Visible-Light-Induced Dehydrogenative Imidoylation of Imidazo[1,2- a]pyridines with α-Amino Acid Derivatives and α-Amino Ketones

Article

Visible-Light-Induced Dehydrogenative Imidoylation of

Imidazo[1,2‑a]pyridines with α‑Amino Acid Derivatives and

α ‑Amino Ketones

Zhi-Qiang Zhu,* Dong Guo, Jiu-Jian Ji, Xiao Zhu, Juan Tang,* Zong-Bo Xie, and Zhang-Gao Le*

Cite This: https://dx.doi.org/10.1021/acs.joc.0c01940

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sı Supporting Information

ABSTRACT: A new and eﬃcient visible-light-promoted dehydrogenative cross-coupling reaction of imidazo[1,2-a]pyridines with

α-amino carbonyl compounds toward imidoyl imidazo[1,2-a]pyridines is developed. A diverse range of imidazo[1,2-a]pyridines

undergoes the dehydrogenative imidoylation smoothly with α-amino carbonyl compounds to access the corresponding products in

satisfactory yields. We have also proposed the possible reaction mechanism based on preliminary mechanistic studies. The synthetic

method has the advantages of wide substrate scope, good functional tolerance, and mild reaction conditions, which make this

transformation more practical and sustainable.

INTRODUCTION

compounds with various coupling partners to deliver α-

substituted α-amino carbonyl derivatives in the past

■

As an important “privileged scaﬀold”, an imidazo[1,2-a]-

pyridine core is prevalent in a large number of bioactive

pharmaceuticals and nature products. Among them, C-3

functionalized imidazo[1,2-a]pyridines possess various bio-

10,11

decade.

However, the use of α-amino carbonyl compounds

to produce a new C−C or C−heteroatom bond and a C−N

double bond has been rarely studied. For example, in 2012,

Li’s group reported an oxidative α-arylation of α-amino

carbonyl compounds with indoles to produce 2-(1H-indol-3-

logical and pharmaceutical activities, like antibacterial, anti-

inﬂammatory, anti-viral, and anti-cancer. Several commer-

cially available drugs such as alpidem, zolpidem, necopidem,

and saripidem contain the imidazo[1,2-a]pyridine moiety in

12a

yl)-2-iminocarbonyls using a CuCl/TBHP catalytic system.

In 2013, Yang and co-workers described a selective α-

phosphonation of α-amino ketones with diphenylphosphine

oxide to furnish imidoylphosphonates by copper catalysis with

their core structure. In addition, imidazo[1,2-a]pyridine

derivatives have been found to be useful as charge transporters

in materials science. Owing to their importance and

12b

TBHP as an oxidant. Recently, Huang et al. and Xiang et al.

utilizations, tremendous eﬀorts have been made for direct

C−H functionalization of imidazo[1,2-a]pyridines, and sig-

disclosed copper-catalyzed oxidative cross-coupling reactions

of α-amino carbonyl compounds with amines to obtain 2-

12c12d

niﬁcant progress has been achieved in the past few years.

amino-2-iminocarbonyl compounds.,

Visible-light sensi-

Despite these achievements, selective imidoylation of imidazo-

tization to facilitate various organic transformations has

recently emerged as a reliable and attractive synthetic

technology due to its intrinsic characteristics of sustainability

[1,2-a]pyridines with α-amino carbonyl compounds leading to

imidoyl imidazo[1,2-a]pyridines by using a C−H oxidation

strategy has not been established. Therefore, the development

of new and eﬃcient methods toward the synthesis of

potentially useful organic molecules is still highly desired.

Direct dehydrogenative cross-coupling has been considered

as a promising ideal synthetic tool to construct new chemical

bonds because this type of reaction avoids functional group

interconversion and has the advantages of high atomic and step

and green chemistry. In consideration of the biological

Received: August 10, 2020

economy. Much attention has been paid for direct α-

functionalization of the C−H bond in α-amino carbonyl

XXXX American Chemical Society

J. Org. Chem. XXXX, XXX, XXX−XXX

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Article

Table 1. Optimization of the Reaction Conditions

entry

catalyst

eosin Y

additive

C H O ·H O

solvent

yield (%)

CH CN

trace

eosin Y

CH CN

−

Acr -Mes-ClO

C H O ·H O

CH CN

Ir(ppy)₃

C H O ·H O

CH CN

Ru(bpy) Cl ·6H O

C H O ·H O

CH CN

eosin Y

HCOOH

CH CN

CH COOH

CH CN

PhCOOH

CH CN

C H O

CH CN

C H O ·H O

CH CN

C H O ·H O

DMF

C H O ·H O

EtOH

C H O ·H O

eosin Y

Reaction conditions: 1a (0.15 mmol), 2a (0.18 mmol), catalyst (5 mol %), oxidant (2 equiv), additive (1.5 equiv), solvent (2 mL) at room

temperature under the irradiation of 18 W blue LED light for 18−24 h. Isolated yield based on 1a. No additive. Citric acid (C H O ). Under a

nitrogen atmosphere. Citric acid monohydrate (C H O ·H O, 1 equiv). Without irradiation of visible light. In the absence of a catalyst, 37%

yield of product C was isolated.

importance of imidazo[1,2-a]pyridines and as the continuation

Table 1). Without the irradiation of visible light, no desired

product 3aa was detected (entry 14, Table 1). Screening

revealed that lower yields of 3aa were isolated in the absence of

a photosensitizer or an additive (entries 15 and 16, Table 1).

After exploring diﬀerent parameters, the optimized reaction

should be carried out with eosin Y (10 mol %) and citric acid

monohydrate (1.5 equiv) in EtOH under irradiation of 18 W

blue LED light at room temperature. Under the optimized

conditions, various α-amino carbonyl compounds 1 were

investigated in this reaction with 2-phenylimidazo[1,2-a]-

pyridine 2a (Table 2). Initially, steric and electronic variations

in the benzene rings of N-arylglycine ethyl esters 1a−1f were

tested with 2a, and it was observed that the electron-donating

substituents on the benzene rings of N-arylglycine ethyl esters

of our interest in the dehydrogenative cross-coupling

reaction, we herein present our recent work on a green

and novel visible-light-mediated dehydrogenative imidoylation

of imidazo[1,2-a]pyridines with α-amino acid derivatives and

α-amino ketones for imidoyl imidazo[1,2-a]pyridines.

