Synthesis of 1,2-Dihydroquinazolines via Rearrangement of

Subscriber access provided by Kaohsiung Medical University

Note

Synthesis of 1,2-Dihydroquinazolines via Rearrangement of Indazolium Salts Qian Chen, Zhuqing Mao, Kunqi Gao, Fang Guo, Li Sheng, and Zhonglin Chen J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01044 • Publication Date (Web): 17 Jul 2018 Downloaded from http://pubs.acs.org on July 17, 2018

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 16 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

The Journal of Organic Chemistry

Synthesis of 1, 2-Dihy ihydroquinazolines via Rearrangement of Indazolium Salts alts Qian Chen,a,b * Zhuqing Mao, b Kunqi Gao,b Fang Guo,b Li Sheng, b* Zhonglin Chen c*

a. School of Chemical Engineering, Southwest Forestry University, Kunming, 650224, China. E-mail: [email protected]. b. School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, 150080, China. E-mail: [email protected]. c. State Key Laboratory of Urban Water Resource and Environment, School of Environment, Harbin Institute of Technology, Harbin, 150090, China. E-mail: [email protected].

Abstract: Abstract A convenient synthesis of 1,2-dihydroquinazolines via rearrangement of indazolium salts was described. A mechanistic study using isotope labelling experiment revealed that the rearrangement passes through cleavage of N-N bond/ring opening after basic deprotonation of 2-benzyl in indazolium salts to yield intermediate E, which proceeds in an intramolecular N-nucleophilic addition to form the observed product. Computational analyses imply that the pathway of the rearrangement is determined by the energy barriers of the ring-closing process and the stability of the product. The quinazoline skeleton is a common structural motif in the N-containing heterocycles compounds with an extensive spectrum of bioactivities.1 Recent research results of the quinazoline analogues shown that their potential applications in antibacterial,2 anticancer,3 antiviral,4

antiinflammatory

activities,5

antimalarial

activities,6 and

calcium

channel

antagonists.7 Dihydroquinazoline derivatives are known to act as selective inhibitors of the trypanothione reductase (TryR).8 Considerable efforts have been made towards the synthesis of these quinazoline and dihydroquinazoline derivatives because of above-mentioned application possibilities.

7b, 7c, 7d, 8, 9

For example, Movassaghi reported the synthesis of

ACS Paragon Plus Environment

The Journal of Organic Chemistry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 2 of 16

quinazoline derivatives by using benzamides and alkylnitriles in the presence of Tf2O and a base additive. 9a Buchwald described an efficient approach for preparing quinazolines through a Pd-catalyzed N-arylation of amidines followed by addition of aldehydes.9k Mancheño’s group disclosed a straightforward iron catalyzed oxidative tandem procedure for the synthesis of dihydroquinazolines from N-alkylanilines using TEMPO oxoammonium salt as an oxidant.

9d

Dihydroquinazolines skeleton can be constructed from 2-aminobenzophenone and aldehydes under microwave irradiation. 9b Although these reported methods are efficient, the mild and rapid approaches for the synthesis of dihydroquinazolines from readily available starting materials would still be desired. Carbenes containing a divalent carbon atom have been regarded as highly reactive species in organic transformations. 10 The preparation of the first isolable carbene bearing adjacent phosphorus and silicon substituents was only achieved three decades ago by Bertrand and co-workers; this study ushered a dramatic surge in the research on isolable carbene.11 NHCs have become one of the most significant developments in both organometallic chemistry and organocatalysis.12 NHCs have been widely utilized as alternatives to phosphine ligands for transition metal-catalytic reactions because of their strong σ-donating ability and high stability toward oxygen and moisture.13,14 The steric hindrance and electronic properties of NHCs can also be readily fine-tuned through the variation in the backbone of N-heterocycles and/or

