Efficient and "Green" Synthetic Route to Imidazo[1,2-a]pyridine by Cu(II)-Ascorbate-Catalyzed A3-Coupling in Aqueous Micellar Media.

An efficient and environmentally sustainable method for the synthesis of imidazo[1,2-a]pyridine derivatives by domino A3-coupling reaction catalyzed by Cu(II)-ascorbate was developed in aqueous micellar media in the presence of sodium dodecyl sulfate (SDS). The catalyst, a dynamic combination of Cu(II)/Cu(I), was generated in situ in the reaction mixture by mixing CuSO4 with sodium ascorbate and aided a facile 5-exo-dig cycloisomerization of alkynes with the condensation products of 2-aminopyridines and aldehydes to afford a variety of imidazo[1,2-a]pyridines in good overall yields. A simple experimental setup, water as the "green" medium, and inexpensive catalyst and auxiliary are some of the merits of this protocol.

Introduction

Imidazopyridine, a nitrogen-fused bicyclic system containing an imidazole moiety fused with pyridine is a common structural scaffold in many biologically active compounds and natural products.[1] Prominent among them are imidazo[1,2-a]pyridines which are of great pharmaceutical interest as they show a broad range of pharmacological activities.[2] They have also shown their potential to act as β-amyloid formation inhibitors,[3a] GABA and benzodiazepine receptor agonists,[3b] cardiotonic agents,[3c] and so on.[3] Many commercially available drugs, such as zolpidem (for insomnia), alpidem (anxiolytic agents), zolimidine (for peptic ulcer) contain imidazo[1,2-a]pyridine moiety (Figure ).[4] In addition, molecular architectures that incorporate the imidazo[1,2-a]pyridine moiety in the framework have demonstrated potential applicability in optoelectronics, dyes, and sensing materials.[5]

Figure 1

Structure of biologically active imidazo[1,2-a]pyridines.

Owing to their vast applications, tremendous research interest has been expressed to develop clean and efficient synthetic methodologies for imidazo[1,2-a]pyridines.[4] Classical synthetic routes to imidazo[1,2-a]pyridines include condensation followed by heterocyclization of 2-aminopyridines with α-haloketones[6] or α,β-unsaturated carbonyl compounds.[7] Apart from this, several other interesting approaches, such as multicomponent reactions, tandem sequences, and transition-metal-catalyzed C–H functionalizations have been developed for this heterocycle, mostly in conventional reaction media.[4,8] Among vast literature, our interest was focused on A3-coupling reactions to afford this heterocycle via 5-exo-dig cyclization.[4,9] After the elegant work of Gevorgyan and Chernyak,[9a] various other catalytic methods have been developed in conventional media which include CuSO4–TsOH in refluxing toluene,[9b] Cu(I)–NaHSO4–SiO2 in toluene,[9c] InBr3 in refluxing toluene,[9d] iron oxide nanoparticles in refluxing toluene,[9e] and so on.[4,9f−9i] However, these methods have one or more shortcomings such as requirement of dry conditions, use of hazardous organic solvents, Brønsted acids, high temperature, and so forth.

With the realization of the concept of “green chemistry”[10] and with its emerging demands in the present day in order to protect our environment, significant research efforts have been focused on the replacement of hazardous organic solvents and reagents with nontoxic chemicals and environmentally benign solvents for any chemical transformation. In particular, the solvent is a crucial factor in any chemical transformation which accounts for the generation of up to 85% of the waste.[11] The most promising alternative is to replace organic solvents by water. In many cases, the immiscibility of the organic components in aqueous media is addressed by the use of surfactants which form micelles or other assemblies, and bring the substrates in the “nanoconfined” hydrophobic cores and thereby, facilitate organic transformations.[12] Over decades, “micellar catalysis” has emerged as a sustainable alternative to various conventional reactions.[13]

Although few green protocols are available for the synthesis of imidazo[1,2-a]pyridines on heterogeneous supports, they involve the synthesis of complex Cu catalysts, making them more expensive methods.[14] However, several commercially available copper salts are very cheap and water soluble, rendering easy recovery of products. Another interesting method reported by Siddiqui et al.,[15] the only metal-free A3-coupling of this kind, involves mild oxidant I2 to act as a catalyst to afford imidazo[1,2-a]pyridines at a surprisingly low temperature. However, to our dismay, we failed to obtain any desired product following their methodology for several attempts on different substrates, even under refluxing conditions. The reactions partly proceed up to the formation of condensation products only, presumably because of limited contact of the catalyst, iodine with water-insoluble reaction intermediates. Based on the above facts, we envisaged that the development of a mild and green protocol for imidazo[1,2-a]pyridines by domino A3-coupling involving inexpensive catalysts will be a worthy pursuit. As part of our continued efforts in the development of environmentally sustainable methods in “micellar media”,[16] we report herein, CuSO4–ascorbate catalyzed synthesis of imidazo[1,2-a]pyridines in water in the presence of sodium dodecyl sulfate (SDS) as the surfactant (Scheme ). CuSO4–ascorbate was envisaged as the catalyst based on the fact that a combination of Cu(II)/Cu(I) works better than a single Cu(I) catalyst.[9f,9h]

Scheme 1

General Scheme for the Synthesis of Imidazo[1,2-a]pyridines in Aqueous Micellar Media

Results and Discussion

At the outset, efforts were put together in optimizing the reaction condition. 2-aminopyridine (1a), benzaldehyde (2a), and phenylacetylene (3a) were selected as the substrates for model reactions during initial investigations of the A3-coupling reaction. The investigation was begun with examining the formation of emulsion droplets of different surfactants containing aqueous solutions of reaction mixtures after 5 min of stirring at room temperature under an optical microscope (Figure a). Dynamic light scattering (DLS) experiments of typical reaction mixtures revealed that the size of emulsion droplets is in the nanometer range with the presence of smaller (20–40 nm) and larger droplets (100–800 nm) with an average diameter of 461 nm (Figure b).

Figure 2

(a) A typical optical micrograph of nanoreactors formed in an aqueous solution of SDS, 2-aminopyridine, benzaldehyde, and phenyl acetylene. (b) DLS data of SDS showing micellar aggregates; the average size is 461 nm.

