Selenium-Catalyzed Oxidative CâH Amination of (E) - ACS Publications

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Selenium-catalyzed oxidative C-H amination of (E)-3(arylamino)-2-styrylquinazolin-4(3H)-ones: a metal-free synthesis of 1,2-diarylpyrazolo[5,1-b]quinazolin-9(1H)-ones Yetong Zhang, Yinlin Shao, Julin Gong, Jianghe Zhu, Tianxing Cheng, and Jiuxi Chen J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b03179 • Publication Date (Web): 11 Feb 2019 Downloaded from http://pubs.acs.org on February 11, 2019

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The Journal of Organic Chemistry

Selenium-catalyzed

oxidative

C−H

amination

(E)-3-(arylamino)-2-styrylquinazolin-4(3H)-ones:

a

of

metal-free

synthesis of 1,2-diarylpyrazolo[5,1-b]quinazolin-9(1H)-ones Yetong Zhang, Yinlin Shao,* Julin Gong, Jianghe Zhu, Tianxing Cheng, and Jiuxi Chen* College of Chemistry & Materials Engineering, Wenzhou University, Wenzhou 325035, China.

O N

R N

Ar NH

O cat. (PhSe)2 Ph

Oxidant metal-f ree

R1

Ar N N

Ph

N 23 examples up to 87% yield

ABSTRACT: A novel metal-free catalysis protocol for the synthesis of 1,2-diarylpyrazolo[5,1-b]quinazolin-9(1H)-ones via intramolecular oxidative C-H amination of (E)-3-(arylamino)-2-styrylquinazolin-4(3H)-ones has been developed with moderate to good yield. The method shows good functional group tolerance. The presented approach offers a new synthetic pathway toward the core structures of 2,3-fused quinazolinones. Moreover, the present synthetic route could be readily scaled up to gram quantity without difficulty. A possible mechanism involves seleniranium ion followed by three-membered ring opening to form C-N bond. _______________________________________________________________________________

INTRODUCTION Among the numerous nitrogen-containing compounds, 2,3-fused quinazolinones with 1

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diverse heterocycles represents an important scaffold ubiquitously found in many natural products, drugs, agrochemicals and other pharmaceutically active ingredients (eg. tryptanthrin and rutaecarpine),1 they are known to exhibit antibiotic, anticancer and antimalarial activities (Fig. 1).2 In view of their importance, a series of methods has been developed for the construction of these 2,3-heterocycles-fused quinazolinones.3 Fig.1 Bioactive 2,3-heterocycle fused quinazolinones CF3

O O

O

N N

N N

N

N N Ph

N

N Anti cancer

PED4 inhibitor

O

O N

COOH

N H

N N

O

OCH3 Antiallergic

combined

Antimicrobial

O

N N

The

N N

F

S

EGFR inhibitor

molecules

of

indazole

and

quinazolinone

frameworks,

indazoloquinazolinone derivatives, are important biological molecules, some of them are potent inhibitors of phosphodiesterase 4 (PDE4)4a and specificity against cancer cells.4b Our group developed three strategies for the construction of the indazolo[3,2-b]quinazolinones

via

copper-catalyzed

coupling

reaction5a-b

or

palladium-catalyzed sequential cyclization/C−H activation cascade reaction.5c Recently,

we

reported

palladium-catalyzed

synthesis

of 2


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indazolo[3,2-b]quinazolinones which were further proved to be potential as a new class of small-molecule blue fluorophores for fluorescent materials involving intramolecular

aerobic

oxidative

2-aryl-3-(arylamino)quinazolinones

(Scheme

C–H 1a).5d

amination

Moreover,

the

of

combined

molecules of pyrazole and quinazolinone skeletons, pyrazolo[5,1-b]quinazolinones, are important biological molecules which exhibit a broad spectrum of activities such as antiallergic,6a antimicrobial activity.6b Traditionally, pyrazolo[5,1-b]quinazolinone structures are constructed by the condensation of isatoic anhydride with pyrazolone, which is limited in scope and inconvenient operation.6 Wang group reported transition-metal catalyzed

synthesis of pyrazolo[5,1-b]quinazolinone derivatives.7

Although the transition-metal-catalyzed strategies that have shown high efficiency, metal-free protocols are also desirable due to their advantages with regard to purity requirements in biological and medicinal research.8 Organoselenium catalysis is an important and unique subject that presents additional opportunities to develop novel green synthetic methods with industrial potential compared with transition metals.9 Also selenium is much less expensive than noble metals, and the organoselenium catalysts are sufficiently robust to be recycled and reused with little deactivation.10 Recently, organoselenium catalysts have been successfully employed in a series of useful transformations.11 Since Breder’s pioneering contributions to the direct oxidative vinylic amination of alkenes by selenium catalysis,12 remarkable advances in selenium-catalyzed C=C functionalization have been documented. In continuation of our interest on N-heterocycles synthesis,13 we herein report the first example of 3



Page 4 of 42

metal-free method for the synthesis of pyrazolo[5,1-b]quinazolinones through selenium-catalyzed

oxidative

C−H

amination

of

easily

available

(E)-3-(arylamino)-2-styrylquinazolin-4(3H)-ones (Scheme 1b). Scheme 1. The new strategy for the synthesis of pyrazolo[5,1-b]quinazolinones

a) Pd-catalyzed synthesis of indazolo[3,2-b]quinazolinones O R

Ar NH N H

N

O [Pd] R1

ref. 5d Our previous work

R

Ar N N

R1

N

b) Selenium-catalyzed synthesis of pyrazolo[5,1-b]quinazolinones (This work) O N

R

O

Ar NH

N

cat. (PhSe)2 Oxidant metal-free

Ph

R1

Ar N N

Ph

N

RESULTS AND DISCUSSION At

the

outset

of

our

studies,

we

used

(E)-3-(phenylamino)-2-styrylquinazolin-4(3H)-one (1a) as the test substrate to determine optimal conditions for the title reaction. In initial experiments 1a was reacted with 2 equivalent of N-Fluorobenzenesulfonimide (NFSI) in the presence of various catalysts in toluene at 110 oC for 48 h. The reaction did not work in the absence of any catalyst (Table 1, entry 1). However, diphenyl diselane as a catalyst provided access to target structure 1,2-diphenylpyrazolo[5,1-b]quinazolin-9(1H)-one (2a) in 49% yield (Table 1, entry 2), while 1,2-dibenzyldisulfane (DBDS) furnished the oxidative amination product 2a only in 17% (Table 1, entry 3). Replacement of 4


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diphenyl diselane with other common transition metal catalysts, such as PdCl2 or FeCl3, was ineffective (Table 1, entries 4−5). A survey of solvent revealed that acetonitrile was optimal to give a best 79% yield, and the use of dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), xylene and pyridine led to lower yields (Table 1, entries 6−10). Encouraged by the promising result, we further examined the reaction temperature and found 90 oC was enough for such oxidative/cyclization process (Table 1, entries 11−12). The yield of the desired product decreased when the reaction time was shortened to 24 h (Table 1, entry 11). The classical oxidants such as K2S2O8, 2,3-dicyano-5,6-dichlorobenzoquinone (DDQ) and Cu(OAc)2 diminished the yield of 2a sharply (Table 1, entries 13−15). The yield decreased to some extent by either removing 4 Å molecular sieves from the reaction medium or decreasing the amount of oxidant to 1.0 equivalent (Table 1, entries 16-17). Therefore, the optimal reaction conditions can be summarized as follows: 0.2 mmol substrate in acetonitrile (5 mL) with PhSeSePh catalyst (5 mol %), NFSI (2 equiv) and 4 Å molecular sieves 0.06 g at 90 °C for 48 h under air atmosphere. The structure of 2a was further confirmed by X-ray diffraction analysis (Fig. 2)14. Fig.2 X-ray crystal structure of product 2a.

5



Page 6 of 42

Table 1. Optimization of reaction conditionsa O N

H N

O catalyst, oxidant

Ph

solvent

Ph

N

Ph N N

Ph

N

1a

2a

catalyst

oxidant

temp. (oC)

solvent

1

-

NFSI

110

Toluene

trace

2

(PhSe)2

NFSI

110

Toluene

49

3

DBDS

NFSI

110

Toluene

17

4

PdCl2

NFSI

110

Toluene

trace

5

FeCl3

NFSI

110

Toluene

trace

6

(PhSe)2

NFSI

110

DMF

41

7

(PhSe)2

NFSI

110

DMSO

14

8

(PhSe)2

NFSI

110

xylene

49

9

(PhSe)2

NFSI

110

Pyridine

trace

10

(PhSe)2

NFSI

110

CH3CN

79

11

(PhSe)2

NFSI

90

CH3CN

79(70)c

12

(PhSe)2

NFSI

70

CH3CN

65

13

(PhSe)2

K2S2O8

90

CH3CN

5

14

(PhSe)2

DDQ

90

CH3CN

35

15

(PhSe)2

Cu(OAc)2

90

CH3CN

4

16d

(PhSe)2

NFSI

90

CH3CN

65

e

(PhSe)2

NFSI

90

CH3CN

70

entry

17

yield (%)b

a

Conditions: 1a (0.2 mmol), catalyst (5 mol%), oxidant (2 equiv), solvent (5 mL), 4A MS (0.06 g), 90 oC, 48 h. bIsolated yield. c24 h. d 1.0 eq.NFSI was used. e without 4A MS.