N-substituents.15 NHCs with a carbene center adjacent to only one heteroatom have shown some different features from that of NHCs adjacent to two heteroatoms, such as imidazole, imidazoline and benzimidazoline. 16,17 Indazolin-3-ylidenes are the representative examples of this class of NHCs and their coordination chemistry and utility as ligands were investigated.18

We also described the use of indazolium salts as efficient carbene precursors for palladium-catalyzed Suzuki coupling of aryl bromides with arylboronic acids.19 As a rational extension, we attempted to use indazolium salts for the palladium-catalytic Heck reaction between ester acrylate with aryl bromide. Unexpectedly, we were unable to obtain the Heck reaction product and a trace of new compound was isolated. After analysis of the spectrum of the new compound, we inferred that the new compound possibly came from the rearrangement of indazolium salts. Molecular rearrangement has gained considerable attention in organic synthesis, because it represents a new pathway based on the reorganization of the bonds of easily available reactants.

20

Several

examples of organic synthesis based on N-N bond cleavage have been reported,

21 and

have also been considered to be fairly helpful in understanding the mechanisms of nitrogen fixation and searching the possibility of developing new transformations that can utilize molecular nitrogen and/or others compounds containing N-N bond.22 However, reports on the molecular rearrangement based on N-N bond cleavage have been scarce. Rearrangement of NHCs of pyrazoles and indazols were observed, which can be used as an approach for the synthesis of 4-aminoquinolines, acridines, and the relative compounds (Scheme 1a).

23

Interestingly, the present rearrangement demonstrated a


Page 3 of 16 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


different mechanism from previous reports and produced 1,2-dihydroquinazolines (Scheme 1b). Herein, we report the rearrangement of the indazolium salts bearing various

N-substituents and their mechanism by experiment and density functional theory (DFT) calculation. Scheme 1. 1 The rearrangement of indazoliums

Based on the primary discovery, indazolium bromide 1a was examined as the model compound to optimize the rearrangement condition (Table 1). The initial screening of solvents indicated that toluene, dioxane and DMSO are suitable for the study, whereas DMF and THF yielded moderate results (entries 1–5). The present rearrangement is tolerant to H2O (entry 6). Considering the convenience of being free of workup, we opted to use toluene as solvent. Lower yields were observed when the reaction temperature was lowered (entries 7–8). Investigations into the effects of bases suggested that Cs2CO3, K2CO3, Na2CO3 and K3PO4 are suitable bases for the present rearrangement reaction (entries 9–11). However, Et3N proved to be less effective (entry 12). We also attempted to determine the possibility of asymmetric version using (+)-cinchonine as base. However, racemic target compound was obtained in reasonable yield (entry 13).

Table 1. 1 Optimization of the rearrangement reaction conditions[a]

Entry

Solvent

Base

T(℃)

Yield (%)[b]

1

toluene

Cs2CO3

70

82

2

dioxane

Cs2CO3

70

76

3

THF

Cs2CO3

70

67

4

DMF

Cs2CO3

70

65

5

DMSO

Cs2CO3

70

75

6

toluene/H2O

Cs2CO3

70

60

7

toluene

Cs2CO3

50

70

8

toluene

Cs2CO3

rt

40

9

toluene

K2CO3

70

84

10

toluene

Na2CO3

70

83

11

toluene

K3PO4

70

67

12

toluene

Et3N

70

21

13

toluene

(+)-cinchonine

70

50

[a]. Reaction condition: indazolium halides (0.2 mmol), base (0.3 mmol), solvent (2 mL) at 70 ℃ for 12 hours. [b]. Isolated yield.