Next, a thorough screening of various surfactants, catalysts, and reaction temperature was done to arrive at the optimum condition of the A3-coupling reaction. Four different classes of surfactants, viz. SDS (anionic), cetyl trimethylammonium bromide (CTAB, cationic), Triton X-100 and Tween 20 (neutral), and p-dodecylbenzenesulfonic acid (DBSA, Brønsted acid) were selected, and model reactions were conducted in the presence of 10 mol % of different surfactants and CuSO4–ascorbate as the catalyst, first at room temperature and then under mild heating (upto 50 °C). To our delight, the anionic surfactant, SDS could efficiently provide a micellar media to allow the reaction to proceed forward and afford the desired product (4a) in excellent yields at 50 °C after 6 h (Table , entry 3). It was observed that imine formation takes place within 30 min and the reaction proceeds further to form the A3-coupled product (4a). In a separate reaction, under similar conditions, the condensation product of 2-aminopyridine (1a) and benzaldehyde (2a) was isolated and confirmed by 1H NMR. Although the yield is less, the neutral surfactants were also found effective for the coupling reaction (Table , entry 5 and 6). As expected, the reaction was very sluggish in the absence of surfactants even at 80 °C after 24 h, yielding only 14% of 4a (Table , entry 1). This implies that the micellar “nanoreactors”[12] are necessary to bring together water-insoluble components in their hydrophobic core and facilitate the reaction to proceed forward. The reaction in the presence of SDS at a higher temperature did not afford better yield of 4a (Table , entry 4). The same reaction in the presence of CTAB did not proceed well (Table , entry 7).

Table 1

Optimization of Domino A3-Coupling Reaction in Aqueous Micellar Mediaa

entry	surfactant (mol %)	Cu-catalyst (mol %)	reducing agent (mol %)	temp (°C)	time (h)	yield % of 4b
1		CuSO4·5H2O (10)	NaOAs (20)	80	24	14c,d
2	SDS (10)	CuSO4·5H2O (10)	NaOAs (20)	rt	24	21c,d
3	SDS (10)	CuSO4·5H2O (10)	NaOAs (20)	50	6	88
4	SDS (10)	CuSO4·5H2O (10)	NaOAs (20)	80	5	84
5	Triton X-100 (10)	CuSO4·5H2O (10)	NaOAs (20)	50	24	48e
6	Tween 20 (10)	CuSO4·5H2O (10)	NaOAs (20)	50	24	32e
7	CTAB (10)	CuSO4·5H2O (10)	NaOAs (20)	50	6	trace
8	DBSA (10)	CuSO4·5H2O (10)	NaOAs (20)	50	6	12
9	SDS (5)	CuSO4·5H2O (5)	NaOAs (10)	50	6	51
10	SDS (20)	CuSO4·5H2O (10)	NaOAs (20)	50	6	87
11	SDS (10)	CuI (10)		50	24	66
12	SDS (10)	CuBr (10)		50	24	55
13	SDS (10)	CuCl (10)		50	24	71
14	SDS (10)	CuSO4·5H2O (10)		80	24	tracec
15	SDS (10)	CuSO4·5H2O (5)	NaOAs (10)	80	24	68e
16	SDS (10)	CuSO4·5H2O (10)	NaOAs (40)	50	6	80
17	SDS (10)	CuSO4·5H2O (10)	d-Glucose (20)	80	12	72
18	SDS (10)	CuSO4·5H2O (10)	sodium-citrate (20)	80	24	22c

1 mmol 1a, 1 mmol 2a, and 1.2 mmol 3a were taken in 2 mL of water and the reaction was carried out; NaOAs = sodium ascorbate.

Isolated yields.

Major product was imine.

Upto 40% of the starting material was recovered after aforementioned time.

Some imine was left in the reaction mixture as per TLC.

Presumably, electrostatic repulsion of positively charged CTAB with copper ions prevents the catalyst to penetrate into the “nanoreactor”. Similarly, DBSA was not found to be a suitable choice as it may protonate 2-aminopyridine (2a) and inhibit further progress of the reaction (Table , entry 8). Next, focus was paid in identifying the most suitable copper catalyst for the said reaction. Initially, various Cu(I) salts were used for the reaction and up to 71% of the yield of 4a was observed but the rate of the reaction significantly slowed down (Table , entries 11–13). However, only the Cu(II) salt failed to produce measurable amount of the desired product; the reaction did not proceed after imine formation (Table , entry 14). Other than sodium ascorbate, d-glucose and sodium citrate were used as reducing agents. Although d-glucose could afford 4a in 72% yield (but only after 12 h) (Table , entry 17), sodium citrate was found to be not suitable for the same as the major product was imine even after 24 h (Table , entry 18). By varying the mol % of sodium ascorbate (NaOAs), it was found that the use of 20 mol % NaOAs is ideal for A3-coupling of this kind (Table , entries 3,15,16). Therefore, for further investigations, a combination of 10 mol % SDS, 10 mol % CuSO4·5H2O, and 20 mol % of NaOAs was considered as the optimum catalyst concentration, and the reaction temperature was set at 50 °C.