With optimized conditions in hand, investigations continued with the exploration of the scope of our oxidative amination/cyclization protocol for the construction of pyrazolo[5,1-b]quinazolinones (Table 2). A variety of substituents (R1, R2, R3) in compound 1 were tested and delivered to product 2 in uniformly high efficiency. First,

the

variation

of

the

R1

group

of 6


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(E)-3-(phenylamino)-2-styrylquinazolin-4(3H)-ones 1 was investigated. The results showed that both electron-donating and electron-withdrawing substituents were well-tolerated and provided the corresponding products in moderate to good yields. For example, substrates bearing a methyl group afforded the cyclized products 2b, 2c and 2d in 80-85% yield, respectively (Table 2, entries 1-3). Substrate (E)-7,8-dimethyl-3-(phenylamino)-2-styrylquinazolin-4(3H)-one

afforded

the

corresponding desired product 2e in 82% yield similarly (Table 2, entry 4). Electron-donating group such as -OMe at the 6 position of the aryl ring in quinazolinone furnished product 2f in 87% yield. To our delight, the method tolerates the entire range of halogen substituents and strong electron-withdrawing substituent (e.g., -CF3), although the yield of cyclized products 2g-2n were slight lower than those of electron-sufficient substrates, which makes this method particularly appealing, enabling further access to more complex compounds in combination with cross-coupling transformations (Table 2, entries 6−13). We next examined the substitution effect of R2 on the aromatic ring of (E)-3-(phenylamino)-2-styrylquinazolin-4(3H)-ones. Substrates bearing an o-, m- or p-methyl substituent attaching to the amino group were evaluated, affording 2o-2q in 67-82% yield respectively (Table 2, entries 14−16). The lower yield of 2o may arise from the steric hindrance. The electronic property of the substituents is not critical for this transformation. In general, the substrates bearing an electron-donating substituent (eg.

−OMe)

provided

a

slightly

higher

yield

than

those

bearing

an

electron-withdrawing substituent e.g. −F, −Cl and −CF3 (Table 2, entries 17−22). 7



Page 8 of 42

Encouraged by the promising result, we further examined the variation of aryl group in styrene motif of (E)-3-(phenylamino)-2-styrylquinazolin-4(3H)-ones (Table 2, entries 23−25). It is obvious that electron-withdrawing groups decreased the cyclization yield to some extent, probably due to the decreasing activity to form active electrophilic additional intermediate with Se species. Alkyl substituents such as isopropyl on the nitrogen atom was also fine compatible with this intramolecular oxidative amination cyclization reaction (Table 2, entries 26). Table 2. Synthesis of 1,2-diarylpyrazolo[5,1-b]quinazolin-9(1H)-onesa

8


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R2 N

R1

NH

PhSeSePh, NFSI o

N

MS 4A, MeCN, 90 C, 48 h

R3

N 2

(1)

(2)

(3)

N N

N

2c, 83%

2d, 80%

F

F

2h, 65%

O Br

N N

N

N

2l 78%

2m, 71%

(15) O

(19)

N N

(21)

CF3

(22) O

N N

N

N 2w, 62%

2v, 65% (25)

N

2t, 70%

2u, 66%

(23)

(24) O

O

O

N N

N N

N 2s, 55%

F

O

N N

N

Cl

(20)

Cl

O

Cl

N N

N 2q, 80%

2p, 82%

(18) O

2r, 85%

N N

N

2o, 67%

N

O

N N

N

O

(16)

O

N N

N N

2n, 60% OCH3

N N

N

(14)

N

O I

N N

2k, 69%

Cl

2j, 70%

O

2i, 71% (12)

O

(13)

N

(11)

N N N

N N

N

2g, 70% (10)

O

O

N N

N

2f, 87%

F3C

(8) Cl

O N N

N (9)

2e, 82%

(7) O

N N

N

N

(6) O

N N

N N

N

2b, 85% (5)

O

O

N N

(17)

(4)

O

O

Cl

R3

N N

R1

o

1

H3CO

R2

O

O

N N N 2x, 85 %

F N N

OCH3

N

F

2y, 29 %

(26) O O

N N

N N N

Cl Cl

2z, trace a

N

2za, 79 %

Conditions: 1 (0.2 mmol), (PhSe)2 (5 mol %), NFSI (2 equiv), CH3CN (5 mL), MS 4A (0.06 g), 90 oC, 48 h, isolated yield.

9



Page 10 of 42

The present synthetic route to pyrazolo[5,1-b]quinazolinone derivatives could be readily scaled up to gram quantity without difficulty. For instance, the reaction at the 3 mmol scale afforded the corresponding product 2a in 78% isolated yield. In addition, N-methylation of 2a gave pyrazolo[5,1-b]quinazolin-4-ium iodide 3a in 95% yield (Scheme 2). Furthermore, the structure of 3a was confirmed by X-ray diffraction analysis (Fig. 3).14

Scheme 2 Gram-scale synthesis of 2a and subsequent methylation

O N N

NH

PhSeSePh (5 mol%) NFSI (2 eq), MS 4Å MeCN, 90 oC, 36 h 78% yield Ph

3 mmol, 1.017g

O

O N N N

Ph

CH3I (12.5 equiv) THF, 70 oC, 24 h 95% yield

0.789 g

N N

Ph

N I CH3 3a

Fig. 3 X-ray crystal structure of product 3a.

Scheme 3 Control experiments

10


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O N

PhSeSePh (5 mol%)

NH

O N N

o

MS 4A, MeCN, 90 oC, 48 h

N

N 1a

(a)

2a

O O N

N

+ PhSeSePh (1 equiv)

N

N

NFSI (2 equiv) o

MS 4A, MeCN, 90 oC, 48 h 50% yield

4a

N (b)

N Se 5a

To gain insight into the diphenyl diselane-catalyzed oxidative amination cyclization reaction mechanism, further experiments were performed (Scheme 3). Our initial attempts to perform the reaction in the absence of NFSI failed to give the desired product 2a (Scheme 3a). However, (Z)-3-(Methyl(phenyl)amino)-2-(2-phenyl-1(phenylselanyl)vinyl)-quinazolin-4(3H)-one (5a) was obtained in 50% yield when (E)-3-(methyl(phenyl)amino)-2-styrylquinazolin-4(3H)-one (4a)

was reacted with

stoichiometric PhSeSePh under standard conditions (Scheme 3b), indicating that an intermolecular electrophilic addition of Se species with C=C bonds may occur in this catalytic transformation. A plausible mechanism for this diphenyl diselane-catalyzed oxidative amination cyclization reaction is shown in Scheme 4. First, NFSI undergoes nucleophilic attack by diphenyl diselane leading to cationic species I. Subsequent electrophilic addition to the C=C double of 1 gives rise to seleniranium ion II, and then intramolecular attack of the amino group leads to three-membered ring opening to yield intermediate III. Which in turn undergoes elimination of HF and HN(SO2Ph)2 together with removal of the catalyst to complete the catalytic cycle. 11



Page 12 of 42

Scheme 4 Proposed mechanism. NFSI

HF + HN(SO2Ph)2 + 2a O

Ph N N

PhSeSePh

Ph

N

Se FPh Ph Se N(SO Ph) 2 2 III

Ph O N N

Se

Se

Ph

F N(SO2Ph)2 I

NHPh

Ph F Se Ph Ph Se N(SO Ph) 2 2 II

1a

CONCLUSIONS In summary, we have developed a new approach for the synthesis of 1,2-diarylpyrazolo[5,1-b]quinazolin-9(1H)-ones by the diphenyl diselane-catalyzed intramolecular

oxidative

amination

cyclization

reaction

of

(E)-3-(phenylamino)-2-styrylquinazolin-4(3H)-ones. This protocol provides an alternative synthetic pathway to access 2,3-heterocycles-fused quinazolinones. Further studies on the other bioactivities of the pyrazolo[5,1-b]quinazolinones and the construction of other useful N-heterocycles are underway in our laboratory.

EXPERIMENTAL SECTION General Methods. Melting points are uncorrected. 1H NMR and 13C NMR spectra were measured on a 500 MHz spectrometer (1H at 500 MHz, 13C at 125 MHz), using CDCl3 and d6-DMSO as the solvent at room temperature. Chemical shifts are given δ 12


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relative to TMS, and the coupling constants J are given in hertz. High-resolution mass spectra

were

recorded

on

an

ESI-Q-TOF

mass

spectrometer.

All

(E)-3-(phenylamino)-2-styrylquinazolin-4(3H)-one substrates (1a-1w) were prepared by the modified literature methods.15 Other commercially obtained reagents were used without further puriﬁcation. Column chromatography was performed using EM silica gel 60 (300−400 mesh). X-ray crystallographic analysis was done at the X-ray crystallography facility, Shanghai Institute of Organic Chemistry (SIOC), Chinese Academy of Sciences (CAS). General

procedure

for

the

Synthesis

of

1,2-diphenylpyrazolo[5,1-b]quinazolin-9(1H)-ones. To a Schlenk tube were added (E)-3-(phenylamino)-2-styrylquinazolin-4(3H)-one 1 (0.2 mmol), (PhSe)2 (0.01 mmol), NFSI (0.4 mmol), MS 4Å (60 mg) and MeCN (5 mL) under air. The tube was tightly capped and stirred for 10 minutes at room temperature for proper mixing of the reactants, and then heated at 90 °C with vigorous stirring for 48 hours. Then the mixture was poured into 10 mL water, extracted with ethyl acetate (10 mL X 3), the combined organic layers were dried over anhydrous Na2SO4 and filtrated. The solvent was evaporated under vacuum and the residue was purified by flash column chromatography with petroleum ether/ethyl acetate (4:1) to afford the desired products. (E)-3-(Phenylamino)-2-styrylquinazolin-4(3H)-one (1a): white solid (2.7 g, 80%). 1H

NMR (500 MHz, DMSO-d6) δ 9.23 (s, 1H), 8.12-8.05 (m, 2H), 7.91-7.80 (m, 2H),

7.63 (d, J = 6.5 Hz, 2H), 7.55-7.40 (m, 5H), 7.21 (t, J = 7.5 Hz, 2H), 6.86 (t, J = 7.0 13