With the identified optimal reaction conditions (Table 1, entry 9), we first evaluated the different functionalities of N-substituted benzyl in indazolium salts. Scheme 2 shows that the different



Page 4 of 16

substituents and substitution patterns of the N-substituted benzyl of indazolium salts were all tolerated. Methyl substituted 1b–1d 1b 1d were successfully transferred into the corresponding 2b–2d 2b 2d in good to high yields (70%–95%). A bulkier substrate with mesityl group also provided the desired product 2e in good yield. Indazolium salts containing strong electron-donating substituted aryl group were good substrates for the present rearrangement, affording the desired product in high yields (2f 2f–2g 2f 2g). 2g Substrates bearing electron-withdrawing substituted aryl groups, including chloro-, fluoro- and nitro-groups were tested for the present rearrangement, and the desired rearrangement products were afforded in moderate to good yields (2h 2h–2m 2h 2m). 2m Results indicate that electronic property and steric hindrance on the N-substituted benzyl had a slight effect on the observed rearrangement. Scheme 2. Scope for the rearrangement reactiona,b.

Further investigations showed that the present rearrangement has a broad substrate scope (Scheme 2). Indazolium salts with 1-methyl and 1-ethyl groups were good substrates for the present rearrangement, forming the desired product in good to high yields (2n 2n–2p 2n 2p). 2p Furthermore, substrates, the core aryl groups of which have electron-donating and electron-withdrawing substituted groups, including methoxy, benzyloxy, and bromo groups, were examined for the present rearrangement, and the corresponding rearrangement products were obtained in moderate to high yields (2q 2q–2z 2q 2z). 2z Indazolium salt, whose 2-benzyl group replaced by a cinnamyl group, was a good substrate for the present rearrangement, producing 3a in high yield. Next, we investigated the mechanism of the present rearrangement. Initially, we supposed that the rearrangement should be followed a mechanism as shown in Scheme 3.

23

Thus,

deprotonation of 1a by base gave ylide A or carbene A’, which proceeds cleavage of N-N bond/ring opening to afford an intermediate keteneimine B. 1,3–H shift or 1,5’–H shift of the keteneimine B produces intermediate C or D, respectively.24 6π−Electrocyclization of the intermediate C gave the observed product 2a. 2a However, another possible rearrangement


Page 5 of 16 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


product 4 derived from intermediate D through 1,5’–H shift could not be detected, which ruled out the possibility of 1,5’–H shift. If it is true, the rearrangement of deuterated 1-benzyl or 2-benzyl should give two different products. Scheme 3. Proposed rearrangement mechanism I.

Thus, the rearrangement of isotope labeling 1-benzyl and 2-benzyl 1a were carried out at the same condition as that of 1a (Scheme 4). Interestingly, the rearrangement of 1a-1-benzyl 1a D2 gave the expected 2a-1-benzyl D2 containing total D, while 1a-2-benzyl D2 gave 2a 1a 2a-2-benzyl D containing 58-64% D and the desired 2a-2, 2a 2a 4-di-D was not observed. This result implies that the present rearrangement did not proceed 1, 3-H shift of the keteneimine B. Scheme 4. Isotope labelling experiment of the rearrangement.

Based on the above results, we propose the second mechanism of the rearrangements, as shown in Scheme 5. Given the intramolecular N-nucleophilic addition of intermediate E or 6π−electrocyclization of the intermediate C to obtain the desired product 2a, 2a we speculated that formation of intermediate G through deprotonation of 2-benzyl in 1a with bases and subsequent cleavage of N-N bond/ring opening yielded intermediate E or its non-polar resonance structure C (Scheme 5, top). In principle, formation of intermediate H through deprotonation of 1-benzyl in 1a with bases and similar cleavage of N-N bond/ring opening process could yield intermediate F or its non-polar resonance structure D, proceeding in a similar rout to form the product 4 (Scheme 5, bottom). However, the conceivable rearrangement product 4 was not observed. We estimated that the observed regioisomeric product resulted from the difference in the stability of transition state and/or intermediates of both E and F (video post). The observed facts can be readily explained following the new mechanism of these rearrangements. We ascribe the lower deuterated ratio of 2a-2-benzyl D 2a (58%–64%) to the exchange of proton with deuterium under alkalic conditions.25 Scheme 5. Proposed mechanism for the rearrangement II.