Under the optimized condition, the method was validated with various 2-aminopyridines (1) and aromatic aldehydes (2) in the presence of phenylacetylene (3a) to afford a large variety of imidazo[1,2-a]pyridines (4) in good to excellent yields (Table ). All the imidazo[1,2-a]pyridine derivatives were thoroughly characterized by 1H NMR, 13C NMR, and HRMS analysis. The 1H and 13C NMR spectra were in good agreement with the reported values of the known compounds. The appearance of a characteristic benzylic (−CH2−) singlet peak within a range δ 4.20–4.66 ppm confirmed the formation of imidazo[1,2-a]pyridine derivatives. The same characteristic peak appeared at around δ 30 ppm in 13C NMR of all compounds. In general, the electron-donating (Table , 4q–z) or mild electron-withdrawing substituent (Table , 4aa–ah) on the 2-aminopyridines does not have any significant effect on the reaction rate or yield of the products. It was observed that the reaction takes relatively longer time to complete when strong electron-withdrawing groups are present in the aromatic ring of the aldehyde (Table , 4f–k, 4s, 4x–z, 4af–ah) as compared to those having electron-donating groups (Table , 4b–e, 4ac,ad). It is also noteworthy to mention that relatively unstable heteromatic aldehydes such as furfural and thiophene-2-carboxyaldehye participated in the reaction with equal efficiency to afford corresponding imidazo[1,2-a]pyridine derivatives in good yields (Table , 4o,p). However, reactions involving N-heteroaromatic aldehydes, such as indole-2-carboxyaldehyde and pyrrole-2-carboxyaldehyde, were not fair as they generate a nonisolable complex mixture of products presumably because of the interference of competing amine residue in the heteroaromatic ring. The same methodology was extended to representative aliphatic aldehydes, and, in general, good yields were obtained for the desired product (Table , 4ai–am).

Table 2

Synthesis of Imidazo[1,2-a]pyridine Derivatives (4)a

All yields refer to an isolated product.

Based on the above results, a plausible mechanism has been proposed for this domino A3-coupling reaction (Scheme ). The reaction is initiated by the formation of the condensation products of 2-aminopyridines (1) and aromatic aldehydes (2) inside the hydrophobic core of the micelle. This “dehydration” step is facilitated by the micelle as the product water molecule is immediately ejected out of the hydrophobic core, shifting the equilibrium toward the forward direction. On the other hand, the catalyst, which is a dynamic combination of Cu(II)/Cu(I), is generated in situ in the reaction mixture by mixing CuSO4 with sodium ascorbate and reacts with alkyne to produce copper acetylide. This species undergoes a facile 5-exo-dig cycloisomerization with the intermediate condensation products of 2-aminopyridines and aromatic aldehydes to afford a large variety of imidazo[1,2-a]pyridines via a 1,3-hydride shift.

Scheme 2

Plausible Mechanistic Pathway

Inspired by the recent reports of Gevorgyan and Chernyak,[9a,9h] our methodology was successfully extended to synthesize a small library of 2-(aryl-imidazo[1,2-a]pyridin-3-yl)acetates (5a–k) by the reactions of 2-aminopyridines (1) and aromatic aldehydes (2) with ethyl propiolates (3b) (Table ). The desired product (5) was obtained in moderate to good yields after 8–14 h of stirring at 50 °C. It was found that substituents in the aromatic ring of the aldehydes hardly have any effect in terms of rate of reaction or yield of the product (Table , 5b–f). A similar trend was observed in variation of substituents in the 2-aminopyridine residue (Table , 5g–k). However, the yield of product 5 is, in general, less than imidazo[1,2-a]pyridines derived from phenylacetylene (4).

Table 3

Synthesis of 2-(Aryl-imidazo[1,2-a]pyridin-3-yl)acetates Using Ethyl Propiolate (5)a

All yields refer to an isolated product.

Next, we paid attention on utilizing the reaction media for subsequent reactions from the perspective of atom economy in a chemical process. As the surfactants are highly soluble in water and the products can be simply extracted by organic solvents, a study was conducted to reuse the reaction media for the next cycles using our model substrates (see the Supporting Information, Table S1). It was observed that the reaction media can be reused up to the third cycle without addition of surfactants with no change in yields and minor difference in reaction time. However, concentration of the active catalyst diminishes significantly after each cycle as 10 mol % catalyst loading was mandatory to achieve similar yield as the first cycle (Supporting Information, Table S1, entry 4). It was observed that some brown-black particles precipitated out from the aqueous reaction media after extraction of the crude product with organic solvent, which was isolated and characterized as Cu(0) nanoparticles by X-ray diffraction-analysis (Supporting Information, Figure S1). Atomic absorption spectroscopy (AAS) studies also revealed reduced copper level in the aqueous reaction media after the work-up, indicating the requirement of a fresh batch of CuSO4–NaOAs to achieve similar efficiency of the catalytic process (Supporting Information, Table S2). The present method was compared with available domino A3-coupling methods for the synthesis of 2,3-disubstituted imidazo[1,2-a]pyridines in conventional media[9] and “green” media,[14] and their E-factors were calculated based on a common reaction (Supporting Information, Table S3). As expected, the present method was found to have lower a E-factor than all conventional methods and several “green” methods. It is noteworthy to mention that the present method uses mild heating (50 °C) to achieve the final product in good yields, whereas other available methods generally use refluxing conditions.[9] A scale-up reaction was also conducted in gram scale using 2-aminopyridine (1a, 20 mmol), benzaldehyde (2a, 20 mmol), and phenylacetylene (3a, 24 mmol), and it was observed that the yield and reaction time remain similar (yield 87%; time 6 h), indicating that these reactions can be conducted on large scales.

Conclusions

In conclusion, we have demonstrated a highly efficient and versatile method for the synthesis of imidazo[1,2-a]pyridine derivatives by Cu(II)–ascorbate-catalyzed domino A3-coupling reaction in aqueous micellar media. Presumably, a dynamic combination of Cu(II)/Cu(I), generated in situ by the reaction of CuSO4 with sodium ascorbate, catalyzes a facile 5-exo-dig cycloisomerization of alkynes with the condensation products of 2-aminopyridines and aromatic aldehydes. The methodology works well with aliphatic, aromatic, and heteroaromatic aldehydes. The method can tolerate both electron-withdrawing and electron-donating substituents on 2-aminopyridine and benzaldehyde derivatives to afford the desired products in good overall yields. As the products can be simply extracted in an organic layer, the aqueous part containing the surfactant can be reused for further reactions with the addition of a fresh batch of CuSO4–NaOAs. A scale-up reaction demonstrates that the methodology can be applied in gram-scale without any significant difference in yield and reaction time. The current methodology is superior to existing methods because of the simple experimental setup, use of water as “green” media, mild condition, inexpensive catalyst, and high yields.

