) (d, 3JCF = 9.0 Hz), 132.1, 138.9, 147.2, 152.2, 153.6, 157.3, 162.4, (162.50, 164.14) (d, 1JCF = 246 Hz); MS (EI): m/z (%) 435 (M+ + 1, 5.83), 434 (M+, 20.78), 419 (M+ – 15, 100). HRMS (EI): m/z calcd for C22H16ClFN6O (M+) 434.1053; found, 434.1053.

(Z)-1,2-Diamino-6-[1-(4-chlorophenyl)-3-methyl-5-oxo-1H-pyrazol-4(5H)-ylidene]-4-(4-nitrophenyl)-1,6-dihydropyridine-3-carbonitrile (6o)

It is recrystallized from the class="Chemical">EtOH/class="Chemical">pan class="Chemical">dioxane mixture (1:2) as reddish orange crystals; yield: 1.15 g (83%), mp 298–299 °C; IR (KBr) ν/cm–1: 3457, 3327, 3218, 3137 (2NH2), 2214 (CN), 1659 (CO); 1H NMR (600 MHz, DMSO-d6): δ 2.28 (s, 3H), 6.78 (s, 1H), 7.32 (s, 2H), 7.40 (d, J = 8.4 Hz, 2H), 7.95 (d, J = 8.4 Hz, 2H), 8.08 (d, J = 8.4 Hz, 2H), 8.40 (d, J = 8.4 Hz, 2H), 8.74 (s, 2H); 13C{1H} NMR (150 MHz, DMSO-d6): δ 15, 83.0, 96.3, 110.7, 115.0, 119.5, 123.9, 126.9, 128.4, 130.0, 138.8, 141.9, 147.2, 148.4, 151.0, 153.8, 157.2, 162.4; MS (EI): m/z (%) 462 (M+ + 1, 8.01), 461 (M+, 23.85), 446 (M+ – 15, 100). HRMS (EI): m/z calcd for C22H16ClN7O3 (M+) 461.0998; found, 461.0997.

(Z)-1,2-Diamino-6-[1-(4-chlorophenyl)-3-methyl-5-oxo-1H-pyrazol-4(5H)-ylidene]-4-phenyl-1,6-dihydropyridine-3-carbonitrile (6p)

It is recrystallized from the class="Chemical">EtOH/class="Chemical">pan class="Chemical">dioxane mixture (1:1) as bright orange crystals; yield: 1.0 g (81%), mp above 300 °C; IR (KBr) ν/cm–1: 3410, 3349, 3290, 3154 (2NH2), 2208 (CN), 1656 (CO); 1H NMR (600 MHz, DMSO-d6): δ 2.28 (s, 3H), 6.72 (s, 1H), 7.31 (s, 2H), 7.41 (d, J = 9.0 Hz, 2H), 7.58–7.59 (m, 3H), 7.68–7.69 (m, 2H), 8.10 (d, J = 9.0 Hz, 2H), 8.61 (s, 2H); 13C{1H} NMR (150 MHz, DMSO-d6): δ 15.6, 83.2, 95.9, 110.6, 115.3, 119.5, 126.8, 128.3, 128.4, 128.9, 130.5, 135.6, 138.9, 147.2, 153.3, 153.6, 157.3, 162.4; MS (EI): m/z (%) 417 (M+ + 1, 4.75), 416 (M+, 14.28), 401 (M+ – 15, 100). HRMS (EI): m/z calcd for C22H17ClN6O (M+) 416.1147; found, 416.1148.

(Z)-1,2-Diamino-4-(4-chlorophenyl)-6-(5-oxo-1,3-diphenyl-1H-pyrazol-4(5H)-ylidene)-1,6-dihydropyridine-3-carbonitrile (6q)