N Ph

N

C Ph

N H base 2-Benzyl

n

N

Ph

N

Ph

Ph

tio za cli cy t ro ec

top

El

N N+

G

Ph

N

Ph N

NPh

Ph N

F

Ph Ph

4 Ph

N

Ph

N

Ph

ct ro

Ph 1-Benzyl base

N n

N N

N

N+

cy cl iz

Ph

H

Ph

N-

bottom

Ph

2a Ph Observed

E

at io

1a

H N D

El e

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Ph

We carried out quantum chemical calculations for the reaction pathway to gain further understanding of the mechanism of the present rearrangements (see SI for computational details).26 The equilibrium geometries of indazolium are presented in Figure 1. As shown in Figure 1, the DFT-calculated Mulliken charge (Q) of N1 atom differs significantly from that of the N2 atom. The N1 possesses a negative charge of 0.389, which is 0.156 greater than the 0.233 value for N2. Meanwhile, H1 and H2 possess almost the same positive charge of around 0.248. The calculated pKa values of H1 and H2 are 0.15 and 0.14 at 70℃, respectively, which can be regarded that the acidity of H1 equals to the acidity of H2. Therefore, the charge difference of N1 and N2 has no effect on the activity of H atoms. However, because of its more negative charge, N1 can attack C2 more easily than when N2 attacks C1. The results are in line with the observed regioselectivity outcomes. Furthermore, the results are in accordance with the following energy analyses.

Figure 1. Equilibrium geometries of indazolium. Part Mulliken charges and part bond length (Å) are signed. H: white, C: yellow, N:blue.

The calculated energy profiles of the main reaction (MR) (Scheme 5, top) and side reaction (SR) pathways (Scheme 5, bottom) are depicted in Figure 2. In our calculation, the reaction mechanism involves ring-opening and ring-closing processes. In the ring-opening process, MR and SR, exhibit almost same energy barriers, which are 7.3 and 6.1 kcal mol-1, respectively. The SR intermediate F is much more stable than the MR intermediate E. However, in the ring-closing process, the energy barriers of MR and SR are 3.7 and 11.4 kcal mol-1, respectively, and the MR product 2a is more stable by 15.9 kcal mol-1 than that of SR product 4. As a result, the MR product 2a is the proposed product. The results, which are in agreement with the observed regioselectivity, suggest that the reaction route of the present rearrangement is determined by the energy barriers of the ring-closing step and the stability of the rearrangement product. We also estimated the synergic reaction pathways, i.e. the reaction with the simultaneous breaking of old bonds (N1-N2 bond) and formation of new bonds (N1-C2 bond) through a three-member ring transition state (TS)(Scheme 6). 27 In this calculation, the angle of N1-N2-C2 was fixed at a reasonable angle (from 70° to 150° by step size 5°), and other structural parameters were optimized. The energy curve formed by each minimized energy shows that the concerted reaction had to overcome a huge energy barrier of more than 40 kcal mol-1. Therefore, this reaction path is highly unlikely to occur.


Page 6 of 16

Page 7 of 16 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Figure 2. Energy profile of minimum energy path for indazolium rearrangement.

Scheme 6. Proposed synergic reaction pathway.

Conclusions In summary, we disclosed the rearrangement of indazolium salts bearing various N-substituents under mild conditions, producing 1,2-dihydroquinazolines. Research on the mechanism through isotope labelling experiment and DFT calculation imply that the present rearrangement passes through a cleavage of N-N bond/ring opening after deprotonation of 2-benzyl in 1a with base to yield intermediate E. The reaction then proceeds as an intramolecular N-nucleophilic addition to yield the observed product 2a. 2a The reaction pathway of the present rearrangement was determined by the energy barriers of the ring-closing process and the stability of the product. The rearrangement products with a broad range of substituted benzyl or alkyl were obtained in good to high yields. Further transformation potential and possible bioactive test are currently underway. ■ EXPERIMENTAL SECTION