Experimental Section

General Information

All reagents were purchased from commercial sources and were used without further purification. All solvents were obtained from local suppliers and were of research grade. The reactions were monitored by thin layer chromatography (TLC) carried out on 0.25 mm silica gel aluminum plates (60F-254) using UV light (254 or 365 nm) for visualization. Column chromatography was performed using 60–120 mesh silica gel. 1H NMR and 13C NMR spectra were recorded on Bruker AVANCE (400 MHz) with tetramethylsilane as the internal standard. Chemical shifts are reported in parts per million (δ) units. Standard abbreviations are used for representing multiplicity of NMR peaks. HRMS spectra were recorded on Q-TOF LC–MS (6545 Q-TOF LC–MS, Agilent) using ESI as the ion source. IR spectra were recorded in KBr pellets with IR Affinity 1, Shimadzu. Particulate Systems NanoPlus zeta/nanoparticle analyzer was used for the DLS study. Olympus IX51 optical microscope was used for capturing microscopic images. AAS studies were performed on AA-7000 atomic absorption spectrophotometer (Shimadzu, Japan).

General Procedure for the Synthesis of Imidazo[1,2-a]pyridines

In a 10 mL round bottom flask, SDS (10 mol %) was added in 2 mL water and the solution was vigorously stirred for 5 min. Then, 2-aminopyridine derivative (1, 1 mmol), aldehyde (2, 1 mmol), CuSO4·5H2O (10 mol %), and sodium ascorbate (20 mol %) were added to the reaction mixture, followed by the addition of the alkyne derivative (1.2 mmol). The reaction mixture was then stirred at 50 °C for 6–16 h, and progress of the reaction was monitored by TLC after each hour. The crude products were extracted from the aqueous phase by ethyl acetate (2 × 10 mL), washed with brine, dried over anhydrous sodium sulphate, and concentrated in vacuum to afford the crude imidazo[1,2-a]pyridine derivative. The crude product was purified by column chromatography (silica gel, 60–120 mesh) using ethyl acetate–petroleum ether as the eluent.

Spectral Data of New Entries

3-Benzyl-2-(4-isopropylphenyl)H-imidazo[1,2-a]pyridine (4d)

Light grey solid; mp 100–102 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) 1.27 (d, J = 6.8 Hz, 6H), 2.94 (sep, J = 6.8 Hz, 1H), 4.49 (s, 2H), 6.68 (dt, J1 = 0.8 Hz, J2 = 6.8 Hz, 1H), 7.13–7.18 (m, 3H), 7.24–7.26 (m, 1H), 7.28–7.32 (m, 4H), 7.67 (d, J = 7.2 Hz, 1H), and 7.71–7.73 (m, 3H); 13C NMR (100 MHz, CDCl3): δ (ppm) 24.0, 29.9, 33.9, 112.2, 117.4, 117.5, 123.4, 124.2, 126.8, 126.9, 127.7, 128.2, 129.0, 136.9, 144.2, 144.8, and 148.5; IR (KBr) ν̃: 3080, 3032, 2954, 2866, 1629, 1500, 1451, 1357, 1259, 850, and 722 cm–1; HRMS (ESI): calcd for C23H22N2 [M + H]+, 327.1856; found, 327.1855.

3-Benzyl-2-(2,5-dimethoxyphenyl)H-imidazo[1,2-a]pyridine (4e)

Light yellow solid; mp 102–104 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) 3.57 (s, 3H), 3.78 (s, 3H), 4.29 (s, 2H), 6.66 (dt, J1 = 1.2 Hz, J2 = 6.4 Hz, 1H), 6.87–6.92 (m, 2H), 7.10–7.16 (m, 3H), 7.18–7.21 (m, 2H), 7.23–7.27 (m, 2H), and 7.66 (dt, J1 = 1.2 Hz, J2 = 6.8 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ (ppm) 30.3, 55.8, 55.9, 111.9, 112.2, 115.1, 117.0, 117.6, 119.8, 123.5, 123.6, 124.4, 126.5, 128.0, 128.7, 137.3, 141.3, 144.8, 151.2, and 153.6; IR (KBr) ν̃: 3058, 3020, 2940, 2836, 1583, 1505, 1356, 1275, 1212, 812, and 742 cm–1; HRMS (ESI): calcd for C22H20N2O2 [M + H]+, 345.1598; found, 345.1602.

3-Benzyl-2-((Z)-1-phenylprop-1-en-2-yl)H-imidazo[1,2-a]pyridine (4n)

Off white solid; mp 68–72 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) 2.47 (s, 3H), 4.49 (s, 2H), 6.68 (dt, J1 = 0.8 Hz, J2 = 6.8 Hz, 1H), 6.88 (d, J = 1.2 Hz, 1H), 7.10 (d, J = 7.2 Hz, 2H), 7.15 (ddd, J1 = 1.2 Hz, J2 = 7.2 Hz, J3 = 8.4 Hz, 1H), 7.22–7.25 (m, 2H), 7.27–7.30 (m, 2H), 7.34 (d, J = 1.2 Hz, 2H), 7.35 (s, 2H), and 7.66 (dd, J1 = 8.8 Hz, J2 = 13.6 Hz, 2H) for major isomer; 13C NMR (100 MHz, CDCl3): δ (ppm) 18.1, 30.1, 112.1, 117.4, 117.6, 123.4, 124.1, 126.6, 126.8, 127.7, 127.9, 128.2, 128.6, 129.0, 129.2, 130.0, 131.7, 137.0, 137.8, 144.3, and 147.4 for major isomer; IR (KBr) ν̃: 3061, 3024, 2917, 2852, 1599, 1492, 1357, 1257, and 729 cm–1; HRMS (ESI): calcd for C23H20N2 [M + H]+, 325.1699; found, 325.1700.