RESULTS AND DISCUSSION

■

Our initial study began with N-(4-methylphenyl)glycine ethyl

ester 1a and 2-phenylimidazo[1,2-a]pyridine 2a under the

catalysis of 10 mol % eosin Y in MeCN at room temperature

(

entry 1, Table 1). To our delight, the desired product 3aa was

formed, albeit in a yield of 14% under illumination of 18 W

blue LED light. Interestingly, product 3aa was isolated in 69%

yield when citric acid monohydrate (C H O ·H O) was used

a−1d led to better yields than the electron-deﬁcient

substituents on the benzene rings of N-arylglycine ethyl esters

g and 1h. Changing the position of the methyl group on the

as an additive (entry 2, Table 1). The structure of 3aa was

con ﬁ rmed by single-crystal X-ray diﬀraction analysis (CCDC

benzene ring of N-arylglycine ester from the para position 1a

to the meta position 1d resulted in diminished yield. The

synthetically valuable functional groups, Cl and Br, could be

well tolerated under the current conditions. Furthermore, N-

arylglycine esters 1i−1l including a series of alkyl substituents

in the ester moiety, like methyl, isopropyl, tert-butyl, and

benzyl, were also able to deliver the desired products 3ia−3la

in satisfactory yields. Moreover, the current dehydrogenative

coupling reaction was found to be eﬃcient for α-amino

ketones 1m and 1n, albeit providing the desired products 3ma

and 3na with relatively lower yields. Unfortunately, when α-

amino alkyl ketone, 1-(p-tolylamino)propan-2-one, was used

instead of 1a with 2a, no desired product was detected by

GC−MS analysis. To demonstrate the practicability of this

protocol, the reaction of glycine ester 1a (5.3 mmol, 1.02 g)

951464 ). Encouraged by these results, several common

−

sensitizers like Acr -Mes-ClO , Ru(bpy) Cl ·6H O, and

Ir(ppy) were investigated, and inferior yields of product 3aa

were displayed (compare entries 3−5 with entry 2, Table 1).

Replacing citric acid monohydrate with other additives such as

HCOOH, CH COOH, PhCOOH, and C H O resulted in

lower yields of 3aa (compare entries 6−9 with entry 2, Table

). A series of oxidants were also examined, and lower yields of

product 3aa were obtained (see the Supporting Information).

No reaction occurred when the reaction was performed in a

nitrogen atmosphere (entry 10, Table 1). Among the solvents

screened, EtOH was proved to be the best for the yield of

product 3aa (compare entries 2 and 11 with entry 12, Table 1;

also see the Supporting Information). A reduction in the

amount of C H O ·H O led to low yield of 3aa (entry 13,

J. Org. Chem. XXXX, XXX, XXX−XXX

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Article

Table 2. Reaction Scope of α-Amino Carbonyl Compounds 1 ^,

a b

Reaction conditions: 1 (0.15 mmol), 2a (0.18 mmol), eosin Y (5 mol %), C H O ·H O (1.5 equiv), EtOH (2 mL) in air at room temperature

under the irradiation of 18 W blue LED light for 18−24 h. Isolated yield based on 1.

with 2-phenylimidazo[1,2-a]pyridine 2a was carried out in a

gram scale, and the desired product 3aa was isolated in 71%

yield (1.45 g).

To evaluate the scope and limitations of the present

protocol, various imidazoheterocycles 2 were examined with

N-(4-methylphenyl)glycine ethyl ester 1a under the current

conditions. As expected, a wide range of imidazoheterocycles

ring were suitable for this transformation, leading to the

corresponding coupling products 3la−3na in good to excellent

yields. Expectedly, 2-methylimidazo[1,2-a]pyridine 2o reacted

with 1a smoothly, aﬀording the coupling product 3oa in a yield

of 50%. 2-Phenyl imidazothiazole 2p was also compatible

under the current conditions, producing the corresponding

product 3pa in 58% yield.

a−2p could be readily transformed into the desired coupling

To better understand the mechanism of this transformation,

some control experiments were carried out and the results are

listed in Scheme 1. Firstly, when TEMPO (2,2,6,6-

tetramethylpiperidinyloxy, a radical inhibitor) was subjected

to the model reaction, no formation of the desired 3aa was

observed (Scheme 1a). The result suggested that a radical

process was possibly involved in the coupling reaction. Next,

we found that N-(4-methylphenyl)glycine ethyl ester 1a could

be converted into imine intermediate 4a, albeit in 15% yield, as

well as a yield of 12% self-cyclization product 5a and other

byproducts (Scheme 1b). Furthermore, when the reaction of

imine 4a with 2-phenylimidazo[1,2-a]pyridine 2a was

conducted under the standard conditions, product 3aa and C

were obtained in 21% and 62% yields, respectively (Scheme

1c). Low yield or a trace amount of 3aa was formed in the

absence of citric acid monohydrate or eosin Y. Moreover,

intermediate C could be transformed into 3aa in 86% yield

under the standard conditions (Scheme 1d). Decreased yields

of 3aa were obtained without the use of citric acid

products 3aa−3pa with 1a in 40−88% yields (Table 3).

Imidazo[1,2-a]pyridines 2b−2f possessing either an electron-

donating group or electron-withdrawing group on benzene

rings reacted eﬃciently with 1a, giving the corresponding

products 3ba−3fa in good to excellent yields. The results

showed that the reactivity of the electron-rich substituent was

superior to that of the electron-deﬁcient substituent on the

benzene rings of imidazo[1,2-a]pyridines, and some halogen

substituents could be tolerated by the reaction. However, when

imidazo[1,2-a]pyridines 2f−2h were utilized under the

standard conditions, products 3af−3ah were isolated in

relatively low yields, and a complex mixture of unidentiﬁed

compounds was formed. On the other hand, imidazo[1,2-

a]pyridines including electron-rich groups on the pyridine

rings 2i−2k displayed better eﬃciency than electron-deﬁcient

groups on the pyridine rings 2g and 2h. The experimental

results also revealed that imidazo[1,2-a]pyridines 2l−2n

bearing substituents on both the benzene ring and pyridine

J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Article

Table 3. Reaction Scope of Imidazoheterocycles 2 ^,

a b

Reaction conditions: 1a (0.15 mmol), 2 (0.18 mmol), eosin Y (5 mol %), C H O ·H O (1.5 equiv), EtOH (2 mL) in air at room temperature

under the irradiation of 18 W blue LED light for 18−24 h. Isolated yield based on 1a.

monohydrate or eosin Y. The abovementioned results

indicated that both eosin Y and citric acid monohydrate

played an important role in this coupling reaction. In addition,

ﬂuorescence quenching experiments with the eosin Y photo-

redox catalyst as well as cyclic voltammetry (CV) experiments

to study the redox potential of substrates were also performed

formed, albeit in a low yield, by the auto-oxidation-promoted

cross-coupling of 1a with 2a through an acid-catalyzed

process, which is followed by further oxidation to aﬀord

the desired product 3aa.

CONCLUSIONS

■

(

see the Supporting Information ). The experimental results

In conclusion, we have developed a novel and eﬃcient visible-

light-induced dehydrogenative imidoylation of imidazo[1,2-

a]pyridines with α-amino carbonyl compounds for the

synthesis of imidoyl imidazo[1,2-a]pyridines. A series of

imidazo[1,2-a]pyridines undergo the dehydrogenative imidoy-

lation well with α-amino carbonyl compounds, aﬀording the

corresponding imidoyl imidazo[1,2-a]pyridines in satisfactory

yields. The synthetic method has the advantages of broad

substrate scope, good functional tolerance, and mild reaction

conditions, thus making this conversion more sustainable and

practical.

revealed that the reaction might proceed through a reductive

quenching pathway.