General.1H and 13C NMR data was acquired on a Bruker AV-400 MHz spectrometer. HRMS were obtained from Agilent 6520 Q-TOF LC/MS. Commercial reagents were purchased and used without further purification. THF and toluene were distilled over benzophenone ketyl under nitrogen. DMF was distilled over CaH2 under nitrogen. Dioxane was distilled over LiAlH4 under nitrogen. Indazolium halides were prepared according to our provious procedure 19. General procedure for ringring-enlargemeng rearrangement rearrangement of indazolium salts. salts. A reaction tube was charged with indazolium salt (0.20 mmol), potassium carbonate (0.30 mmol). To the reaction tube was added toluene (2.0 mL). The mixture was stirred at 70 °C for several hours. The mixture was cooled to room temperature and directly purified through silica gel column chromatography to give the product.



Page 8 of 16

1-benzyl-2-phenyl-1,2-dihydroquinazoline （ 2a ） . Silica gel column chromatography (hexane/AcOEt =3/1) gave 2a as a white solid (50 mg, 84 %), mp 140–142 °C; 1H NMR (400 MHz, CDCl3): δ 8.11 (s, 1H), 7.39–7.23 (m, 10H), 7.17 (dd, J = 7.4 and 8.4 Hz, 1H), 7.09 (d, J = 7.6 Hz, 1H), 6.63 (dd, J = 7.6 and 8.0 Hz, 1H), 6.50 (d, J = 8.0 Hz, 1H), 6.27 (s, 1H), 4.55 (d, J = 8.8 Hz, 1H), 4.17 (d, J = 8.0 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 157.5, 145.3, 141.3, 136.8, 133.9, 128.74, 128.67, 128.4, 127.3, 126.9, 126.4, 116.9, 116.7, 110.8, 78.9, 50.7. HRMS-ESI(m/z): Calcd for C21H19N2 [M+H]+ 299.1543, Found: 299.1523.

2a -1-benzyl- D2 . Silica gel column chromatography (hexane/AcOEt =3/1) gave 2a -1-benzyl- D2 as a white solid (15 mg, 88 %), mp 127–129 °C; 1H NMR (400 MHz, CDCl3): δ 8.11 (s, 1H), 7.39–7.23 (m, 10H), 7.17 (dd, J = 7.4 and 8.4 Hz, 1H), 7.09 (d, J = 7.6 Hz, 1H), 6.63 (dd, J = 7.6 and 8.0 Hz, 1H), 6.50 (d, J = 8.0 Hz, 1H), 6.26 (s, 0.37H). 13C NMR (100 MHz, CDCl3): δ 157.3, 145.3, 141.3, 136.7, 133.9, 128.73, 128.67, 128.4, 127.3, 126.9, 126.4, 116.9, 116.7, 110.8, 78.9. HRMS-ESI(m/z): Calcd for C21H17D2N2 [M+H]+ 301.1668, Found: 301.1666.

2a-2-benzyl D. Silica gel column chromatography (hexane/AcOEt =3/1) gave 2a-2-benzyl D as a white solid (15 mg, 86 %), mp 134–135 °C; 1H NMR (400 MHz, CDCl3): δ 8.12 (s, 1H), 7.39–7.23 (m, 10H), 7.17 (dd, J = 7.4 and 8.4 Hz, 1H), 7.09 (d, J = 7.6 Hz, 1H), 6.63 (dd, J = 7.6 and 8.0 Hz, 1H), 6.50 (d, J = 8.0 Hz, 1H), 6.27 (s, 0.37H), 4.55 (d, J = 8.8 Hz, 1H), 4.17 (d, J = 8.0 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 157.5, 145.3, 141.3, 136.8, 133.9, 128.74, 128.67, 128.4, 127.3, 126.9, 126.4, 116.9, 116.7, 110.8, 78.9, 50.7. HRMS-ESI(m/z): Calcd for C21H18DN2 [M+H]+ 300.1606, Found: 300.1578.