3-Benzyl-5-methyl-2-phenylH-imidazo[1,2-a]pyridine (4q)

Grey solid; mp 133–135 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) 2.58 (s, 3H), 4.66 (s, 2H), 6.41 (d, J = 6.8 Hz, 1H), 7.02–7.07 (m, 3H), 7.24 (t, J = 7.2 Hz, 1H), 7.29–7.34 (m, 3H), 7.35–7.39 (m, 2H), 7.58 (d, J = 9.2 Hz, 1H), and 7.65 (td, J1 = 1.2 Hz, J2 = 6.0 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ (ppm) 20.1, 31.7, 113.7, 115.9, 118.9, 126.5, 127.6, 128.5, 128.7, 129.1, 134.7, 136.3, 141.1, 145.8, and 146.9; IR (KBr) ν̃: 3060, 3023, 2915, 2850, 1602, 1512, 1386, 1238, 1141, and 772 cm–1; HRMS (ESI): calcd for C21H18N2 [M + H]+, 299.1548; found, 299.1541.

3-Benzyl-5-methyl-2-p-tolylH-imidazo[1,2-a]pyridine (4r)

Light yellow solid; mp 118–120 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) 2.35 (s, 3H), 2.59 (s, 3H), 4.65 (s, 2H), 6.40 (d, J = 6.8 Hz, 1H), 7.02–7.06 (m, 3H), 7.18 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 7.6 Hz, 1H), 7.31 (t, J = 7.2 Hz, 2H), and 7.55 (t, J = 8.0 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ (ppm) 20.1, 21.2, 31.8, 113.5, 115.8, 118.6, 124.4, 126.4, 127.6, 128.5, 129.0, 129.2, 131.8, 136.2, 137.4, 141.1, 145.9, and 146.8; IR (KBr) ν̃: 3026, 2919, 2852, 1603, 1512, 1449, 1327, 1264, 827, and 728 cm–1; HRMS (ESI): calcd for C22H20N2 [M + H]+, 313.1705; found, 313.1697.

3-Benzyl-2-(4-fluorophenyl)-5-methylH-imidazo[1,2-a]pyridine (4s)

Off-yellow solid; mp 145–147 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) 2.59 (s, 3H), 4.63 (s, 2H), 6.42 (d, J = 6.8 Hz, 1H), 7.02–7.08 (m, 5H), 7.22–7.26 (m, 1H), 7.32 (t, J = 7.2 Hz, 2H), 7.54 (d, J = 9.2 Hz, 1H), and 7.60 (dt, J1 = 2.0 Hz, J2 = 5.6 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ (ppm) 20.1, 31.7, 113.7, 115.4, (d, J = 21.3 Hz), 115.9, 118.7, 124.7, 126.6, 127.5, 129.1, 130.3 (d, J = 8.1 Hz), 130.9 (d, J = 3.2 Hz), 136.2, 140.9, 145.0, 146.8, and 162.5 (d, J = 245.3 Hz); IR (KBr) ν̃: 3033, 2919, 2851, 1604, 1502, 1392, 1223, 1157, 843, and 733 cm–1; HRMS (ESI): calcd for C21H17FN2 [M + H]+, 317.1449; found, 317.1444.

3-Benzyl-6-methyl-2-p-tolylH-imidazo[1,2-a]pyridine (4u)

Brown solid; mp 194–196 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) 2.23 (s, 3H), 2.37 (s, 3H), 4.45 (s, 2H), 7.02 (dd, J1 = 1.2 Hz, J2 = 9.0 Hz, 1H), 7.14 (d, J = 7.2 Hz, 2H), 7.22 (d, J = 7.6 Hz, 2H), 7.24–7.27 (m, 1H), 7.29–7.33 (m, 2H), 7.47 (s, 1H), 7.58 (d, J = 9.2 Hz, 1H), and 7.66 (d, J = 8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ (ppm) 18.4, 21.3, 29.7, 116.8, 117.1, 120.9, 121.7, 126.8, 127.2, 127.7, 127.9, 129.0, 129.3, 131.8, 137.1, 137.3, 143.9, and 144.0; IR (KBr) ν̃: 3027, 2921, 2853, 1603, 1493, 1388, 1262, 1185, 798, and 730 cm–1; HRMS (ESI): calcd for C22H20N2 [M + H]+, 313.1699; found, 313.1694.

3-Benzyl-2-(4-isopropylphenyl)-6-methylH-imidazo[1,2-a]pyridine (4v)

Light yellow solid; mp 129–132 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) 1.27 (d, J = 6.8 Hz, 6H), 2.23 (s, 3H), 2.93 (sep, J = 6.8 Hz, 1H), 4.46 (s, 2H), 7.02 (dd, J1 = 1.6 Hz, J2 = 8.0 Hz, 1H), 7.14 (d, J = 7.6 Hz, 2H), 7.23–7.33 (m, 5H), 7.45 (s, 1H), 7.63 (d, J = 9.2 Hz, 1H), and 7.70 (dt, J1 = 2.0 Hz, J2 = 8.4 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ (ppm) 18.4, 24.0, 29.9, 33.9, 116.8, 117.1, 120.9, 121.8, 126.2, 126.7, 126.8, 127.3, 127.7, 128.0, 129.0, 130.1, 132.0, 137.1, 143.9, and 148.3; IR (KBr) ν̃: 3058, 3023, 2960, 2870, 1602, 1492, 1387, 1274, 800, and 725 cm–1; HRMS (ESI): calcd for C24H24N2 [M + H]+, 341.2012; found, 341.2006.

3-Benzyl-2-(2,5-dimethoxyphenyl)-6-methylH-imidazo[1,2-a]pyridine (4w)

Light yellow solid; mp 120–122 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) 2.21 (s, 3H), 3.54 (s, 3H), 3.77 (s, 3H), 4.26 (s, 2H), 6.85–6.90 (m, 2H), 6.99 (dd, J1 = 1.6 Hz, J2 = 9.2 Hz, 1H), 7.10 (d, J = 7.2 Hz, 2H), 7.17–7.21 (m, 2H), 7.23–7.27 (m, 2H), 7.44 (s, 1H), and 7.57 (d, J = 9.2 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm) 18.4, 30.2, 55.75, 55.83, 112.2, 115.0, 116.9, 119.5, 126.3, 126.7, 128.0, 128.6, 137.5, 141.1, 143.9, 151.3, and 153.6; IR (KBr) ν̃: 3079, 2999, 2943, 2830, 1601, 1501, 1347, 1275, 1217, 1039, and 799 cm–1; HRMS (ESI): calcd for C23H22N2O2 [M + H]+, 359.1754; found, 359.1754.