Page 14 of 42

Hz, 1H), 6.71 (d, J = 8.0 Hz, 2H); 13C{1H} NMR (125 MHz, CDCl3) δ 160.1, 154.0, 147.2, 146.8, 140.3, 135.0, 134.9, 129.8, 129.2, 129.0, 127.7, 127.4, 126.5, 126.3, 121.1, 120.5, 118.2, 112.8. HRMS (ESI) calcd for C22H18N3O1 [M+H]+: 340.1450, found 340.1454. (E)-5-Methyl-3-(phenylamino)-2-styrylquinazolin-4(3H)-one (1b): white solid (1.50 g, 85%). IR (KBr) v (cm-1): 3267, 3022, 2972, 1658, 1633, 1599, 1551, 1494, 1475, 1447, 1354, 811, 755, 698. 1H NMR (500 MHz, DMSO-d6) δ 9.11 (s, 1H), 8.04 (d, J = 16 Hz, 1H), 7.71 (s, 1H), 7.62 (d, J = 8.0 Hz, 3H), 7.44-7.39 (m, 4H), 7.28 (d, J = 7.5 Hz, 1H), 7.20 (t, J = 8.0 Hz, 2H), 6.85 (s, 1H), 6.71 (d, J = 8.0 Hz, 2H), 2.73 (s, 3H);

13C{1H}

NMR (125 MHz, CDCl3) δ 161.7, 153.1, 149.0, 146.9, 141.5, 141.4,

135.8, 134.0, 129.8, 129.7, 129.2, 128.9, 128.2, 126.1, 122.9, 119.7, 118.4, 114.7, 22.9. HRMS (ESI) calcd for C23H20N3O1 [M+H]+: 354.1601, found 354.1609. (E)-6-Methyl-3-(phenylamino)-2-styrylquinazolin-4(3H)-one (1c): white solid (1.50 g, 85%). IR (KBr) v (cm-1): 3257, 3040, 2982, 1660, 1626, 1597, 1545, 1489, 1444, 1358, 1342, 827, 774, 692. 1H NMR (500 MHz, DMSO-d6) δ 9.23 (s, 1H), 8.02 (d, J = 16 Hz, 1H), 7.90 (s, 1H), 7.71 (s, 2H), 7.62-7.61 (m, 2H), 7.47-7.37 (m, 4H), 7.21-7.18 (m, 2H), 6.85 (t, J = 7.5 Hz, 1H), 6.68 (d, J = 8.0 Hz, 2H), 2.46 (s, 3H); 13C{1H}

NMR (125 MHz, CDCl3) δ 160.4, 151.7, 145.7, 144.6, 140.1, 135.9, 135.5,

134.8, 128.8, 128.6, 127.9, 127.2, 126.6, 125.5, 122.0, 119.9, 117.3, 113.8, 20.5. HRMS (ESI) calcd for C23H20N3O1 [M+H]+: 354.1601, found 354.1603. (E)-7,8-Dimethyl-3-(phenylamino)-2-styrylquinazolin-4(3H)-one (1e): white solid (1.56 g, 85%). IR (KBr) v (cm-1): 3254, 3056, 1661, 1629, 1603, 1550, 1495, 1447, 14


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1360, 1339, 783, 755, 691. 1H NMR (500 MHz, CDCl3) δ 8.20 (d, J = 15.5 Hz, 1H), 7.98 (d, J = 8.0 Hz, 1H), 7.60-7.55 (m, 3H), 7.38-7.34 (m, 3H), 7.26-7.22 (m, 4H), 6.98 (t, J = 7.5 Hz, 1H), 6.80 (d, J = 8.0 Hz, 2H), 2.71 (s, 3H), 2.46 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 161.5, 151.6, 146.7, 145.4, 143.8, 141.0, 135.8, 134.1, 129.6, 129.4, 128.8, 128.6, 128.1, 123.8, 122.7, 119.0, 118.5, 114.6, 21.0, 13.2. HRMS (ESI) calcd for C24H22N3O1 [M+H]+: 368.1763, found 368.1763. (E)-6-Methoxy-3-(phenylamino)-2-styrylquinazolin-4(3H)-one (1f): white solid (1.48 g, 80%). IR (KBr) v (cm-1): 3268, 3024, 2976, 1662, 1632, 1599, 1549, 1491, 1439, 1339, 822, 769, 690. 1H NMR (500 MHz, DMSO-d6) δ 9.22 (s, 1H), 7.99 (d, J = 16.0 Hz, 1H), 7.76 (d, J = 8.5 Hz, 1H), 7.60 (d, J = 7.0 Hz, 2H), 7.51-7.37 (m, 6H), 7.20 (t, J = 8.0 Hz, 2H), 6.85 (t, J = 7.5 Hz, 1H), 6.69 (d, J = 8.0 Hz, 2H), 3.88 (s, 3H);

13C{1H}

NMR (125 MHz, CDCl3) δ 161.3, 158.3, 151.3, 146.7, 142.3, 140.6,

135.9, 129.7, 129.6, 129.5, 128.9, 128.1, 125.4, 123.0, 121.9, 118.3, 114.8, 106.3, 56.0. HRMS (ESI) calcd for C23H20N3O2 [M+H]+: 370.1566, found 370.1560. (E)-6-Fluoro-3-(phenylamino)-2-styrylquinazolin-4(3H)-one (1g): white solid (1.55 g, 87%). IR (KBr) v (cm-1): 3261, 3039, 1660, 1628, 1602, 1548, 1483, 1445, 1344, 832, 777, 690. 1H NMR (500 MHz, DMSO-d6) δ 9.24 (s, 1H), 8.05 (d, J = 16.0 Hz, 1H), 7.87 (d, J = 5.0 Hz, 1H), 7.80-7.77 (m, 2H), 7.63-7.61 (m, 2H), 7.47-7.39 (m, 4H), 7.22-7.19 (m, 2H), 6.87 (d, J = 7.5 Hz, 1H), 6.72 (d, J = 8.0 Hz, 2H); 13C{1H} NMR (125 MHz, CDCl3) δ 161.7, 152.8, 146.4, 144.3, 141.7, 135.6, 130.3 (d, J = 8.3 Hz), 130.0, 129.7, 129.0, 128.3, 123.6 (d, J = 24.2 Hz), 123.2, 117.9, 114.8, 111.9 (d, J = 23.8 Hz). HRMS (ESI) calcd for C22H17F1N3O1 [M+H]+: 358.1356, found 15



Page 16 of 42

358.1360. (E)-7-Fluoro-3-(phenylamino)-2-styrylquinazolin-4(3H)-one (1h): white solid (1.52 g, 85%). IR (KBr) v (cm-1): 3263, 3042, 1667, 1619, 1579, 1546, 1476, 1443, 1344, 867, 774, 699. 1H NMR (500 MHz, DMSO-d6) δ 9.24 (s, 1H), 8.18-8.15 (m 1H), 8.08 (d, J = 16.0 Hz, 1H), 7.64-7.56 (m, 3H), 7.48-7.38 (m, 5H), 7.21 (t, J = 8.0 Hz, 2H), 6.86 (t, J = 7.5 Hz, 1H), 6.72 (d, J = 8.5 Hz, 2H); 13C{1H} NMR (125 MHz, CDCl3) δ 160.7, 154.7, 146.5, 142.6, 135.5, 130.2, 129.7, 129.7, 129.0, 128.4, 123.5, 117.9, 116.5, 115.4 (d, J = 23.8 Hz), 114.8, 112.9 (d, J = 21.8 Hz).

HRMS (ESI) calcd for

C22H17F1N3O1 [M+H]+: 358.1356, found 358.1361. (E)-5-Chloro-3-(phenylamino)-2-styrylquinazolin-4(3H)-one (1i): white solid (1.62 g, 87%). IR (KBr) v (cm-1): 3268, 3055, 1672, 1628, 1581, 1542, 1496, 1450, 1346, 814, 753, 693. 1H NMR (500 MHz, DMSO-d6) δ 9.24 (s, 1H), 8.11-8.06 (m, 2H), 7.86 (d, J = 2.0 Hz, 1H), 7.64-7.62 (m, 2H), 7.57-7.55 (m, 1H), 7.48-7.40 (m, 4H), 7.21 (t, J = 8.0 Hz, 2H), 6.86 (t, J = 7.5 Hz, 1H), 6.72 (d, J = 8.0 Hz, 2H); 13C{1H} NMR (125 MHz, CDCl3) δ 160.9, 154.7, 148.5, 146.4, 142.6, 141.2, 135.5, 130.2, 129.7, 129.0, 128.5, 128.4, 127.3, 127.1, 123.2, 119.5, 117.8, 114.8. HRMS (ESI) calcd for C22H17Cl1N3O1 [M+H]+: 374.1060, found 374.1066. (E)-6-Chloro-3-(phenylamino)-2-styrylquinazolin-4(3H)-one (1j): white solid (1.48 g, 88%). IR (KBr) v (cm-1): 3265, 3032, 1678, 1635, 1604, 1542, 1496, 1471, 1335, 831, 754, 669. 1H NMR (500 MHz, DMSO-d6) δ 9.27 (s, 1H), 8.09-8.04 (m, 2H), 7.93-7.90 (m, 1H), 7.82 (d, J = 9.0 Hz, 1H), 7.64-7.62 (m, 2H), 7.47-7.39 (m, 4H), 7.21 (t, J = 8.0 Hz, 2H), 6.86 (t, J = 7.5 Hz, 1H), 6.72 (d, J = 8.5 Hz, 2H); 13C{1H} 16