On the basis of the control experiments and precedent

6−18

literature,

a plausible reaction pathway for the visible-

light-induced dehydrogenative imidoylation of imidazo[1,2-

a]pyridine is depicted in Scheme 2. Initially, upon irradiation,

eosin Y was excited to produce the excited eosin Y, and a single

electron transfer (SET) from N-arylglycine ethyl ester 1a

−

(

+0.81 V vs SCE) to the excited eosin Y (eosin Y*/eosin Y :

·−

0.83 V vs SCE) gave radical cation A and eosin Y . At the

same time, eosin Y was oxidized by molecular oxygen to

generate the ground-state eosin Y and superoxide radical anion

−

EXPERIMENTAL SECTION

General Information. Unless otherwise indicated, all reagents

■

−

(

O₂). Subsequently, radical cation A was converted into

were purchased from commercial distributors and used without

iminium ion intermediate B by interacting with the superoxide

further puriﬁcation. H NMR and C NMR were recorded at 400 or

−

^r^a^dⁱ^c^a^l^aⁿⁱ^oⁿ⁽^O2 ). Next, intermediate B underwent

electrophilic addition with imidazo[1,2-a]pyridine 2a to

generate C. On the other hand, intermediate C could be

500 MHz and 100 or 125 MHz, respectively, using tetramethylsilane

as an internal reference and CDCl as a solvent (unless otherwise

stated). High-resolution mass spectra (HRMS) were measured on a

J. Org. Chem. XXXX, XXX, XXX−XXX

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Article

Scheme 1. Control Experiments

Scheme 2. Plausible Mechanism

quadrupole time-of-ﬂight (Q-TOF) mass spectrometer instrument

with an electrospray ionization (ESI) source. Cyclic voltammograms

were obtained on a CHI 600E potentiostat. Melting points were

uncorrected. Flash column chromatography was performed over silica

gel 200−300 mesh. α-Amino carbonyl compounds 1 and

imidazoheterocycles 2 were prepared according to the previous

reported protocols.

General Procedure for the Synthesis of 3. To a mixture of α-

amino carbonyl compounds 1 (0.15 mmol) and imidazo[1,2-

a]pyridines 2 (0.18 mmol) in EtOH (2 mL) were added eosin Y

(0.0075 mmol, 5.1 mg) and citric acid monohydrate (0.225 mmol,

47.2 mg). Then, the reaction mixture was stirred at room temperature

under air by the irradiation of a single LED light (Ouying Lighting

Co., Ltd., 18 W/5313 A/455 nm) for the time indicated through the

bottom of the vial at a distance of 15 cm. After the reaction was

ﬁnished, the resulting mixture was concentrated under vacuum and

the residue was subjected to column chromatography (silica gel,

J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Article

petroleum ether/ethyl acetate 4:1 as an eluent) to aﬀord the desired

coupling products 3.

Hz, 1H), 7.81 (d, J = 8.8 Hz, 1H), 7.60−7.58 (m, 2H), 7.53−7.48 (m,

1H), 7.41−7.40 (m, 3H), 7.28 (d, J = 8.4 Hz, 2H), 7.07 (td, J = 6.8,

0.8 Hz, 1H), 6.87 (d, J = 8.8 Hz, 2H), 3.36 (q, J = 7.2 Hz, 2H), 0.78

Ethyl 2-(2-phenylimidazo[1,2-a]pyridin-3-yl)-2-(p-tolylamino)-

acetate (3aa). Yield 78% (44.8 mg); light yellow solid; mp:

(t, J = 7.2 Hz, 3H); C{ H} NMR (125 MHz, CDCl ): δ 161.9,

64.4−168.8 °C; H NMR (400 MHz, CDCl ): δ 9.78 (d, J = 6.8

154.0, 152.5, 148.9, 147.3, 133.9, 129.9 (d, J = 8.3 Hz, 2C), 129.1,

128.7 (d, J = 11.8 Hz, 2C), 128.6, 128.0, 121.6, 117.5, 116.4, 114.4,

61.6, 13.3; HRMS (ESI) calcd for C H ClN O (M + H)⁺

Hz, 1H), 7.77 (d, J = 8.8 Hz, 1H), 7.61−7.59 (m, 2H), 7.48−7.44 (m,

H), 7.42−7.38 (m, 3H), 7.11 (d, J = 8.0 Hz, 2H), 7.00 (td, J = 6.8,

.8 Hz, 1H), 6.83 (d, J = 8.4 Hz, 2H), 3.36 (q, J = 7.2 Hz, 2H), 2.32

(

404.1160, found 404.1157.

s, 3H), 0.76 (t, J = 7.2 Hz, 3H); C{ H} NMR (100 MHz, CDCl ):

Ethyl 2-((4-Bromophenyl)imino)-2-(2-phenylimidazo[1,2-a]-

δ 162.3, 153.2, 151.9, 147.3, 147.1, 134.3, 134.1, 130.0, 129.3, 128.9,

28.7, 128.2, 127.9, 119.8, 117.3, 116.7, 114.0, 61.2, 20.9, 13.2;

HRMS (ESI) calcd for C H N O (M + H)⁺384.1707, found

pyridin-3-yl)acetate (3ah). Yield 20% (13.4 mg); light yellow solid;

mp: 181.9−184.1 °C; H NMR (400 MHz, CDCl ): δ 9.76 (d, J = 7.2

Hz, 1H), 7.81 (d, J = 8.8 Hz, 1H), 7.60−7.58 (m, 2H), 7.52−7.48 (m,

1H), 7.43−7.40 (m, 5H), 7.07−7.04 (m, 1H), 6.81 (d, J = 8.8 Hz,

2H), 3.36 (q, J = 7.2 Hz, 2H), 0.78 (t, J = 7.2 Hz, 3H); C{ H}

84.1703.

Ethyl-2-((4-methoxyphenyl)imino)-2-(2-phenylimidazo[1,2-a]-

pyridin-3-yl)acetate (3ab). Yield 51% (30.5 mg); light yellow solid;

NMR (125 MHz, CDCl ): δ 161.9, 153.9, 152.5, 148.9, 147.3, 133.8,

H NMR (400 MHz, CDCl ): δ 9.79 (d, J = 7.2 Hz, 1H), 7.82−7.76

131.8, 129.9, 129.1, 128.8, 128.7, 128.1, 121.6, 117.7, 117.4, 116.5,

(

m, 1H), 7.61−7.58 (m, 2H), 7.46−7.43 (m, 1H), 7.40−7.36 (m,

114.4, 61.6, 13.3; HRMS (ESI) calcd for C H BrN O (M + H)

H), 7.03−7.00 (m, 1H), 6.91−6.85 (m, 4H), 3.79 (s, 3H), 3.37 (q, J

448.0655, found 448.0651.