3-Benzyl-2-(2-chlorophenyl)-6-methylH-imidazo[1,2-a]pyridine (4x)

Light grey solid; mp 130–132 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) 2.22 (s, 3H), 4.25 (s, 2H), 7.02 (dd, J1 = 1.6 Hz, J2 = 9.2 Hz, 1H), 7.06 (d, J = 6.8 Hz, 2H), 7.16–7.26 (m, 3H), 7.29–7.32 (m, 2H), 7.46–7.49 (m, 2H), 7.51–7.54 (m, 1H), and 7.57 (d, J = 9.2 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm) 18.4, 29.9, 117.1, 119.3, 121.3, 121.8, 126.58, 126.63, 127.2, 127.9, 128.7, 129.4, 129.7, 132.6, 133.9, 134.1, 136.8, 142.0, and 143.8; IR (KBr) ν̃: 3062, 3027, 2921, 2851, 1604, 1494, 1386, 1192, 1045, 799, and 703 cm–1; HRMS (ESI): calcd for C21H17ClN2 [M + H]+, 333.1153; found, 333.1147.

3-Benzyl-2-(4-bromophenyl)-6-methylH-imidazo[1,2-a]pyridine (4y)

Light grey solid; mp 158–160 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) 2.23 (s, 3H), 4.42 (s, 2H), 7.04 (dd, J1 = 1.6 Hz, J2 = 9.2 Hz, 1H), 7.12 (d, J = 7.2 Hz, 2H), 7.24–7.33 (m, 3H), 7.48 (s, 1H), 7.51 (td, J1 = 1.6 Hz, J2 = 8.4 Hz, 2H), 7.57 (d, J = 9.2 Hz, 1H), and 7.63 (td, J1 = 1.6 Hz, J2 = 8.4 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ (ppm) 18.4, 29.8, 116.9, 117.6, 120.9, 121.7, 122.1, 127.0, 127.6, 129.1, 129.6, 131.7, 133.7, 136.7, 142.8, and 144.1; IR (KBr) ν̃: 3080, 3025, 2918, 2852, 1693, 1485, 1382, 1260, 1068, and 801 cm–1; HRMS (ESI): calcd for C21H17BrN2 [M + H]+, 377.0648 (for 79Br) and 379.0633 (for 81Br); found, 377.0640 (for 79Br), 379.0621 (for 81Br).

3-Benzyl-6-chloro-2-p-tolylH-imidazo[1,2-a]pyridine (4ab)

Off-white solid; mp 168–172 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) 2.38 (s, 3H), 4.45 (s, 2H), 7.11–7.13 (m, 3H), 7.22–7.28 (m, 3H), 7.30–7.34 (m, 2H), 7.60 (dd, J1 = 0.8 Hz, J2 = 9.2 Hz, 1H), 7.66 (d, J = 8.0 Hz, 2H), and 7.71 (d, J = 1.2 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm) 21.3, 29.9, 117.8, 118.1, 120.3, 121.1, 125.3, 127.1, 127.7, 128.0, 129.2, 129.4, 131.2, 136.3, 137.8, 143.2, and 145.3; IR (KBr) ν̃: 3136, 3023, 2912, 2850, 1601, 1493, 1389, 1260, 1092, 795, and 731 cm–1; HRMS (ESI): calcd for C21H17ClN2 [M + H]+, 333.1153; found, 333.1149.

3-Benzyl-6-chloro-2-(4-isopropylphenyl)H-imidazo[1,2-a]pyridine (4ac)

Off-white solid; mp 152–154 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) 1.27 (d, J = 6.8 Hz, 6H), 2.94 (sep, J = 6.8 Hz, 1H), 4.46 (s, 2H), 7.11–7.14 (m, 3H), 7.25–7.34 (m, 5H), 7.61 (dd, J1 = 0.4 Hz, J2 = 9.6 Hz, 1H), and 7.69–7.72 (m, 3H); 13C NMR (100 MHz, CDCl3): δ (ppm) 23.9, 29.9, 33.9, 117.8, 118.1, 120.3, 121.1, 125.3, 126.8, 127.1, 127.7, 128.1, 129.2, 131.6, 136.3, 143.2, 145.4, and 148.8; IR (KBr) ν̃: 3082, 3027, 2961, 2867, 1523, 1494, 1391, 1251, 1093, 798, and 728 cm–1; HRMS (ESI): calcd for C23H21ClN2 [M + H]+, 361.1466; found, 361.1453.

3-Benzyl-6-chloro-2-(2,5-dimethoxyphenyl)H-imidazo[1,2-a]pyridine (4ad)

Off-white solid; mp 120–124 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) 3.56 (s, 3H), 3.78 (s, 3H), 4.26 (s, 2H), 6.87–6.93 (m, 2H), 7.09 (d, J = 6.8 Hz, 3H), 7.18–7.22 (m, 2H), 7.25–7.28 (m, 2H), 7.61 (d, J = 9.6 Hz, 1H), and 7.69 (s, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm) 30.2, 55.76, 55.84, 112.3, 115.4, 117.0, 117.9, 120.2, 120.6, 121.3, 123.9, 124.9, 126.7, 127.9, 128.8, 136.6, 142.4, 143.2, 151.2, and 153.7; IR (KBr) ν̃: 3082, 3002, 2928, 2833, 1601, 1502, 1408, 1325, 1268, 1032, and 799 cm–1; HRMS (ESI): calcd for C23H19ClN2O2 [M + H]+, 379.1208; found, 379.1204.