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NMR (125 MHz, CDCl3) δ 160.5, 153.7, 146.3, 146.1, 142.2, 135.6, 135.4, 132.3, 130.1, 129.7, 129.5, 129.0, 128.3, 126.4, 123.2, 122.1, 117.9, 114.8. HRMS (ESI) calcd for C22H17Cl1N3O1 [M+H]+: 374.1060, found 374.1069. (E)-6-Bromo-3-(phenylamino)-2-styrylquinazolin-4(3H)-one (1l): white solid (1.81 g, 87%). IR (KBr) v (cm-1): 3266, 3030, 1676, 1635, 1601, 1541, 1496, 1468, 1333, 829, 751, 691. 1H NMR (500 MHz, DMSO-d6) δ 9.25 (s, 1H), 8.18 (d, J = 2.0 Hz, 1H), 8.09-8.01 (m, 2H), 7.75 (d, J = 9.0 Hz, 1H), 7.63-7.62 (m, 2H), 7.47-7.40 (m, 4H), 7.20 (t, J = 8.0 Hz, 2H), 6.86 (t, J = 7.5 Hz, 1H), 6.72 (d, J = 8.0 Hz, 2H); 13C{1H}

NMR (125 MHz, CDCl3) δ 160.3, 153.9, 146.4, 146.3, 142.3, 138.1, 135.5,

130.1, 129.7, 129.6, 129.6, 129.0, 128.3, 123.2, 122.4, 120.0, 117.9, 114.8. HRMS (ESI) calcd for C22H17Br1N3O1 [M+H]+: 418.0555, found 418.0557. (E)-6-Iodo-3-(phenylamino)-2-styrylquinazolin-4(3H)-one (1m): white solid (1.97 g, 85%). IR (KBr) v (cm-1): 3263, 3059, 1671, 1629, 1602, 1541, 1495, 1464, 1331, 830, 756, 691. 1H NMR (500 MHz, DMSO-d6) δ 9.25 (s, 1H), 8.37 (d, J = 2.0 Hz, 1H), 8.17-8.06 (m, 2H), 7.63-7.58 (m, 3H), 7.46-7.40 (m, 4H), 7.20 (t, J = 8.0 Hz, 2H), 6.86 (t, J = 7.5 Hz, 1H), 6.71 (d, J = 8.0 Hz, 2H);

13C{1H}

NMR (125 MHz,

CDCl3) δ 160.1, 154.1, 146.3, 143.7, 142.4, 135.9, 135.5, 130.2, 129.7, 129.6, 129.0, 128.3, 123.2, 122.7, 117.9, 114.8, 100.1. HRMS (ESI) calcd for C22H17I1N3O1 [M+H]+: 466.0416, found 466.0410. (E)-3-(Phenylamino)-2-styryl-6-(trifluoromethyl)quinazolin-4(3H)-one (1n): white solid (1.63 g, 80%). IR (KBr) v (cm-1): 3274, 3042, 1677, 1629, 1603, 1546, 1495, 1451, 1299, 846, 761, 691. 1H NMR (500 MHz, CDCl3) δ 8.50 (s, 1H), 8.25 (d, J = 17



Page 18 of 42

16.0 Hz, 1H), 7.97-7.88 (m, 2H), 7.60-7.57 (m, 3H), 7.39-7.34 (m, 4H), 7.26-7.24 (m, 2H), 7.01 (t, J = 7.5 Hz, 1H), 6.82 (d, J = 8.0 Hz, 2H);

13C{1H}

NMR (125 MHz,

CDCl3) δ 160.7, 155.4, 149.5, 146.1, 143.2, 135.2, 130.9, 130.3, 129.6, 128.9, 128.6, 128.1 (d, J = 33.5 Hz), 124.9, 124.9 (d, J = 4.1 Hz), 123.7 (d, J = 272.3 Hz), 123.1, 120.7, 117.5, 114.7. HRMS (ESI) calcd for C23H17F3N3O1 [M+H]+: 408.1324, found 408.1322. (E)-2-Styryl-3-(o-tolylamino)quinazolin-4(3H)-one (1o): white solid (1.41 g, 80%). IR (KBr) v (cm-1): 3333, 3071, 1683, 1634, 1608, 1548, 1471, 1449, 1339, 820, 755, 698. 1H NMR (500 MHz, DMSO-d6) δ 8.53 (s, 1H), 8.12-8.06 (m, 2H), 7.90 (t, J = 8.0 Hz, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.63 (d, J = 6.5 Hz, 2H), 7.54 (t, J = 7.5 Hz, 1H), 7.48 (d, J = 16.0 Hz, 1H), 7.43-7.39 (m, 3H), 7.17 (d, J = 7.5 Hz, 1H), 6.95 (t, J = 8.0 Hz, 1H), 6.79 (t, J = 7.5 Hz, 1H), 6.20 (d, J = 8.0 Hz, 1H), 2.41 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 160.1, 154.1, 146.3, 143.7, 142.4, 135.9, 135.5, 130.2, 129.7, 129.6, 129.0, 128.3, 123.2, 122.7, 117.9, 114.8, 100.1. HRMS (ESI) calcd for C23H20N3O1 [M+H]+: 354.1606, found 354.1600. (E)-2-Styryl-3-(m-tolylamino)quinazolin-4(3H)-one (1p): white solid (1.46 g, 83%). IR (KBr) v (cm-1): 3243, 3078, 1658, 1631, 1609, 1548, 1468, 1448, 1341, 823, 779, 693. 1H NMR (500 MHz, DMSO-d6) δ 9.13 (s, 1H), 8.12-8.05 (dd, 2H), 7.89 (t, J = 8.0 Hz, 1H), 7.80 (d, J = 8.0 Hz, 1H), 7.63 (d, J = 8.0 Hz, 2H), 7.53 (t, J = 7.5 Hz, 1H), 7.48-7.39 (m, 4H), 7.08 (t, J = 8.0 Hz, 1H), 6.67 (d, J = 7.5 Hz, 1H), 6.54 (s, 1H), 6.48 (d, J = 8.0 Hz, 1H), 2.20 (s, 3H);

13C{1H}

NMR (125 MHz, CDCl3) δ

160.1, 154.1, 146.3, 143.7, 142.4, 135.9, 135.5, 130.2, 129.7, 129.6, 129.0, 128.3, 18


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123.2, 122.7, 117.9, 114.8, 100.1. HRMS (ESI) calcd for C23H20N3O1 [M+H]+: 354.1606, found 354.1599. (E)-2-Styryl-3-(p-tolylamino)quinazolin-4(3H)-one (1q): white solid (1.43 g, 82%). IR (KBr) v (cm-1): 3253, 3026, 1682, 1634, 1609, 1546, 1467, 1448, 1339, 873, 786, 695. 1H NMR (500 MHz, CDCl3) δ 8.23-8.15 (m, 2H), 7.80-7.79 (m, 2H), 7.60-7.57 (m, 3H), 7.46-7.43 (m, 1H), 7.36 (d, J = 8.0 Hz, 3H), 7.15 (s, 1H), 7.05 (d, J = 8.5 Hz, 2H), 6.73 (d, J = 8.5 Hz, 2H), 2.25 (s, 3H);

13C{1H}


161.4, 153.5, 147.6, 144.2, 141.6, 135.7, 134.9, 132.6, 130.2, 129.9, 129.0, 128.3, 127.8, 127.1, 126.5, 121.2, 118.4, 115.0, 20.8. HRMS (ESI) calcd for C23H20N3O1 [M+H]+: 354.1606, found 354.1611. (E)-3-((4-Methoxyphenyl)amino)-2-styrylquinazolin-4(3H)-one (1r): white solid (1.57 g, 85%). IR (KBr) v (cm-1): 3253, 3026, 2832, 1678, 1631, 1605, 1545, 1469, 1448, 1332, 823, 758, 698. 1H NMR (500 MHz, CDCl3) δ 8.24-8.16 (m, 2H), 7.82-7.77 (m, 2H), 7.63-7.59 (m, 3H), 7.45-7.42 (m, 1H), 7.39-7.35 (m, 3H), 7.21 (s, 1H), 6.82-6.78 (m, 4H), 3.72 (s, 3H);

13C{1H}

NMR (125 MHz, CDCl3) δ 161.3,

155.8, 153.3, 147.4, 141.4, 139.8, 135.6, 134.7, 129.8, 128.8, 128.1, 127.6, 126.9, 126.4, 121.0, 118.3, 116.6, 114.8, 55.6. HRMS (ESI) calcd for C23H20N3O2 [M+H]+: 370.1556, found 370.1559. (E)-3-((2-Chlorophenyl)amino)-2-styrylquinazolin-4(3H)-one (1s): white solid (1.49 g, 80%). IR (KBr) v (cm-1): 3318, 3060, 1689, 1633, 1607, 1548, 1471, 1449, 1334, 823, 758, 698. 1H NMR (500 MHz, DMSO-d6) δ 8.82 (s, 1H), 8.11-8.05 (m, 2H), 7.90 (t, J = 8.0 Hz, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.64 (d, J = 7.0 Hz, 2H), 7.54 19



Page 20 of 42

(t, J = 7.5 Hz, 1H), 7.46-7.39 (m, 5H), 7.10 (t, J = 8.0 Hz, 1H), 6.90 (t, J = 8.0 Hz, 1H), 6.49 (d, J = 8.0 Hz, 1H);

13C{1H}

NMR (125 MHz, CDCl3) δ 160.9, 153.6,

147.5, 142.8, 142.1, 135.6, 135.1, 130.1, 130.0, 129.0, 128.3, 128.1, 127.9, 127.2, 126.7, 123.3, 121.3, 121.2, 117.7, 114.0. HRMS (ESI) calcd for C22H17Cl1N3O1 [M+H]+: 374.1060, found 374.1062. (E)-3-((3-Chlorophenyl)amino)-2-styrylquinazolin-4(3H)-one (1t): white solid (1.56 g, 84%). IR (KBr) v (cm-1): 3242, 3079, 1667, 1632, 1607, 1548, 1469, 1448, 1342, 856, 782, 696. 1H NMR (500 MHz, DMSO-d6) δ 9.44 (s, 1H), 8.12-8.05 (m, 2H), 7.90 (t, J = 8.0 Hz, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.66 (d, J = 7.0 Hz, 2H), 7.54 (t, J = 7.5 Hz, 1H), 7.45-7.39 (m, 4H), 7.22 (t, J = 8.0 Hz, 1H), 6.89 (d, J = 8.5 Hz, 1H), 6.80 (s, 1H), 6.65 (d, J = 8.0 Hz, 1H);