6.8 Hz, 2H), 0.79 (t, J = 7.2 Hz, 3H); C{ H} NMR (100 MHz,

Methyl 2-(2-Phenylimidazo[1,2-a]pyridin-3-yl)-2-(p-tolylimino)-

CDCl ): δ 162.6, 157.2, 153.1, 151.7, 147.1, 143.1, 134.1, 130.0,

acetate (3ai). Yield 71% (39.3 mg); light yellow solid; mp: 171.3−

28.9, 128.7, 128.1, 127.9, 121.2, 117.3, 116.8, 114.1, 114.0, 61.3,

173.2 °C; H NMR (500 MHz, CDCl

): δ 9.79 (d, J = 7.0 Hz, 1H),

5.5, 13.3; HRMS (ESI) calcd for C H N O (M + H) 400.1656,

7.78 (d, J = 8.5 Hz, 1H), 7.60−7.58 (m, 2H), 7.49−7.45 (m, 1H),

7.43−7.39 (m, 3H), 7.13 (d, J = 8.0 Hz, 2H), 7.02 (td, J = 7.0 Hz, J =

1.5 Hz, 1H), 6.84 (d, J = 8.5 Hz, 2H), 2.96 (s, 3H), 2.33 (s, 3H);

found 400.1653.

Ethyl-2-(2-phenylimidazo[1,2-a]pyridin-3-yl)-2-((4-

(

triﬂuoromethoxy)phenyl)imino)acetate (3ac). Yield 41% (27.8

C{ H} NMR (100 MHz, CDCl ): δ 162.9, 153.4, 151.2, 147.1 (d, J

mg); light yellow solid; H NMR (400 MHz, CDCl ): δ 9.77 (d, J

= 5.7 Hz, 2C), 134.5, 134.0, 129.9, 129.6, 128.9, 128.7, 128.3, 128.1,

119.7, 117.4, 116.8, 114.2, 51.6, 21.0; HRMS (ESI) calcd for

7.2 Hz, 1H), 7.82 (d, J = 9.2 Hz, 1H), 7.60−7.57 (m, 2H), 7.54−

.49 (m, 1H), 7.42−7.40 (m, 3H), 7.18 (d, J = 8.0 Hz, 2H), 7.06 (td,

C H N O (M + H) 370.1550, found 370.1562.

J = 7.2, 1.2 Hz, 1H), 6.95−6.91 (m, 2H), 3.36 (q, J = 7.2, 1.2 Hz,

Isopropyl 2-(2-Phenylimidazo[1,2-a]pyridin-3-yl)-2-(p-

H), 0.73 (t, J = 7.2 Hz, 3H); C{ H} NMR (100 MHz, CDCl ): δ

tolylimino)acetate (3aj). Yield 60% (35.7 mg); light yellow solid;

61.7, 154.0, 152.9, 148.5, 147.2, 146.0, 133.7, 129.9, 129.6, 129.0,

28.7, 128.5, 128.3, 127.9, 121.5, 121.0, 117.4, 114.3, 61.4, 13.0;

mp: 173.4−174.7 °C; H NMR (500 MHz, CDCl ): δ 9.77 (d, J = 7.0

Hz, 1H), 7.78 (d, J = 9.5 Hz, 1H), 7.64−7.62 (m, 2H), 7.49−7.45 (m,

1H), 7.42−7.39 (m, 3H), 7.12 (d, J = 8.5 Hz, 2H), 7.02 (td, J = 7.0,

1.0 Hz, 1H), 6.84 (d, J = 8.0 Hz, 2H), 4.19−4.17 (m, 1H), 2.33 (s,

HRMS (ESI) calcd for C H F N O (M + H) 454.1373, found

54.1365.

Ethyl 2-(2-Phenylimidazo[1,2-a]pyridin-3-yl)-2-(m-tolylimino)-

acetate (3ad). Yield 48% (27.6 mg); light yellow solid; mp:

3H), 0.69 (d, J = 6.5 Hz, 6H); C{ H} NMR (125 MHz, CDCl ): δ

161.9, 153.0, 152.3, 147.3, 147.0, 134.2, 134.0, 130.1, 129.3, 128.9,

128.6, 128.1, 120.8, 119.7, 117.3, 116.5, 114.0, 70.3, 20.9, 20.8;

61.4−164.3 °C; H NMR (400 MHz, CDCl ): δ 9.78 (d, J = 5.6

Hz, 1H), 7.78 (d, J = 7.2 Hz, 1H), 7.61 (dd, J = 6.0, 3.2 Hz, 2H),

HRMS (ESI) calcd for C H N O (M + H) 398.1863, found

.48−7.42 (m, 1H), 7.40−7.39 (m, 3H), 7.19 (t, J = 7.6 Hz, 1H),

398.1860.

.02 (t, J = 6.4 Hz, 1H), 6.94 (d, J = 5.6 Hz, 1H), 6.77 (s, 1H), 6.72

tert-Butyl 2-(2-Phenylimidazo[1,2-a]pyridin-3-yl)-2-(p-

tolylimino)acetate (3ak). Yield 47% (29.0 mg); light yellow solid;

(

d, J = 6.4 Hz, 1H), 3.36 (q, J = 6.4 Hz, 2H), 2.32 (s, 3H), 0.75 (t, J =

.6 Hz, 3H); ¹³C{ H} NMR (100 MHz, CDCl ): δ 162.3, 153.4,

mp: 176.5−177.9 °C; H NMR (400 MHz, CDCl

): δ 9.61 (d, J = 7.2

52.0, 149.8, 147.1, 138.6, 134.0, 129.9, 129.0, 128.7, 128.6, 128.3,

28.0, 125.4, 120.6, 117.4, 116.7, 116.6, 114.2, 61.3, 21.4, 13.3;

Hz, 1H), 7.76 (d, J = 8.8 Hz, 1H), 7.67 (dd, J = 8.0, 1.6 Hz, 2H),

7.47−7.34 (m, 4H), 7.13 (d, J = 7.6 Hz, 2H), 6.99−6.96 (m, 1H),

HRMS (ESI) calcd for C H N O (M + H)⁺384.1701, found

6.85 (d, J = 8.0 Hz, 2H), 2.34 (s, 3H), 0.82 (s, 9H); C{ H} NMR

84.1711.

Benzyl 2-(2-Phenylimidazo[1,2-a]pyridin-3-yl)-2-(phenylimino)-

acetate (3ae). Yield 68% (37.6 mg); light yellow solid; mp:

(125 MHz, CDCl ): δ 160.9, 152.9, 152.5, 147.4, 146.9, 134.1, 134.0,

130.3, 129.3, 129.0, 128.4, 128.1, 127.9, 119.6, 117.3, 116.7, 113.9,

84.1, 27.1, 21.0; HRMS (ESI) calcd for C H N O (M + H)

412.2020, found 412.2021.