3-Benzyl-6-chloro-2-(naphthalen-1-yl)H-imidazo[1,2-a]pyridine (4ae)

Light yellow solid; mp 169–170 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) 4.26 (s, 2H), 7.03 (d, J = 8.4 Hz, 2H), 7.17 (dd, J1 = 2.0 Hz, J2 = 9.6 Hz, 1H), 7.20–7.25 (m, 3H), 7.44–7.51 (m, 3H), 7.56 (dd, J1 = 1.2 Hz, J2 = 6.8 Hz, 1H), 7.66 (dd, J1 = 0.8 Hz, J2 = 9.6 Hz, 1H), 7.79 (dd, J1 = 0.8 Hz, J2 = 2.0 Hz, 1H), 7.90 (d, J = 8.4 Hz, 2H), and 8.10 (dd, J1 = 1.2 Hz, J2 = 8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm) 29.7, 118.1, 120.4, 120.6, 121.5, 125.1, 125.4, 125.9, 126.2, 126.5, 126.9, 127.8, 128.1, 128.9, 129.0, 131.3, 132.5, 133.9, 136.2, 143.2, and 144.9; IR (KBr) ν̃: 3057, 3025, 2921, 1602, 1495, 1324, 1266, 1121, and 778 cm–1; HRMS (ESI): calcd for C24H17ClN2 [M + H]+, 369.1153; found, 369.1148.

3-Benzyl-6-chloro-2-(4-fluorophenyl)H-imidazo[1,2-a]pyridine (4af)

Grey solid; mp 118–122 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) 4.44 (s, 2H), 7.09–7.16 (m, 5H), 7.26–7.35 (m, 3H), 7.61 (d, J = 9.6 Hz, 1H), and 7.70–7.74 (m, 3H); 13C NMR (100 MHz, CDCl3): δ (ppm) 29.8, 115.7 (d, J = 21.4 Hz), 117.9, 118.2, 120.6, 121.2, 125.7, 127.2, 127.6, 129.3, 129.8 (J = 8.1 Hz), 130.2 (d, J = 3.1 Hz), 136.0, 143.2, 144.4, and 162.7 (d, J = 246.1 Hz); IR (KBr) ν̃: 3136, 3031, 2923, 1602, 1494, 1330, 1217, 809, and 723 cm–1; HRMS (ESI): calcd for C20H14ClFN2 [M + H]+, 337.0902; found, 337.0898.

3-Benzyl-2-undecylH-imidazo[1,2-a]pyridine (4ai)

Viscous liquid; 1H NMR (400 MHz, CDCl3): δ (ppm) 0.87 (t, J = 6.8 Hz, 3H), 1.24–1.37 (m, 14H), 1.68 (quin, J = 7.6 Hz, 1H), 1.78 (quin, J = 7.6 Hz, 2H), 2.36 (t, J = 7.6 Hz, 1H), 2.82 (t, J = 7.6 Hz, 2H), 4.26 (s, 2H), 6.66 (t, J = 6.8 Hz, 1H), 7.08–7.14 (m, 3H), 7.20–7.23 (m, 1H), 7.25–7.29 (m, 2H), and 7.62–7.66 (m, 2H); 13C NMR (100 MHz, CDCl3): δ (ppm) 14.1, 22.7, 25.2, 27.5, 29.1, 29.4, 29.5, 29.61, 29.64, 29.7, 30.2, 31.9, 111.8, 116.8, 117.5, 123.1, 123.7, 126.8, 127.8, 128.8, 136.9, 144.3, and 145.1; IR (KBr) ν̃: 3050, 2956, 1591, 1470, 1330, 1250, 965, and 790 cm–1; HRMS (ESI): calculated for C25H34N2 [M + H]+, 363.2795; found, 363.2791.

3-Benzyl-6-methyl-2-undecylH-imidazo[1,2-a]pyridine (4aj)

Viscous liquid; 1H NMR (400 MHz, CDCl3): δ (ppm) 0.90 (t, J = 7.2 Hz, 3H), 1.26–1.39 (m, 14H), 1.66–1.72 (m, 1H), 1.78 (quin, J = 7.6 Hz, 2H), 2.23 (s, 3H), 2.34 (t, J = 8.0 Hz, 1H), 2.80 (t, J = 7.6 Hz, 2H), 4.25 (s, 2H), 7.00 (dd, J1 = 1.6 Hz, J2 = 9.2 Hz, 1H), 7.10 (d, J = 7.2 Hz, 2H), 7.24 (d, J = 7.2 Hz, 1H), 7.28–7.31 (m, 2H), 7.44 (s, 1H), and 7.58 (d, J = 9.2 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm) 14.1, 18.3, 22.7, 25.3, 27.5, 29.0, 29.4, 29.5, 29.6, 29.65, 29.67, 30.1, 31.9, 116.1, 117.2, 120.8, 121.4, 126.7, 126.8, 127.8, 128.8, 131.2, 143.3, and 144.8; IR (KBr) ν̃: 3050, 2956, 2902, 1601, 1472, 1327, 1280, 961, and 796 cm–1; HRMS (ESI): calcd for C26H36N2O2 [M + H]+, 377.2957; found, 377.2962.

3-Benzyl-2-cyclohexyl-6-methylH-imidazo[1,2-a]pyridine (4al)

Viscous liquid; 1H NMR (400 MHz, CDCl3): δ (ppm) 1.33–1.36 (m, 4H), 1.46–1.56 (m, 2H), 1.64–1.80 (m, 4H), 2.19 (s, 3H), 2.76–2.83 (m, 1H), 4.25 (s, 2H), 6.96 (dd, J1 = 1.2 Hz, J2 = 9.2 Hz, 1H), 7.07 (d, J = 7.2 Hz, 2H), 7.20–7.23 (m, 1H), 7.26–7.33 (m, 2H), 7.40 (s, 1H), and 7.63 (d, J = 9.2 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm) 18.3, 25.6, 26.0, 26.9, 28.9, 29.2, 33.1, 36.9, 116.0, 116.2, 119.2, 120.8, 121.6, 126.7, 126.9, 127.8, 128.8, 137.2, 143.3, and 149.0; IR (KBr) ν̃: 3055, 3023, 2928, 1591, 1501, 1350, 1192, 955, and 729 cm–1; HRMS (ESI): calcd for C21H24N2 [M + H]+, 305.2012; found, 305.2006.