13C{1H}


161.3, 153.2, 147.9, 147.5, 142.1, 135.6, 135.1, 130.8, 130.1, 129.0, 128.3, 127.9, 127.1, 126.7, 123.2, 121.0, 120.3, 117.7, 114.9, 112.8. HRMS (ESI) calcd for C22H17Cl1N3O1 [M+H]+: 374.1060, found 374.1062. (E)-3-((4-Chlorophenyl)amino)-2-styrylquinazolin-4(3H)-one (1u): white solid (1.62 g, 87%). 1H NMR (500 MHz, DMSO-d6) δ 9.37 (s, 1H), 8.12-8.04 (m, 2H), 7.89 (d, J = 7.0 Hz, 1H), 7.80 (d, J = 8.0 Hz, 1H), 7.64 (d, J = 6.5 Hz, 2H), 7.54 (d, J = 7.5 Hz, 1H), 7.45-7.39 (m, 4H), 7.24 (d, J = 9.0 Hz, 2H), 6.74 (d, J = 9.0 Hz, 2H); 13C{1H}

NMR (125 MHz, CDCl3) δ 161.3, 153.2, 147.5, 145.2, 142.0, 135.6, 135.1,

130.1, 129.7, 129.0, 128.3, 128.2, 127.9, 127.1, 126.7, 121.0, 117.8, 116.1. HRMS (ESI) calcd for C22H17Cl1N3O1 [M+H]+: 374.1060, found 374.1062. (E)-3-((4-Fluorophenyl)amino)-2-styrylquinazolin-4(3H)-one (1v): white solid 20


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(1.53 g, 86%). IR (KBr) v (cm-1): 3244, 3022, 1668, 1633, 1608, 1548, 1469, 1448, 1341, 829, 755, 695. 1H NMR (500 MHz, DMSO-d6) δ 9.21 (s, 1H), 8.11-8.05 (m, 2H), 7.89 (t, J = 7.5 Hz, 1H), 7.80 (d, J = 8.0 Hz, 1H), 7.64 (d, J = 7.0 Hz, 2H), 7.54-7.39 (m, 5H), 7.04 (t, J = 9.0 Hz, 2H), 6.76-6.73 (m, 2H);

13C{1H}

NMR (125

MHz, CDCl3) δ 161.4, 153.2, 147.5, 142.6, 141.9, 135.6, 135.0, 130.0, 129.0, 128.2, 127.9, 127.1, 126.7, 121.0, 118.0, 116.5, 116.3 (d, J = 22.9 Hz).

HRMS (ESI) calcd

for C22H17F1N3O1 [M+H]+: 358.1356, found 358.1360. (E)-2-Styryl-3-((4-(trifluoromethyl)phenyl)amino)quinazolin-4(3H)-one (1w): white solid (1.70 g, 84%). IR (KBr) v (cm-1): 3259, 3087, 1678, 1633, 1618, 1545, 1466, 1448, 1332, 831, 774, 695. 1H NMR (500 MHz, DMSO-d6) δ 9.76 (s, 1H), 8.13-8.06 (m, 2H), 7.91 (t, J = 8.5 Hz, 1H), 7.82 (d, J = 8.5 Hz, 1H), 7.65 (d, J = 7.0 Hz, 2H), 7.55 (d, J = 8.0 Hz, 3H), 7.42 (d, J = 16.5 Hz, 4H), 6.88 (d, J = 8.0 Hz, 2H); 13C{1H} NMR (125 MHz, CDCl3) δ 161.4, 153.2, 147.5, 142.6, 141.9, 135.6, 135.0, 130.0, 129.0, 128.2, 127.9, 127.1 (d, J = 4.4 Hz), 126.7, 121.0, 118.0, 116.5, 116.4, 116.2. HRMS (ESI) calcd for C23H17F3N3O1 [M+H]+: 408.1324, found 408.1330. (E)-2-(4-Methoxystyryl)-3-(phenylamino)quinazolin-4(3H)-one (1x): Pale-yellow solid (1.47 g, 80%). IR (KBr) v (cm-1): 3253, 3022, 1685, 1633, 1603, 1543, 1470, 1445, 1338, 827, 773, 690. 1H NMR (500 MHz, CDCl3) δ 8.21 (d, J = 7.5 Hz, 2H), 7.80 (m, 2H), 7.55 (d, J = 8.5 Hz, 2H), 7.44–7.41 (m, 2H), 7.26-7.22 (m, 3H), 7.00 (t, J = 7.5 Hz, 1H), 6.88 (d, J = 8.5 Hz, 2H), 6.82 (d, J = 8.0 Hz, 2H), 3.83 (s, 3H); 13C{1H}

NMR (125 MHz, CDCl3) δ 161.3, 154.0, 146.4, 134.9, 129.9, 129.5, 128.3,

127.0, 126.3, 122.9, 120.6, 114.7, 114.3, 55.4. HRMS (ESI) calcd for C23H20N3O2 21



Page 22 of 42

[M+H]+: 370.1550, found 370.1555. (E)-2-(2,5-Difluorostyryl)-3-(phenylamino)quinazolin-4(3H)-one (1y): Pale-yellow solid (1.50 g, 80%). IR (KBr) v (cm-1): 3254, 3060, 1681, 1635, 1604, 1549, 1470, 1446, 1338, 852, 780, 691. 1H NMR (500 MHz, CDCl3) δ 8.25-8.22 (m, 2H), 7.82-7.81 (m, 2H), 7.61 (d, J = 16.0 Hz, 1H), 7.49-7.46 (m, 1H), 7.27-7.23 (m, 4H), 7.06-7.00 (m, 3H), 6.81 (d, J = 7.5 Hz, 2H);

13C{1H}


161.1, 152.7, 147.2, 146.3, 134.8, 132.6, 129.5, 127.9, 127.0, 126.8, 123.0, 121.6 (d, J = 6.1 Hz), 121.2, 117.5 (dd, J1 = 9.0 Hz, J2 = 24.6 Hz), 117.2 (dd, J1 = 8.8 Hz, J2 = 25.1 Hz), 114.6, 114.4 (dd, J1 = 2.9 Hz, J2 = 24.3 Hz). HRMS (ESI) calcd for C22H16F2N3O1 [M+H]+: 376.1256, found 376.1250. (E)-2-(2,4-Dichlorostyryl)-3-(phenylamino)quinazolin-4(3H)-one (1z): Pale-yellow solid (85%). 1H NMR (500 MHz, CDCl3) δ 8.47 (d, J = 16.0 Hz, 1H), 8.23 (d, J = 8.0 Hz, 1H), 7.83 (m, 2H), 7.57-7.44 (m, 4H), 7.28-7.26 (m, 2H), 7.21 (m, 2H), 7.01 (t, J = 7.5 Hz, 1H), 6.81 (d, J = 8.0 Hz, 2H); 13C{1H} NMR (125 MHz, CDCl3) δ 161.1, 152.6, 147.3, 146.3, 136.1, 135.7, 135.4, 134.8, 132.4, 129.9, 129.6, 128.4, 128.0, 127.5, 126.9, 126.8, 123.0, 121.2, 114.6. HRMS (ESI) calcd for C22H16Cl2N3O1 [M+H]+: 408.0665, found 408.0669. (E)-3-(Isopropylamino)-2-styrylquinazolin-4(3H)-one (1za): Pale-yellow solid (1.34 g, 88%). IR (KBr) v (cm-1): 3261, 2967, 1678, 1632, 1607, 1546, 1467, 1448, 1336, 873, 771, 689. 1H NMR (500 MHz, CDCl3) δ 8.26 (d, J = 8.0 Hz, 1H), 8.06 (d, J = 16.0 Hz, 1H), 7.79 (m, 3H), 7.66 (d, J = 7.5 Hz, 2H), 7.46-7.37 (m, 4H), 5.60 (d, J = 4.0 Hz, 1H), 3.42 (m, 1H), 1.15 (m, 6H);

13C{1H}

NMR (125 MHz, CDCl3) δ 22


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161.8, 153.1, 147.3, 140.0, 135.9, 134.4, 129.6, 128.9, 127.9, 127.4, 126.7, 126.1, 120.6, 119.4, 51.8, 20.8. HRMS (ESI) calcd for C19H20N3O1 [M+H]+: 306.1601, found 306.1601.1,2-Diphenylpyrazolo[5,1-b]quinazolin-9(1H)-one (2a): Yellow solid (53.3 mg, 79%), mp 256-257 oC (lit.7a 257-258 oC). 1H NMR (500 MHz, CDCl3) δ 8.23 (d, J = 8.0 Hz, 1H), 7.74 (d, J = 4.0 Hz, 2H), 7.57-7.55 (m, 2H), 7.40-7.30 (m, 9H), 6.66 (s, 1H);