62.9−164.6 °C; H NMR (400 MHz, CDCl ): δ 9.80 (d, J = 7.2

Hz, 1H), 7.79 (d, J = 8.8 Hz, 1H), 7.62−7.59 (m, 2H), 7.48 (dd, J =

Benzyl 2-(2-Phenylimidazo[1,2-a]pyridin-3-yl)-2-(p-tolylimino)-

1.6, 4.2 Hz, 1H), 7.40−7.38 (m, 3H), 7.31 (t, J = 8.0 Hz, 2H), 7.12

acetate (3al). Yield 61% (40.7 mg); light yellow solid; mp: 161.4−

(t, J = 7.2 Hz, 1H), 7.05−7.01 (m, 1H), 6.93 (d, J = 7.6 Hz, 2H), 3.35

(q, J = 7.2 Hz, 2H), 0.73 (t, J = 7.2 Hz, 3H); C{ H} NMR (100

162.4 °C; H NMR (400 MHz, CDCl

): δ 9.76 (d, J = 6.8 Hz, 1H),

7.77 (d, J = 9.2 Hz, 1H), 7.65−7.62 (m, 2H), 7.47−7.40 (m, 4H),

MHz, CDCl ): δ 162.2, 153.4, 152.1, 149.9, 147.1, 133.9, 129.9,

7.25−7.19 (m, 3H), 7.04 (d, J = 8.4 Hz, 2H), 7.00 (td, J = 6.8, 0.8 Hz,

29.0, 128.8, 128.7, 128.4, 128.0, 124.7, 119.8, 117.4, 116.5, 114.2,

1H), 6.83−6.78 (m, 4H), 4.26 (s, 2H), 2.32 (s, 3H); C{ H} NMR

1.4, 13.2; HRMS (ESI) calcd for C H N O (M + H) 370.1550,

(100 MHz, CDCl ): δ 162.4, 153.3, 151.3, 147.3, 147.1, 134.4, 134.1,

found 370.1554.

134.0, 130.0, 129.5, 129.0, 128.8, 128.7, 128.6, 128.4, 128.4, 128.1,

119.8, 117.3, 116.7, 114.1, 67.3, 21.0; HRMS (ESI) calcd for

Benzyl 2-([1,1′-Biphenyl]-4-ylimino)-2-(2-phenylimidazo[1,2-a]-

pyridin-3-yl)acetate (3af). Yield 66% (44.1 mg); light yellow solid;

C H N O (M + H) 446.1863, found 446.1867.

mp: 141.8−142.9 °C; H NMR (500 MHz, CDCl ): δ 9.81 (d, J = 7.2

2-(2-Phenylimidazo[1,2-a]pyridin-3-yl)-1-(p-tolyl)-2-(p-

Hz, 1H), 7.80 (d, J = 9.2 Hz, 1H), 7.64−7.54 (m, 6H), 7.51−7.47 (m,

tolylimino)ethan-1-one (3am). Yield 30% (19.3 mg); light yellow

H), 7.44−7.39 (m, 5H), 7.33 (t, J = 7.4 Hz, 1H), 7.06−7.00 (m,

solid; mp: 169.2−171.8 °C; H NMR (400 MHz, CDCl ): δ 10.06

H), 3.38 (q, J = 7.2 Hz, 2H), 0.76 (t, J = 7.2 Hz, 3H); C{ H}

(d, J = 6.8 Hz, 1H), 7.78 (d, J = 8.8 Hz, 1H), 7.52−7.48 (m, 1H),

7.24 (d, J = 8.4 Hz, 2H), 7.11−7.06 (m, 4H), 6.99 (t, J = 8.0 Hz, 2H),

6.93 (d, J = 8.0 Hz, 4H), 6.78 (d, J = 8.4 Hz, 2H), 2.29 (s, 3H), 2.18

NMR (100 MHz, CDCl ): δ 162.2, 153.6, 152.1, 149.1, 147.2, 140.7,

37.6, 134.0, 129.9, 129.0, 128.8, 128.6, 128.4, 128.0, 127.5, 127.1,

26.8, 120.4, 117.4, 116.7, 114.2, 61.4, 13.2; HRMS (ESI) calcd for

(s, 3H); C{ H} NMR (100 MHz, CDCl ): δ 192.7, 158.3, 153.7,

C H N O (M + H) 446.1863, found 446.1869.

147.1, 146.3, 144.5, 133.9, 133.4, 132.9, 130.5, 129.9, 129.4, 129.2,

129.1, 128.8, 128.4, 128.2, 127.2, 120.7, 118.0, 117.3, 114.1, 20.8;

Ethyl 2-((4-Chlorophenyl)imino)-2-(2-phenylimidazo[1,2-a]-

pyridin-3-yl)acetate (3ag). Yield 24% (14.5 mg); light yellow solid;

mp: 170.4−173.2 °C; H NMR (500 MHz, CDCl ): δ 9.77 (d, J = 6.8

HRMS (ESI) calcd for C H N O (M + H) 430.1914, found

430.1917.

J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Article

-([1,1′-Biphenyl]-4-yl)-2-(2-phenylimidazo[1,2-a]pyridin-3-yl)-

MHz, CDCl ): δ 162.1, 153.6, 151.6, 147.0, 145.3, 134.7, 133.6,

-(p-tolylimino)-ethan-1-one (3an). Yield 27% (19.9 mg); light

129.8, 129.4, 129.1, 128.1, 126.5, 122.3, 119.8, 117.5, 117.0, 61.4,

yellow solid; mp: 176.1−177.9 °C; H NMR (400 MHz, CDCl ): δ

0.08 (d, J = 6.8 Hz, 1H), 7.79 (d, J = 8.8 Hz, 1H), 7.53 (t, J = 7.2 Hz,

H), 7.46−7.36 (m, 7H), 7.15−7.08 (m, 4H), 7.01−6.93 (m, 4H),

.81 (d, J = 8.0 Hz, 2H), 2.18 (s, 3H); C{ H} NMR (100 MHz,

CDCl ): δ 192.8, 158.1, 153.8, 147.1, 146.3, 146.0, 139.6, 134.0,

33.9, 133.4, 130.6, 129.5, 129.4, 129.3, 129.0, 128.5, 128.4, 128.3,

27.3, 127.2, 126.7, 120.7, 118.0, 117.4, 114.2, 20.8; HRMS (ESI)

calcd for C H N O (M + H) 492.2070, found 492.2074.

29.7, 21.0, 13.2; HRMS (ESI) calcd for C H ClN O (M + H)

24 20

418.1317, found 418.1313.