3-Benzyl-6-chloro-2-cyclohexylH-imidazo[1,2-a]pyridine (4am)

Viscous liquid; 1H NMR (400 MHz, CDCl3): δ (ppm) 1.20–1.30 (m, 2H), 1.33–1.37 (m, 3H), 1.48–1.55 (m, 1H), 1.64–1.70 (m, 2H), 1.75–1.79 (m, 2H), 2.76–2.83 (m, 1H), 4.26 (s, 2H), 7.05–7.08 (m, 3H), 7.23–7.31 (m, 3H), 7.62 (dd, J1 = 0.8 Hz, J2 = 9.6 Hz, 1H), and 7.64 (d, J = 1.2 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm) 25.9, 26.8, 29.0, 29.1, 33.1, 36.9, 117.2, 117.3, 117.4, 120.1, 120.9, 124.8, 127.6, 127.7, 129.0, 136.4, 142.8, and 150.8; IR (KBr) ν̃: 3070, 3025, 2927, 1601, 1495, 1350, 1250, 1155, and 722 cm–1; HRMS (ESI): calcd for C20H21ClN2 [M + H]+, 325.1466; found, 325.1461.

Ethyl 2-(2-(4-Bromophenyl)H-imidazo[1,2-a]pyridin-3-yl)acetate (5e)

Light yellow solid; mp 83–86 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) 1.28 (t, J = 7.2 Hz, 3H), 4.01 (s, 2H), 4.23 (q, J = 7.2 Hz, 2H), 6.89 (dt, J1 = 1.2 Hz, J2 = 8.0 Hz, 1H), 7.23–7.27 (m, 1H), 7.61 (td, J1 = 2.4 Hz, J2 = 8.4 Hz, 2H), 7.66 (d, J = 9.2 Hz, 1H), 7.74 (td, J1 = 2.4 Hz, J2 = 8.4 Hz, 2H), and 8.14 (d, J = 7.2 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm) 14.2, 30.9, 61.8, 112.6, 113.1, 117.7, 122.2, 123.8, 124.8, 130.1, 131.8, 133.1, 143.5, 145.1, and 169.2; IR (KBr) ν̃: 3108, 3086, 2976, 1721, 1485, 1366, 1254, 1026, 827, and 728 cm–1; HRMS (ESI): calcd for C17H15BrN2O2 [M + H]+, 359.039 (for 79Br) and 361.0375 (for 81Br); found 359.0389 (for 79Br) and 361.0370 (for 81Br).

Ethyl 2-(2-(4-Cyanophenyl)H-imidazo[1,2-a]pyridin-3-yl)acetate (5f)

Light yellow solid; mp 92–94 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) 1.30 (t, J = 7.2 Hz, 3H), 4.04 (s, 2H), 4.25 (q, J = 7.2 Hz, 2H), 6.93 (td, J1 = 1.2 Hz, J2 = 6.8 Hz, 1H), 7.27–7.31 (m, 1H), 7.67 (d, J = 8.8 Hz, 1H), 7.77 (d, J = 8.4 Hz, 2H), 8.00 (d, J = 8.4 Hz, 2H), and 8.18 (d, J = 6.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm) 14.2, 30.9, 62.0, 111.4, 113.0, 114.2, 117.8, 118.9, 123.9, 125.4, 129.0, 132.5, 138.7, 142.5, 145.3, and 168.9; IR (KBr) ν̃: 2981, 2926, 2851, 2226, 1733, 1611, 1479, 1365, 1262, 849, and 733 cm–1; HRMS (ESI): calcd for C18H15N3O2 [M + H]+, 306.1237; found, 306.1238.

Ethyl 2-(2-(4-Bromophenyl)-6-methylH-imidazo[1,2-a]pyridin-3-yl)acetate (5h)

Brown solid; mp 137–139 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) 1.23 (t, J = 7.2 Hz, 3H), 2.36 (s, 3H), 4.00 (s, 2H), 4.22 (q, J = 7.2 Hz, 2H), 7.08 (dd, J1 = 1.6 Hz, J2 = 9.2 Hz, 1H), 7.54 (d, J = 9.2 Hz, 1H), 7.58 (td, J1 = 2.4 Hz, J2 = 8.4 Hz, 2H), 7.71 (td, J1 = 2.4 Hz, J2 = 8.4 Hz, 2H), and 7.89 (s, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm) 14.2, 18.5, 30.9, 61.7, 112.8, 116.9, 121.4, 122.0, 122.3, 128.0, 130.0, 131.7, 133.2, 143.3, 144.2, and 169.3; IR (KBr) ν̃: 3079, 2973, 2927, 1725, 1484, 1399, 1247, 1187, 1027, 828, and 791 cm–1; HRMS (ESI): calcd for C18H17BrN2O2 [M + H]+, 373.0546 (for 79Br) and 375.0531 (for 81Br); found, 373.0542 (for 79Br) and 375.0521 (for 81Br).

Ethyl 2-(6-Chloro-2-(4-cyanophenyl)H-imidazo[1,2-a]pyridin-3-yl)acetate (5k)

Brown solid; mp 134–136 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) 1.24 (t, J = 7.2 Hz, 3H), 3.95 (s, 2H), 4.19 (q, J = 7.2 Hz, 2H), 7.17 (dd, J1 = 2.0 Hz, J2 = 9.6 Hz, 1H), 7.53 (dd, J1 = 0.8 Hz, J2 = 9.6 Hz, 1H), 7.69 (td, J1 = 1.6 Hz, J2 = 8.4 Hz, 2H), 7.90 (td, J1 = 1.6 Hz, J2 = 8.4 Hz, 2H), and 8.16 (dd, J1 = 0.8 Hz, J2 = 1.6 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm) 14.2, 30.8, 62.1, 109.5, 111.6, 114.7, 118.2, 118.8, 121.3, 121.9, 126.8, 128.9, 132.5, 137.5, 138.2, 143.4, 143.6, and 168.9; IR (KBr) ν̃: = 3094, 2981, 2924, 2223, 1719, 1609, 1493, 1380, 1265, 1092, and 796 cm–1; HRMS (ESI): calcd for C18H14ClN3O2 [M + H]+, 340.0847; found, 340.0847.