13C{1H}

NMR (125 MHz, CDCl3) δ 158.7, 156.5, 152.0, 149.5,

140.1, 133.9, 130.7, 129.6, 129.0, 128.9, 128.8, 128.0, 126.6, 126.2, 124.1, 118.0, 101.9. HRMS (ESI) calcd for C22H16N3O1 [M+H]+: 338.1288, found 338.1284. 8-Methyl-1,2-diphenylpyrazolo[5,1-b]quinazolin-9(1H)-one (2b): Yellow solid (59.7 mg, 85%), mp 257-258 oC. IR (KBr) v (cm-1): 3055, 2960, 1675, 1614, 1590, 1557, 1491, 1472, 1449, 1360, 799, 763, 689. 1H NMR (500 MHz, DMSO-d6) δ 7.70-7.68 (m, 2H), 7.61 (t, J = 8.0 Hz, 1H), 7.51-7.41 (m, 6H), 7.34-7.29 (m, 3H), 7.11 (d, J = 7.0 Hz, 1H), 7.01 (s, 1H), 2.67 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 159.5, 157.3, 152.3, 151.5, 141.2, 140.7, 133.2, 130.7, 129.4, 129.2, 129.1, 128.9, 128.4, 127.7, 126.9, 124.8, 116.9, 102.2, 23.5. HRMS (ESI) calcd for C23H18N3O1 [M+H]+: 352.1445, found 352.1441 7-Methyl-1,2-diphenylpyrazolo[5,1-b]quinazolin-9(1H)-one (2c): Yellow solid, (58.3 mg, 83%), mp 238-239 oC (lit.7a 238-239 oC). 1H NMR (500 MHz, DMSO-d6) δ 7.83 (s, 1H), 7.72-7.70 (m, 2H), 7.64-7.59 (m, 2H), 7.46-7.40 (m, 5H), 7.33-7.29 (m, 3H), 7.05 (s, 1H), 2.41 (s, 3H);

13C{1H}

NMR (125 MHz, CDCl3) δ 158.7, 156.6,

151.7, 147.8, 140.5, 135.8, 134.3, 130.7, 129.6, 129.1, 129.0, 128.9, 128.3, 128.1, 126.3, 125.8, 118.0, 102.2, 21.4. HRMS (ESI) calcd for C23H18N3O1 [M+H]+: 23



Page 24 of 42

352.1445, found 352.1440. 6-Methyl-1,2-diphenylpyrazolo[5,1-b]quinazolin-9(1H)-one (2d): Yellow solid (56.2 mg, 80%), mp 257-258 oC. IR (KBr) v (cm-1): 3064, 2956, 1681, 1618, 1588, 1544, 1483, 1447, 1360, 777, 758, 691. 1H NMR (500 MHz, DMSO-d6) δ 7.93 (d, J = 8.5 Hz, 1H), 7.71-7.69 (m, 2H), 7.48-7.41 (m, 6H), 7.33-7.30 (m, 3H), 7.21 (d, J = 8.0 Hz, 1H), 7.06 (s, 1H), 2.47 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 158.8, 156.6, 152.3, 150.0, 144.9, 140.4, 130.7, 129.6, 129.1, 129.0, 128.9, 128.3, 128.2, 126.4, 126.2, 126.0, 115.8, 102.2, 22.2. HRMS (ESI) calcd for C23H18N3O1 [M+H]+: 352.1445, found 352.1442. 5,6-Dimethyl-1,2-diphenylpyrazolo[5,1-b]quinazolin-9(1H)-one (2e): Yellow solid (59.9 mg, 82%), mp 195-196 oC. 1H NMR (500 MHz, CDCl3) δ 8.01 (d, J = 8.0 Hz, 1H), 7.56-7.55 (m, 2H), 7.38-7.26 (m, 8H), 7.16 (d, J = 8.5 Hz, 1H), 6.72 (s, 1H), 2.64 (s, 3H), 2.45 (s, 3H);

13C{1H}

NMR (125 MHz, CDCl3) δ 158.4, 156.8, 151.1,

148.1, 142.4, 140.4, 132.1, 130.5, 129.4, 128.9, 128.8, 128.7, 128.3, 128.0, 126.6, 123.3, 116.1, 102.6, 21.0, 13.5. HRMS (ESI) calcd for C24H20N3O1 [M+H]+: 366.1601, found 366.1603 7-Methoxy-1,2-diphenylpyrazolo[5,1-b]quinazolin-9(1H)-one (2f): Yellow solid (63.9 mg, 87%), mp 199-200 oC. IR (KBr) v (cm-1): 3051, 2992, 1671, 1622, 1590, 1569, 1484, 1453, 1354, 760, 703, 626. 1H NMR (500 MHz, DMSO-d6) δ 7.72-7.71 (m, 2H), 7.65 (d, J = 8.5 Hz, 1H), 7.47-7.41 (m, 7H), 7.33-7.29 (m, 3H), 7.07 (s, 1H), 3.82 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 158.2, 156.7, 156.4, 150.6, 144.7, 140.5, 130.7, 129.7, 129.1, 129.0, 128.9 128.3, 128.2, 128.1, 125.3, 118.7, 105.1, 24


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102.2, 55.8. HRMS (ESI) calcd for C23H18N3O2 [M+H]+: 368.1394, found 368.1394 7-Fluoro-1,2-diphenylpyrazolo[5,1-b]quinazolin-9(1H)-one (2g): Yellow solid (49.7 mg, 70%), mp 240-242 oC. IR (KBr) v (cm-1): 3060, 1680, 1624, 1571, 1559, 1478, 1456, 1345, 774, 761, 693. 1H NMR (500 MHz, DMSO-d6) δ 7.99 (d, J = 2.5 Hz, 1H), 7.82-7.80 (m, 1H), 7.72-7.69 (m, 3H), 7.49-7.48 (m, 2H), 7.42 (d, J = 7.0 Hz, 3H), 7.34-7.32 (m, 3H), 7.11 (s, 1H); 13C{1H} NMR (125 MHz, CDCl3) δ 160.1, 158.6, 158.2, 155.7, 155.6, 151.5, 146.1, 139.9, 130.8, 129.7, 129.1, 129.0, 128.9, 128.8, 128.4 (d, J = 8.1 Hz), 128.1, 127.9, 126.4, 123.0 (d, J = 24.7 Hz), 118.7 (d, J = 8.5 Hz), 110.8 (d, J = 23.7 Hz), 101.6. HRMS (ESI) calcd for C22H15F1N3O1 [M+H]+: 356.1194, found 356.1192 6-Fluoro-1,2-diphenylpyrazolo[5,1-b]quinazolin-9(1H)-one (2h): Yellow solid (46.2 mg, 65%), mp 264-265 oC. IR (KBr) v (cm-1): 3041, 1683, 1625, 1587, 1558, 1474, 1446, 1366, 772, 759, 690. 1H NMR (500 MHz, DMSO-d6) δ 8.12-8.09 (m, 1H), 7.71-7.69 (m, 2H), 7.49-7.47 (m, 2H), 7.43-7.41 (m, 4H), 7.34-7.32 (m, 3H), 7.26-7.22 (m, 1H), 7.08 (s, 1H);

13C{1H}

NMR (125 MHz, CDCl3) δ 167.5, 165.5,

159.0, 155.8, 152.7, 139.7, 130.9, 129.8, 129.3 (d, J = 11.1 Hz), 129.1, 129.0, 128.9, 128.8, 128.1, 127.8, 114.6, 113.3 (d, J = 24.3 Hz), 110.7 (d, J = 22.0 Hz), 101.33. HRMS (ESI) calcd for C22H15F1N3O1 [M+H]+: 356.1194, found 356.1195 8-Chloro-1,2-diphenylpyrazolo[5,1-b]quinazolin-9(1H)-one (2i): Yellow solid (52.7 mg, 71%), mp 200-202 oC. IR (KBr) v (cm-1): 3055, 1687, 1613, 1588, 1534, 1490, 1449, 1363, 801, 765, 691. 1H NMR (500 MHz, DMSO-d6) δ 8.04 (d, J = 8.5 Hz, 1H), 7.72-7.68 (m, 3H), 7.49-7.47 (m, 2H), 7.44-7.37 (m, 4H), 7.35-7.32 (m, 3H), 25



Page 26 of 42

7.10 (s, 1H); 13C{1H} NMR (125 MHz, CDCl3) δ 159.1, 156.1, 152.9, 150.7, 140.2, 139.9, 131.0, 129.9, 129.2, 129.1, 129.0, 128.3, 128.1, 128.0, 125.8, 124.8, 116.5, 101.8. HRMS (ESI) calcd for C22H15Cl1N3O1 [M+H]+: 372.0898, found 372.0894 7-Chloro-1,2-diphenylpyrazolo[5,1-b]quinazolin-9(1H)-one (2j): Yellow solid (52.0 mg, 70%), mp 235-236 oC (lit.7a 237-238 oC). 1H NMR (500 MHz, DMSO-d6) δ 7.99-7.98 (m, 1H), 7.82-7.79 (m, 1H), 7.72-7.69 (m, 3H), 7.49-7.42 (m, 5H), 7.34-7.32 (m, 3H), 7.11 (s, 1H);

13C{1H}

NMR (125 MHz, CDCl3) δ 159.0, 155.6,

152.3, 148.3, 139.9, 134.5, 130.9, 129.9, 129.6, 129.2, 129.1, 129.0, 128.2, 128.1, 128.0, 125.8, 118.9, 101.9. HRMS (ESI) calcd for C22H15Cl1N3O1 [M+H]+: 372.0898, found 372.0898 6-Chloro-1,2-diphenylpyrazolo[5,1-b]quinazolin-9(1H)-one (2k): Yellow solid (51.2 mg, 69%), mp 246-247 oC (lit.7a 246-247 oC). 1H NMR (500 MHz, DMSO-d6) δ 8.04 (d, J = 8.5 Hz, 1H), 7.72-7.69 (m, 3H), 7.49-7.48 (m, 2H), 7.43-7.37 (m, 4H), 7.34-7.33 (m, 3H), 7.10 (s, 1H);

13C{1H}

NMR (125 MHz, CDCl3) δ 159.1, 156.1,

152.9, 150.7, 140.3, 139.9, 131.0, 129.9, 129.2, 129.1, 129.0, 128.3, 128.1, 128.0, 125.7, 124.8, 116.5, 101.8. HRMS (ESI) calcd for C22H15Cl1N3O1 [M+H]+: 372.0898, found 372.0897 7-Bromo-1,2-diphenylpyrazolo[5,1-b]quinazolin-9(1H)-one

(2l):