Ethyl 2-(6-Bromo-2-phenylimidazo[1,2-a]pyridin-3-yl)-2-(p-

tolylimino)acetate (3ha). Yield 43% (29.7 mg); light yellow solid;

mp: 130.4−132.5 °C; H NMR (400 MHz, CDCl ): δ 9.95 (s, 1H),

7.67 (d, J = 9.6 Hz, 1H), 7.59−7.57 (m, 2H), 7.54 (dd, J = 9.2, 1.2

Hz, 1H), 7.40−7.39 (m, 3H), 7.14 (d, J = 8.4 Hz, 2H), 6.85 (d, J =

8.0 Hz, 2H), 3.36 (q, J = 7.2 Hz, 2H), 2.34 (s, 3H), 0.76 (t, J = 7.2

Ethyl 2-(2-(p-Tolyl)imidazo[1,2-a]pyridin-3-yl)-2-(p-tolylimino)-

acetate (3ba). Yield 85% (50.6 mg); light yellow solid; mp:

Hz, 3H); C{ H} NMR (100 MHz, CDCl ): δ 162.1, 153.4, 151.7,

147.1, 145.5, 134.7, 133.6, 131.6, 129.9, 129.4, 129.1, 128.6, 128.1,

119.8, 117.9, 116.9, 108.9, 61.5, 20.9, 13.1; HRMS (ESI) calcd for

39.1−141.4 °C; H NMR (400 MHz, CDCl ): δ 9.77 (d, J = 6.8

Hz, 1H), 7.76 (d, J = 8.8 Hz, 1H), 7.50 (d, J = 8.0 Hz, 2H), 7.44−

C H BrN O (M + H) 462.0812, found 462.0810.

.41 (m, 1H), 7.20 (d, J = 7.6 Hz, 2H), 7.11 (d, J = 8.0 Hz, 2H),

Ethyl 2-(6-Methyl-2-phenylimidazo[1,2-a]pyridin-3-yl)-2-(p-

.00−6.97 (m, 1H), 6.84 (d, J = 8.0 Hz, 2H), 3.40 (q, J = 6.8 Hz,

H), 2.37 (s, 3H), 2.33 (s, 3H), 0.77 (t, J = 7.2 Hz, 3H); C{ H}

NMR (100 MHz, CDCl ): δ 162.4, 153.4, 151.9, 147.4, 147.1, 138.8,

34.2, 131.2, 129.8, 129.3, 128.6, 128.1, 120.7, 119.8, 117.3, 116.6,

13.9, 61.2, 21.4, 20.9, 13.2; HRMS (ESI) calcd for C H N O (M

H) 398.18660, found 398.18630.

tolylimino)acetate (3ia). Yield 78% (46.4 mg); light yellow solid;

mp: 152.4−155.3 °C; H NMR (400 MHz, CDCl ): δ 9.57 (s, 1H),

7.70 (d, J = 8.8 Hz, 1H), 7.60−7.58 (m, 2H), 7.39−7.34 (m, 3H),

7.33 (dd, J = 9.2, 1.6 Hz, 1H), 7.13 (d, J = 8.0 Hz, 2H), 6.85 (d, J =

8.0 Hz, 2H), 3.37 (q, J = 7.2 Hz, 2H), 2.39 (s, 3H), 2.33 (s, 3H), 0.75

(t, J = 7.2 Hz, 3H); C{ H} NMR (100 MHz, CDCl ): δ 162.4,

Ethyl 2-(2-(4-Methoxyphenyl)imidazo[1,2-a]pyridin-3-yl)-2-(p-

153.2, 152.0, 147.5, 146.1, 134.2, 134.1, 131.1, 130.0, 129.3, 128.8,

127.9, 126.4, 124.0, 119.8, 116.6, 116.5, 61.2, 20.9, 18.6, 13.2; HRMS

tolylimino)acetate (3ca). Yield 50% (30.9 mg); light yellow solid;

mp: 141.8−143.6 °C; H NMR (400 MHz, CDCl ): δ 9.76 (d, J = 6.8

(ESI) calcd for C H N O (M + H) 398.18660, found 398.18639.

25 22

Hz, 1H), 7.76 (d, J = 9.2 Hz, 1H), 7.55 (d, J = 8.8 Hz, 2H), 7.46−

Ethyl 2-(7-Methyl-2-phenylimidazo[1,2-a]pyridin-3-yl)-2-(p-

.42 (m, 1H), 7.12 (d, J = 8.0 Hz, 2H), 6.99−6.97 (m, 1H), 6.93 (d, J

tolylimino)acetate (3ja). Yield 80% (47.6 mg); light yellow solid;

8.8 Hz, 2H), 6.84 (d, J = 8.4 Hz, 2H), 3.82 (s, 3H), 3.45 (q, J = 7.2

mp: 166.7−170.1 °C; H NMR (400 MHz, CDCl

): δ 9.66 (d, J = 7.2

Hz, 2H), 2.33 (s, 3H), 0.78 (t, J = 7.2 Hz, 3H); C{ H} NMR (100

Hz, 1H), 7.60−7.57 (m, 2H), 7.52 (s, 1H), 7.41−7.37 (m, 3H), 7.11

MHz, CDCl ): δ 162.4, 160.3, 153.1, 151.9, 147.4, 147.1, 134.2,

(d, J = 8.4 Hz, 2H), 6.84−6.81 (m, 3H), 3.35 (q, J = 7.2 Hz, 2H),

31.3, 129.4, 128.6, 128.1, 126.5, 119.8, 117.2, 116.5, 113.9, 113.5,

2.48 (s, 3H), 2.32 (s, 3H), 0.76 (t, J = 7.2 Hz, 3H); C{ H} NMR

1.3, 55.4, 20.9, 13.3; HRMS (ESI) calcd for C H N O (M + H)

(100 MHz, CDCl

): δ 162.4, 153.4, 151.8, 147.6, 147.5, 139.6, 134.2,

14.1812, found 414.1810.

Ethyl 2-(2-(3,4-Dimethoxyphenyl)imidazo[1,2-a]pyridin-3-yl)-2-

p-tolylimino)acetate (3da). Yield 47% (31.2 mg); light yellow

134.1, 129.9, 129.3, 128.7, 128.0, 127.9, 119.8, 116.5, 116.4, 116.0,

61.2, 21.5, 20.9, 13.2; HRMS (ESI) calcd for C25

398.1863, found 398.1860.

H N O

(M + H)⁺

24 3 2

(

solid; mp: 134.4−136.1 °C; H NMR (500 MHz, CDCl ): δ 9.79 (d,

Ethyl 2-(8-Methyl-2-phenylimidazo[1,2-a]pyridin-3-yl)-2-(p-

J = 7.5 Hz, 1H), 7.78 (d, J = 9.5 Hz, 1H), 7.49−7.45 (m, 1H), 7.19−

.12 (m, 4H), 7.01 (td, J = 7.0 Hz, J = 0.8 Hz, 1H), 6.89 (d, J = 9.0

tolylimino)acetate (3ka). Yield 79% (47.1 mg); light yellow solid;