It is recrystallized from the class="Chemical">EtOH/class="Chemical">pan class="Chemical">dioxane mixture (1:2) as red crystals; yield: 1.05 g (75%), mp 294–295 °C; IR (KBr) ν/cm–1: 3415, 3313, 3275, 3112 (2NH2), 2212 (CN), 1637 (CO); 1H NMR (600 MHz, DMSO-d6): δ 5.93 (s, 1H), 7.14 (t, J = 7.2 Hz, 1H), 7.21 (d, J = 8.4 Hz, 2H), 7.39–7.44 (m, 5H), 7.49–7.50 (m, 4H), 7.59 (d, J = 7.2 Hz, 2H), 8.10 (d, J = 8.4 Hz, 2H), 8.71 (s, 2H); 13C{1H} NMR (150 MHz, DMSO-d6): δ 83.0, 94.2, 112.6, 115.1, 118.7, 123.7, 128.2, 128.4, 128.5, 128.8, 129.5, 133.9, 134.2, 135.3, 139.9, 149.7, 150.7, 154.2, 157.2, 162.5; MS (EI): m/z (%) 480 (M+ + 2, 35.29), 479 (M+ + 1, 31.25), 478 (M+, 100). HRMS (EI): m/z calcd for C27H19ClN6O (M+) 478.1303; found, 478.1303.

(Z)-1,2-Diamino-4-(4-bromophenyl)-6-(5-oxo-1,3-diphenyl-1H-pyrazol-4(5H)-ylidene)-1,6-dihydropyridine-3-carbonitrile (6r)

It is recrystallized from the class="Chemical">EtOH/class="Chemical">pan class="Chemical">dioxane mixture (1:3) as reddish brown crystals; yield: 1.20 g (77%), mp 274–275 °C; IR (KBr) ν/cm–1: 3439, 3325, 3264, 3110 (2NH2), 2213 (CN), 1642 (CO); 1H NMR (600 MHz, DMSO-d6): δ 5.92 (s, 1H), 7.13–7.15 (m, 3H), 7.39–7.45 (m, 5H), 7.49 (s, 2H), 7.58 (d, J = 7.8 Hz, 2H), 7.63 (d, J = 8.4 Hz, 2H), 8.10 (d, J = 7.8 Hz, 2H), 8.71 (s, 2H); 13C{1H} NMR (150 MHz, DMSO-d6): δ 82.9, 94.2, 112.5, 115.1, 118.7, 123.7, 124.0, 128.2, 128.4, 128.5, 129.7, 131.7, 133.9, 134.6, 139.9, 149.8, 150.7, 154.2, 157.2, 162.5; MS (EI): m/z (%) 524 (M+ + 2, 53.68), 523 (M+ + 1, 19.25), 522 (M+, 51.17), 509 (100). HRMS (EI): m/z calcd for C27H19BrN6O (M+) 522.0798; found, 522.0797.

(Z)-1,2-Diamino-4-(4-fluorophenyl)-6-(5-oxo-1,3-diphenyl-1H-pyrazol-4(5H)-ylidene)-1,6-dihydropyridine-3-carbonitrile (6s)

It is recrystallized from the class="Chemical">EtOH/class="Chemical">pan class="Chemical">dioxane mixture (1:1) as orange crystals; yield: 1.00 g (73%), mp 288–289 °C; IR (KBr) ν/cm–1: 3407, 3343, 3278, 3119 (2NH2), 2212 (CN), 1636 (CO); 1H NMR (600 MHz, DMSO-d6): δ 5.93 (s, 1H), 7.14 (t, J = 7.2 Hz, 1H), 7.23–7.28 (m, 4H), 7.39–7.46 (m, 5H), 7.49 (s, 2H), 7.59 (d, J = 7.2 Hz, 2H), 8.10 (d, J = 7.8 Hz, 2H), 8.68 (s, 2H); 13C{1H} NMR (150 MHz, DMSO-d6): δ 83.2, 94.2, 112.7, 115.3, (115.87, 116.01) (d, 2JCF = 21.0 Hz), 118.8, 123.8, 128.3, 128.5, 128.6, (130.19, 130.25) (d, 3JCF = 9.0 Hz), 131.9, 134.0, 140.0, 149.8, 151.0, 154.2, 157.3 162.6, (162.36, 164.01) (d, 1JCF = 247.5 Hz); MS (EI): m/z (%) 463 (M+ + 1, 22.08), 462 (M+, 76.02), 447 (M+ – 15, 100). HRMS (EI): m/z calcd for C27H19FN6O (M+) 462.1599; found, 462.1598.