Yellow

solid

(64.8 mg, 78%), (lit.7a 259-260 oC), mp 260-261 oC. 1H NMR (500 MHz, DMSO-d6) δ 8.13-8.12 (m, 1H), 7.92-7.90 (m, 1H), 7.70-7.69 (m, 2H), 7.63 (d, J = 9.0 Hz, 1H), 7.49-7.42 (m, 5H), 7.34-7.32 (m, 3H), 7.10(s, 1H); 13C{1H} NMR (125 MHz, CDCl3) δ 159.1, 155.5, 152.4, 148.6, 139.9, 137.2, 131.0, 129.9, 129.2, 129.1, 129.0, 128.9, 26


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128.3, 128.2, 128.0, 119.4, 117.1, 101.9. HRMS (ESI) calcd for C22H15Br1N3O1 [M+H]+: 416.0393, found 416.0397 7-Iodo-1,2-diphenylpyrazolo[5,1-b]quinazolin-9(1H)-one (2m): Yellow solid (65.8 mg, 71%), mp 250-252 oC. IR (KBr) v (cm-1): 3061, 1673, 1603, 1581, 1533, 1489, 1460, 1333, 828, 764, 694. 1H NMR (500 MHz, DMSO-d6) δ 8.31-8.30 (m, 1H), 8.05-8.02 (m, 1H), 7.70-7.69 (m, 2H), 7.49-7.46 (m, 3H), 7.42 (d, J = 7.0 Hz, 3H), 7.33-7.32 (m, 3H), 7.09 (s, 1H);

13C{1H}

NMR (125 MHz, CDCl3) δ 159.2, 155.2,

152.5, 149.1, 142.6, 139.9, 135.5, 131.0, 129.9, 129.2, 129.1, 129.0, 128.4, 128.2, 128.0, 119.8, 101.9, 87.3. HRMS (ESI) calcd for C22H15I1N3O1 [M+H]+: 464.0255, found 464.0258 1,2-Diphenyl-7-(trifluoromethyl)pyrazolo[5,1-b]quinazolin-9(1H)-one

(2n):

Yellow solid (48.6 mg, 60%), mp 248-250 oC. IR (KBr) v (cm-1): 2959, 1684, 1590, 1548, 1533, 1488, 1453, 1316, 838, 767, 668. 1H NMR (500 MHz, CDCl3) δ 8.52 (s, 1H), 7.90-7.88 (m, 1H), 7.80 (d, J = 9.0 Hz, 1H), 7.56-7.54 (m, 2H), 7.40-7.33 (m, 8H), 6.69 (s, 1H);

13C{1H}

NMR (125 MHz, CDCl3) δ 159.1, 155.8, 153.1, 151.5,

139.3, 131.0, 129.9, 129.9, 129.1, 129.0, 128.9, 128.2, 127.5, 127.1, 126.4, 125.8, 125.5, 125.1, 124.8 (d, J = 4.3 Hz), 122.9, 117.1, 101.4.

HRMS (ESI) calcd for

C23H14F3N3O1Na [M+Na]+: 428.0987, found 428.0972 2-Phenyl-1-(o-tolyl)pyrazolo[5,1-b]quinazolin-9(1H)-one (2o): Yellow solid (47.1 mg, 67%), mp 220-221 oC. IR (KBr) v (cm-1): 3081, 1684, 1601, 1548, 1560, 1479, 1456, 1345, 815, 767, 698. 1H NMR (500 MHz, DMSO-d6) δ 8.05 (d, J = 7.0 Hz, 1H), 7.80-7.77 (m, 1H), 7.67 (d, J = 8.0 Hz, 1H), 7.59-7.58 (m, 2H), 7.43-7.41 (m, 27



Page 28 of 42

3H), 7.36 (t, J = 8.0 Hz, 1H), 7.26-7.24 (m, 3H), 7.15-7.12 (m, 1H), 7.04 (s, 1H), 2.29 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 157.1, 156.4, 151.5, 149.9, 138.4, 137.9, 134.0, 131.1, 130.7, 130.1, 128.9, 128.8, 128.6, 128.2, 126.7, 126.6, 126.3, 123.8, 117.7, 100.5, 18.2. HRMS (ESI) calcd for C23H18N3O1 [M+H]+: 352.1445, found 352.1447 2-Phenyl-1-(m-tolyl)pyrazolo[5,1-b]quinazolin-9(1H)-one (2p): Yellow solid (57.6 mg, 82%), mp 241-242 oC. IR (KBr) v (cm-1): 3076, 1682, 1592, 1550, 1488, 1467, 1447, 1362, 808, 770, 688. 1H NMR (500 MHz, DMSO-d6) δ 8.05 (d, J = 8.0 Hz, 1H), 7.81-7.68 (m, 4H), 7.43-7.32 (m, 5H), 7.23-7.20 (m, 2H), 7.11 (d, J = 7.5 Hz, 1H), 7.07 (s, 1H), 2.21 (s, 3H);

13C{1H}

NMR (125 MHz, CDCl3) δ 159.0, 156.6,

152.2, 149.8, 140.2, 139.0, 134.0, 130.8, 130.5, 129.1, 128.9, 128.7, 128.2, 128.1, 126.7, 126.4, 125.3, 124.2, 118.1, 102.0, 21.4. HRMS (ESI) calcd for C23H18N3O1 [M+H]+: 352.1445, found 352.1439 2-Phenyl-1-(p-tolyl)pyrazolo[5,1-b]quinazolin-9(1H)-one (2q): Yellow solid (56.2 mg, 80%), mp 273-274 oC (lit.7a 273-274 oC). 1H NMR (500 MHz, DMSO-d6) δ 8.05 (d, J = 7.0 Hz, 1H), 7.81-7.78 (m, 1H), 7.72-7.67 (m, 3H), 7.43-7.33 (m, 6H), 7.12 (d, J = 8.0 Hz, 2H), 7.06 (s, 1H), 2.24 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 158.7, 156.4, 151.8, 149.2, 139.8, 137.3, 134.0, 130.7, 129.6, 129.1, 128.8, 128.0, 127.9, 126.6, 126.0, 124.1, 117.8, 101.4, 21.3. HRMS (ESI) calcd for C23H18N3O1 [M+H]+: 352.1445, found 352.1444 1-(4-Methoxyphenyl)-2-phenylpyrazolo[5,1-b]quinazolin-9(1H)-one (2r): Yellow solid (62.4 mg, 85%), mp 244-245 oC. IR (KBr) v (cm-1): 3080, 1676, 1597, 1553, 28


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1507, 1463, 1449, 1328, 844, 760, 686. 1H NMR (500 MHz, CDCl3) δ 8.23 (d, J = 8.0 Hz, 1H), 7.74-7.73 (m, 2H), 7.57-7.55 (m, 2H), 7.38-7.31 (m, 6H), 6.80 (d, J = 9.0 Hz, 2H), 6.67 (s, 1H), 3.75 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 160.1, 158.6, 156.5, 151.8, 149.2, 134.0, 132.2, 130.7, 129.6, 129.0, 128.8, 128.0, 126.6, 125.9, 124.1, 117.9, 114.0, 101.2, 55.4. HRMS (ESI) calcd for C23H18N3O2 [M+H]+: 368.1394, found 368.1405 1-(2-Chlorophenyl)-2-phenylpyrazolo[5,1-b]quinazolin-9(1H)-one

(2s):

Yellow

solid (40.8 mg, 55%), mp 215-216 oC. IR (KBr) v (cm-1): 3060, 1680, 1587, 1548, 1489, 1467, 1448, 1325, 811, 766, 689. 1H NMR (500 MHz, DMSO-d6) δ 8.06 (d, J = 8.0 Hz, 1H), 7.84-7.78 (m, 2H), 7.69-7.66 (m, 3H), 7.46-7.36 (m, 7H), 7.06 (s, 1H); 13C{1H}

NMR (125 MHz, CDCl3) δ 157.0, 156.4, 151.4, 149.8, 136.4, 134.8, 134.1,

131.7, 131.3, 130.9, 130.4, 129.0, 128.9, 127.8, 127.3, 126.6, 126.5, 124.0, 117.7, 101.3. HRMS (ESI) calcd for C22H15Cl1N3O1 [M+H]+: 372.0898, found 372.0889 1-(3-Chlorophenyl)-2-phenylpyrazolo[5,1-b]quinazolin-9(1H)-one

(2t):

Yellow

solid (52.0 mg, 70%), mp 208-209 oC. IR (KBr) v (cm-1): 3056, 1674, 1597, 1550, 1489, 1467, 1447, 1328, 792, 762, 694. 1H NMR (500 MHz, DMSO-d6) δ 8.07 (d, J = 7.0 Hz, 1H), 7.83-7.79 (m, 1H), 7.74-7.69 (m, 4H), 7.46-7.32 (m, 7H), 7.10 (s, 1H); 13C{1H}

NMR (125 MHz, CDCl3) δ 158.9, 156.6, 152.1, 149.7, 141.5, 134.6, 134.2,

131.1, 130.1, 129.9, 129.1, 129.0, 128.0, 127.8, 126.6, 124.6, 118.2, 102.9. HRMS (ESI) calcd for C22H15Cl1N3O1 [M+H]+: 372.0898, found 372.0894 1-(4-Chlorophenyl)-2-phenylpyrazolo[5,1-b]quinazolin-9(1H)-one (2u): Yellow solid (49.0 mg, 66%), mp 220-221 oC (lit.7a 220-221 oC). 1H NMR (500 MHz, 29



Page 30 of 42

DMSO-d6) δ 8.06 (d, J = 8.0 Hz, 1H), 7.81 (t, J = 7.5 Hz, 1H), 7.72-7.69 (m, 3H), 7.54 (d, J = 7.5 Hz, 2H), 7.45-7.39 (m, 6H), 7.11 (s, 1H); 13C{1H} NMR (125 MHz, CDCl3) δ 158.8, 156.7, 152.1, 149.8, 138.9, 135.6, 134.2, 131.0, 129.5, 129.4, 129.1, 129.0, 127.9, 126.6, 126.5, 124.5, 118.2, 102.6. HRMS (ESI) calcd for C22H15Cl1N3O1 [M+H]+: 372.0898, found 372.0897 1-(4-Fluorophenyl)-2-phenylpyrazolo[5,1-b]quinazolin-9(1H)-one