mp: 128.9−132.7 °C; H NMR (400 MHz, CDCl

): δ 9.65 (d, J = 6.8

Hz, 1H), 6.84 (d, J = 8.5 Hz, 2H), 3.92 (d, J = 11.0 Hz, 6H), 3.47 (d,

Hz, 1H), 7.62−7.59 (m, 2H), 7.41−7.37 (m, 3H), 7.24 (d, J = 6.8 Hz,

1H), 7.11 (d, J = 8.4 Hz, 2H), 6.93 (t, J = 7.2 Hz, 1H), 6.83 (d, J = 8.4

Hz, 2H), 3.33 (q, J = 7.2 Hz, 2H), 2.71 (s, 3H), 2.32 (s, 3H), 0.76 (t,

J = 7.5 Hz, 2H), 2.34 (s, 3H), 0.78 (t, J = 7.0 Hz, 3H); C{ H} NMR

(

125 MHz, CDCl ): δ 162.6, 153.1, 151.8, 149.6, 148.5, 147.3, 147.1,

34.4, 129.4, 128.6, 128.3, 126.7, 122.8, 119.8, 117.2, 116.5, 114.0,

J = 7.2 Hz, 3H); C{ H} NMR (100 MHz, CDCl ): δ 162.4, 152.8,

12.6, 110.5, 61.4, 56.0, 55.9, 21.0, 13.3; HRMS (ESI) calcd for

152.0, 147.4, 147.3, 134.3, 134.1, 130.2, 129.3, 128.7, 127.9, 127.3,

C H N O (M + H) 444.1918, found 444.1919.

127.1, 126.4, 119.8, 117.1, 114.0, 61.1, 21.0, 17.2, 13.2; HRMS (ESI)

Ethyl 2-(2-(4-Fluorophenyl)imidazo[1,2-a]pyridin-3-yl)-2-(p-

calcd for C25

(M + H) 398.1863, found 398.1859.

tolylimino)acetate (3ea). Yield 58% (34.9 mg); light yellow solid;

Ethyl 2-(8-Methyl-2-(p-tolyl)imidazo[1,2-a]pyridin-3-yl)-2-(p-

tolylimino)acetate (3la). Yield 88% (54.3 mg); light yellow solid;

mp: 151.9−155.4 °C; H NMR (400 MHz, CDCl ): δ 9.77 (d, J = 7.2

Hz, 1H), 7.76 (d, J = 8.4 Hz, 1H), 7.59 (dd, J = 8.4, 5.6 Hz, 2H), 7.47

mp: 144.3−145.2 °C; H NMR (400 MHz, CDCl

): δ 9.63 (d, J = 7.2

(

t, J = 7.6 Hz, 1H), 7.13−7.07 (m, 4H), 7.02 (t, J = 6.8 Hz, 1H), 6.83

Hz, 1H), 7.49 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 6.8 Hz, 1H), 7.19 (d, J

= 8.0 Hz, 2H), 7.10 (d, J = 8.0 Hz, 2H), 6.90 (t, J = 7.2 Hz, 1H), 6.83

(d, J = 8.4 Hz, 2H), 3.36 (q, J = 7.2 Hz, 2H), 2.70 (s, 3H), 2.36 (s,

3H), 2.32 (s, 3H), 0.76 (t, J = 7.2 Hz, 3H); C{ H} NMR (100

MHz, CDCl ): δ 162.5, 152.9, 152.1, 147.5, 147.4, 138.6, 134.1,

131.4, 130.0, 129.3, 128.6, 127.2, 127.1, 126.4, 119.8, 117.0, 113.9,

d, J = 8.0 Hz, 2H), 3.45 (q, J = 7.2 Hz, 2H), 2.33 (s, 3H), 0.78 (t, J =

.2 Hz, 3H); ¹³C{ H} NMR (125 MHz, CDCl ): δ 164.3, 162.2 (d, J

258.8 Hz, 2C), 152.0, 151.6, 147.2, 147.0, 134.4, 131.8 (d, J = 8.3

Hz, 2C), 130.1 (d, J = 3.0 Hz, 2C), 129.4, 128.7, 128.4, 119.7, 117.3,

16.7, 115.1 (d, J = 21.5 Hz, 2C), 114.2, 61.4, 21.0, 13.3; HRMS

(

ESI) calcd for C H FN O (M + H) 402.1612, found 402.1608.

61.1, 21.3, 20.9, 17.2, 13.2; HRMS (ESI) calcd for C26

H) 412.2020, found 412.2017.

(M +

Ethyl 2-(2-(4-Chlorophenyl)imidazo[1,2-a]pyridin-3-yl)-2-(p-

tolylimino)acetate (3fa). Yield 40% (25.0 mg); light yellow solid;

Ethyl 2-(2-(4-Fluorophenyl)-6-methylimidazo[1,2-a]pyridin-3-yl)-

mp: 142.6−145.8 °C; H NMR (400 MHz, CDCl ): δ 9.76 (d, J = 6.8

2-(p-tolylimino)-acetate (3ma). Yield 60% (37.3 mg); light yellow

Hz, 1H), 7.76 (d, J = 8.8 Hz, 1H), 7.57−7.49 (m, 3H), 7.39 (d, J =

solid; mp: 167.7−168.9 °C; H NMR (400 MHz, CDCl

): δ 9.54 (s,

.4 Hz, 2H), 7.13 (d, J = 8.0 Hz, 2H), 7.08−7.04 (m, 1H), 6.83 (d, J

1H), 7.70 (d, J = 7.2 Hz, 1H), 7.60−7.56 (m, 2H), 7.34 (dd, J = 7.2,

1.2 Hz, 1H), 7.15−7.07 (m, 5H), 6.84 (d, J = 6.8 Hz, 2H), 3.43 (q, J

= 5.6 Hz, 2H), 2.40 (s, 3H), 2.34 (s, 3H), 0.78 (t, J = 5.6 Hz, 3H);

8.4 Hz, 2H), 3.45 (q, J = 7.2 Hz, 2H), 2.34 (s, 3H), 0.79 (t, J = 7.2

Hz, 3H); C{ H} NMR (100 MHz, CDCl ): δ 162.3, 151.5, 151.1,

47.1, 146.7, 135.4, 134.6, 132.0, 131.3, 129.4, 128.8, 128.7, 128.3,

C{ H} NMR (100 MHz, CDCl ): δ 164.5 (d, J = 246.2 Hz, 2C),

19.7, 117.2, 116.8, 114.5, 61.5, 20.9, 13.3; HRMS (ESI) calcd for

162.4, 147.4, 146.0, 134.3, 131.8 (d, J = 7.9 Hz, 2C), 131.2, 130.3 (d,

J = 2.7 Hz, 2C), 129.3, 126.4, 124.1, 119.7, 116.6, 115.0 (d, J = 21.5

Hz, 2C), 61.3, 20.9, 18.6, 13.2; HRMS (ESI) calcd for C H FN O

C H ClN O (M + H) 418.1317, found 418.1314.

Ethyl 2-(6-Chloro-2-phenylimidazo[1,2-a]pyridin-3-yl)-2-(p-

tolylimino)acetate (3ga). Yield 42% (26.3 mg); light yellow solid;

(M + H) 416.1769, found 416.1765.

mp: 137.0−137.9 °C; H NMR (400 MHz, CDCl ): δ 9.87 (s, 1H),

Ethyl 2-(2-(4-Fluorophenyl)-7-methylimidazo[1,2-a]pyridin-3-yl)-

.72 (d, J = 9.6 Hz, 1H), 7.59−7.57 (m, 3H), 7.44−7.39 (m, 4H),

.14 (d, J = 8.0 Hz, 2H), 6.85 (d, J = 8.0 Hz, 2H), 3.36 (q, J = 7.2 Hz,

H), 2.34 (s, 3H), 0.76 (t, J = 7.2 Hz, 3H); C{ H} NMR (125

2-(p-tolylimino)-acetate (3na). Yield 67% (41.7 mg); light yellow

solid; mp: 165.6−167.7 °C; H NMR (400 MHz, CDCl ): δ 9.64 (d,

J = 5.6 Hz, 1H), 7.59−7.56 (m, 2H), 7.53 (s, 1H), 7.13−7.07 (m,

J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Complete contact information is available at:

Article

H), 6.86−6.81 (m, 3H), 3.43 (q, J = 5.6 Hz, 2H), 2.49 (s, 3H), 2.33

Jiu-Jian Ji − Jiangxi Province Key Laboratory of Synthetic

Chemistry, School of Chemistry, Biology and Materials Science,

East China University of Technology, Nanchang 330013, China

Xiao Zhu − Jiangxi Province Key Laboratory of Synthetic

Chemistry, School of Chemistry, Biology and Materials Science,

East China University of Technology, Nanchang 330013, China

Zong-Bo Xie − Jiangxi Province Key Laboratory of Synthetic

Chemistry, School of Chemistry, Biology and Materials Science,

East China University of Technology, Nanchang 330013, China

(

s, 3H), 0.78 (t, J = 7.0 Hz, 3H); C{ H} NMR (100 MHz, CDCl ):

δ 164.5 (d, J = 246.2 Hz, 2C) 162.5, 152.2, 151.6, 147.5, 147.3, 139.8,

34.5, 131.8 (d, J = 8.5 Hz, 2C), 130.3 (d, J = 2.7 Hz, 2C), 129.3,

27.9, 119.8, 116.6, 116.3, 115.9, 115.0, 114.8, 61.3, 21.5, 20.9, 13.2;

HRMS (ESI) calcd for C H FN O (M + H) 416.1769, found

16.1772.

Ethyl 2-(2-Methylimidazo[1,2-a]pyridin-3-yl)-2-(p-tolylimino)-

acetate (3oa). Yield 50% (24.1 mg); light yellow solid; mp:

28.4−131.1 °C; H NMR (400 MHz, CDCl ): δ 9.81 (d, J = 7.2

Hz, 1H), 7.65 (d, J = 8.8 Hz, 1H), 7.40 (t, J = 8.0 Hz, 1H), 7.14 (d, J

8.0 Hz, 2H), 6.97 (t, J = 7.2 Hz, 1H), 6.88 (d, J = 8.4 Hz, 2H), 4.15

https://pubs.acs.org/10.1021/acs.joc.0c01940

(

q, J = 7.2 Hz, 2H), 2.52 (s, 3H), 2.35 (s, 3H), 1.08 (t, J = 7.2 Hz,

H); ¹³C{ H} NMR (100 MHz, CDCl ): δ 163.7, 151.8, 150.4,

47.2, 147.0, 134.1, 129.3, 129.1, 127.8, 120.1, 116.5, 116.2, 113.7,

1.7, 20.9, 15.4, 13.7; HRMS (ESI) calcd for C H N O (M + H)

22.1550, found 322.1548.

Ethyl 2-(6-Phenylimidazo[2,1-b]thiazol-5-yl)-2-(p-tolylimino)-

acetate (3pa). Yield 58% (33.9 mg); light yellow solid; mp:

Notes

The authors declare no competing ﬁnancial interest.

ACKNOWLEDGMENTS

■

We are grateful to the National Natural Science Foundation of

China (21602027 and 11765002), the Science Foundation for

Excellent Young Scholars of Jiangxi Province

(20202ZDB01003), the Natural Science Foundation of Jiangxi

Province (20202BAB203008), the Postdoctoral Science of

Jiangxi Province (2019KY40 and 2019KY41), and the

Scientiﬁc Research Foundation of East China University of

Technology (DHBK2016112) for ﬁnancial support.

69.3−169.9 °C; H NMR (400 MHz, CDCl ) δ 8.50 (d, J = 4.4

Hz, 1H), 7.56−7.54 (m, 2H), 7.39−7.37 (m, 3H), 7.11 (d, J = 8.0 Hz,

H), 6.94 (d, J = 4.4 Hz, 1H), 6.81 (d, J = 8.0 Hz, 2H), 3.43 (q, J =

.2 Hz, 2H), 2.32 (s, 3H), 0.77 (t, J = 7.2 Hz, 3H); C{ H} NMR

13 1

(

100 MHz, CDCl ): δ 162.4, 153.4, 153.2, 150.6, 147.2, 134.3, 134.0,

29.6, 129.3, 128.8, 128.0, 122.4, 120.0, 119.9, 112.8, 61.3, 20.9, 13.2;

HRMS (ESI) calcd for C H N O S (M + H) 390.1271, found

90.1275.

ASSOCIATED CONTENT

■

REFERENCES

■

sı Supporting Information

The Supporting Information is available free of charge at

https://pubs.acs.org/doi/10.1021/acs.joc.0c01940.

(1) For a book and reviews, see (a) Couty, F.; Evano, G. in

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Accession Codes

CCDC 1951464 contains the supplementary crystallographic

data for this paper. These data can be obtained free of charge

via www.ccdc.cam.ac.uk/data_request/cif, or by emailing

data_request@ccdc.cam.ac.uk, or by contacting The Cam-

bridge Crystallographic Data Centre, 12 Union Road,

Cambridge CB2 1EZ, UK; fax: +44 1223 336033.

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AUTHOR INFORMATION

■

Corresponding Authors

d) Kaminski, J. J.; Doweyko, A. M. Antiulcer Agents. 6. Analysis of

Zhi-Qiang Zhu − Jiangxi Province Key Laboratory of Synthetic

Chemistry, School of Chemistry, Biology and Materials Science,

East China University of Technology, Nanchang 330013,

China; orcid.org/0000-0003-4915-9357 ; Email: zhqzhu@

ecut.edu.cn

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Juan Tang − Ministry of Education Key Laboratory of

Functional Small Organic Molecule, Department of Chemistry

and Chemical Engineering, Jiangxi Normal University,

Nanchang 330022, China; Email: juantang@jxnu.edu.cn

Zhang-Gao Le − Jiangxi Province Key Laboratory of Synthetic

Chemistry, School of Chemistry, Biology and Materials Science,

East China University of Technology, Nanchang 330013,

China; Email: zhgle@ecut.edu.cn

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Authors

Dong Guo − Jiangxi Province Key Laboratory of Synthetic

Chemistry, School of Chemistry, Biology and Materials Science,

East China University of Technology, Nanchang 330013, China

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