(2v):

Yellow

solid (46.2 mg, 65%), mp 197-200 oC. IR (KBr) v (cm-1): 3034, 1682, 1589, 1551, 1501, 1467, 1449, 1361, 844, 773, 690. 1H NMR (500 MHz, DMSO-d6) δ 8.06 (d, J = 7.5 Hz, 1H), 7.82-7.78 (m, 1H), 7.72-7.68 (m, 3H), 7.58-7.55 (m, 2H), 7.44-7.37 (m, 4H), 7.16 (t, J = 8.5 Hz, 2H), 7.09 (s, 1H); 13C{1H} NMR (125 MHz, CDCl3) δ 158.9, 156.8, 152.0, 149.8, 136.1, 134.2, 131.0, 130.2 (d, J = 9.1 Hz), 129.0 (d, J = 2.2 Hz), 128.0, 126.5 (d, J = 7.3 Hz), 124.4, 118.2, 116.1 (d, J = 23.2 Hz), 102.3. HRMS (ESI) calcd for C22H15F1N3O1 [M+H]+: 356.1194, found 356.1199 2-Phenyl-1-(4-(trifluoromethyl)phenyl)pyrazolo[5,1-b]quinazolin-9(1H)-one (2w): Yellow solid (50.2 mg, 62%), mp 211-212 oC. IR (KBr) v (cm-1): 3080, 1686, 1592, 1553, 1490, 1462, 1448, 1330, 852, 759, 689. 1H NMR (500 MHz, DMSO-d6) δ 8.06 (d, J = 7.0 Hz, 1H), 7.84-7.80 (m, 1H), 7.75-7.70 (m, 7H), 7.46-7.39 (m, 4H), 7.14 (s, 1H);

13C{1H}

NMR (125 MHz, CDCl3) δ 158.9, 156.6, 152.0, 149.7, 143.6, 134.3,

131.2, 129.2, 129.1, 128.4, 127.8, 126.7, 126.6, 126.3 (d, J = 3.6 Hz), 124.7, 118.1, 103.2. HRMS (ESI) calcd for C23H15F3N3O1 [M+H]+: 406.1162, found 406.1165 2-(4-Methoxyphenyl)-1-phenylpyrazolo[5,1-b]quinazolin-9(1H)-one (2x): Yellow solid (62.4 mg, 85%). mp 220-222oC. IR (KBr) v (cm-1): 3076, 1684, 1597, 1555, 30


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1502, 1467, 1447, 1362, 833, 756, 690. 1H NMR (500 MHz, CDCl3) δ 8.22 (d, J = 8.0 Hz, 1H), 7.73 (d, J = 4.0 Hz, 2H), 7.50 (d, J = 9.0 Hz, 2H), 7.41-7.39 (m, 2H), 7.33-7.32 (m, 4H), 6.86 (d, J = 8.5 Hz, 2H), 6.61 (s, 1H), 3.79 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 161.5, 158.8, 156.5, 152.1, 140.4, 134.0, 130.5, 129.6, 128.9, 128.2, 126.6, 126.0, 124.0, 120.2, 117.8, 114.3, 100.6, 55.4. HRMS (ESI) calcd for C23H18N3O2 [M+H]+: 368.1394, found 368.1388. 2-(2,4-Difluorophenyl)-1-phenylpyrazolo[5,1-b]quinazolin-9(1H)-one (2y): Yellow solid (21.6 mg, 29%). mp 280-282 oC. IR (KBr) v (cm-1): 3057, 1683, 1597, 1533, 1503, 1470, 1447, 1333, 845, 777, 688. 1H NMR (500 MHz, CDCl3) δ 8.24 (d, J = 8.0 Hz, 1H), 7.78-7.75 (m, 2H), 7.38-7.34 (m, 6H), 7.17 (s, 1H), 7.10-7.07 (m, 2H), 6.82 (s, 1H); 13C{1H} NMR (125 MHz, CDCl3) δ 159.2, 157.2, 156.1, 151.4, 151.1, 139.3, 134.2, 129.9, 129.1, 127.4, 126.6, 126.1, 124.6, 119.3, 119.2 (d, J = 22.1 Hz), 119.1 (d, J = 21.9 Hz), 117.9, 117.8, 117.6 (d, J = 24.5 Hz), 117.5 (d, J = 19.9 Hz), 105.0. HRMS (ESI) calcd for C22H14F2N3O1 [M+H]+: 374.1100, found 374.1101. 1-Isopropyl-2-phenylpyrazolo[5,1-b]quinazolin-9(1H)-one (2za): Yellow oil (47.9 mg, 79%). IR (KBr) v (cm-1): 3003, 1698, 1613, 1607, 1550, 1467, 1450, 1346, 853, 778, 699. 1H NMR (500 MHz, CDCl3) δ 8.37 (d, J = 8.0 Hz, 1H), 7.75-7.68 (m, 2H), 7.64-7.62 (m, 2H), 7.54-7.52 (m, 3H), 7.38 (t, J = 7.5 Hz, 1H), 6.38 (s, 1H), 4.80-4.77 (m, 1H), 1.29 (d, J = 7.0 Hz, 6H); 13C{1H} NMR (125 MHz, CDCl3) δ 159.8, 157.8, 152.9, 149.4, 133.9, 130.9, 130.3, 129.0, 126.7, 126.1, 123.9, 117.5, 102.9, 56.6, 20.2. HRMS (ESI) calcd for C19H18N3O1 [M+H]+: 304.1445, found 304.1448. 1,2-Diphenylpyrazolo[5,1-b]quinazolin-9(1H)-one-4-ium iodide (3a): Yellow solid 31



Page 32 of 42

(91.0mg, 95%), mp 273-275 oC. 1H NMR (500 MHz, DMSO-d6) δ 8.23 (d, J = 8.0 Hz, 1H), 8.15 (t, J = 8.0 Hz, 1H), 8.02 (d, J = 8.5 Hz, 1H), 7.88 (s, 1H), 7.71-7.62 (m, 5H), 7.58-7.49 (m, 6H), 4.15 (s, 3H); 13C{1H} NMR (125 MHz, DMSO-d6) δ 157.4, 153.3, 148.9, 139.5, 136.9, 136.3, 132.1, 130.9, 129.7, 129.1, 129.0, 127.8, 125.8, 125.2, 116.3, 115.4, 95.3, 36.1. HRMS (ESI) calcd for C23H18N3O [M-I]+: 352.1444, found 352.1455 (E)-3-(Methyl(phenyl)amino)-2-styrylquinazolin-4(3H)-one (4a): Pale-yellow solid (158.9mg, 90%). IR (KBr) v (cm-1): 2924, 2891, 1687, 1629, 1597, 1550, 1471, 1448, 1357, 825, 756, 699. 1H NMR (500 MHz, CDCl3) δ 8.19 (m, 2H), 7.80 (m, 2H), 7.58 (m, 2H), 7.43 (t, J = 7.0 Hz, 1H), 7.35 (m, 4H), 7.28 (t, J = 8.0 Hz, 2H), 6.92 (t, J = 7.0 Hz, 1H), 6.74 (d, J = 8.0 Hz, 2H), 3.49 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 160.4, 154.6, 147.9, 147.2, 142.1, 135.5, 134.8, 129.9, 129.5, 128.8, 128.1, 127.5, 127.1, 126.5, 122.2, 120.7, 117.7, 112.7, 39.4. HRMS (ESI) calcd for C23H20N3O1 [M+H]+: 354.1606, found 354.1609 (Z)-3-(methyl(phenyl)amino)-2-(2-phenyl-1-(phenylselanyl)vinyl)quinazolin-4(3H)one (5a): yellow solid (50.9 mg, 50%). mp 65-66 oC. IR (KBr) v (cm-1): 2981, 2885, 1695, 1603, 1588, 1547, 1477, 1447, 1339, 805, 731, 689. 1H NMR (500 MHz, CDCl3) δ 8.22-8.19 (m, 2H), 7.83-7.79 (m, 2H), 7.60-7.59 (m, 2H), 7.48-7.36 (m, 8H), 7.29-7.20 (m, 4H), 6.68 (d, J = 8.0 Hz, 2H), 3.50 (s, 3H);

13C{1H}

NMR (125

MHz, CDCl3) δ 160.3, 154.3, 147.8, 147.0, 142.6, 136.1, 135.3, 135.0, 132.6, 131.5, 130.1, 129.2, 128.9, 128.2, 127.5, 127.1, 126.6, 122.0, 120.3, 117.2, 113.6, 39.5. HRMS (ESI) calcd for C29H24N3O1Se1 [M+H]+: 510.1079, found 510.1085 32


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ASSOCIATED CONTENT Supporting Information 1H

and 13C NMR spectra for all products. This material is available free of charge on

the ACS Publications website. The X-ray crystallographic analysis data and copies of NMR spectra (PDF) CIF file for compounds 2a and 3a (CIF) AUTHOR INFORMATION Corresponding Author E-mail: [email protected]; E-mail: [email protected] ORCID Jiuxi Chen: 0000-0001-6666-9813 Yinlin Shao: 0000-0003-1935-0345 Notes The authors declare no competing ﬁnancial interest. ACKNOWLEDGMENTS We thank the National Natural Science Foundation of China (No. 21572162), the Natural Science Foundation of Zhejiang Province (LQ18B020006), the Science and Technology Project of Zhejiang Province (No. 2016C31022) and the Xinmiao Talent Planning Foundation of Zhejiang Province (No. 2017R426046) for financial support. 33



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