1-benzyl-2-p-tolyl-1,2-dihydroquinazoline

(2b).

Silica

gel

column

chromatography

1

(hexane/AcOEt =4/1) gave 2b as a white solid (59 mg, 95 %), mp 149–151 °C; H NMR (400 MHz, CDCl3): δ 8.10 (s, 1H), 7.30–7.08 (m, 11H), 6.63 (dd, J = 7.6 and 7.2 Hz, 1H), 6.49 (d, J = 8.4 Hz, 1H), 13

6.21 (s, 1H), 4.54 (d, J = 16.4 Hz, 1H), 4.16 (d, J = 16.4 Hz, 1H), 2.32 (s, 3H). C NMR (100 MHz, CDCl3): δ 157.2, 145.3, 138.4, 138.1, 136.9, 133.8, 129.4, 128.7, 126.8, 126.3, 116.9, 110.8, 78.6, 50.3, 21.2. HRMS-ESI(m/z): Calcd for C22H21N2 [M+H]+ 313.1699, Found: 313.1693.

1-(4-methylbenzyl)-2-p-tolyl-1,2-dihydroquinazoline（2c）. Silica gel column chromatography (hexane/AcOEt =4/1) gave 2c as a white solid (48 mg, 73 %), mp 144–145 °C; 1H NMR (400 MHz, CDCl3): δ 8.09 (s, 1H), 7.30–7.08 (m, 10H), 6.61 (dd, J = 7.6 and 7.2 Hz, 1H), 6.49 (d, J = 8.4 Hz, 1H), 6.21 (s, 1H), 4.51 (d, J = 16.4 Hz, 1H), 4.11 (d, J = 16.4 Hz, 1H), 2.32 (s, 6H). 13C NMR (100 MHz, CDCl3): δ 157.1, 145.3, 138.4, 138.1, 136.9, 133.8, 133.7, 129.4, 129.37, 129.3, 128.6, 126.8, 126.3, 116.9, 110.8, 78.6, 50.3, 21.2, 21.1. HRMS-ESI(m/z): Calcd for C23H23N2 [M+H]+ 327.1856, Found: 327.1847.

1-(2-methylbenzyl)-2-phenyl-1,2-dihydroquinazoline （2 2d）. Silica gel column chromatography (hexane/AcOEt =3/1) gave 2d as a white solid (44 mg, 70 %), mp 153–155 °C; 1H NMR (400 MHz, CDCl3): δ 8.11 (s, 1H), 7.39–7.23 (m, 11H), 6.64 (dd, J = 7.6 and 7.6 Hz, 1H), 6.46 (d, J = 8.0 Hz, 1H), 6.18 (s, 1H), 4.54 (d, J = 16.8 Hz, 1H), 4.05 (d, J = 16.4 Hz, 1H), 2.23 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 157.3, 145.4, 141.3, 136.0, 134.0, 133.9, 130.5, 128.8, 128.7, 128.4, 127.3, 127.0, 126.3,


Page 9 of 16 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


126.2, 116.9, 116.6, 110.5, 78.2, 48.6, 19.1. HRMS-ESI(m/z): Calcd for C22H21N2 [M+H]+ 313.1699, Found: 313.1682.

2-phenyl-1-(2,4,6-trimethylbenzyl)-1,2-dihydroquinazoline （ 2e ） .

Silica

gel

column

chromatography (hexane/AcOEt =5/1) gave 2e as a white solid (50 mg, 74 %), mp 150–152 °C; 1H NMR (400 MHz, CDCl3): δ 7.98 (s, 1H), 7.35 (dd, J = 7.6 and 7.2 Hz, 1H), 7.25–7.07 (m, 5H), 7.08 (d, J = 7.2 Hz, 1H), 6.85 (d, J = 8.0 Hz, 1H), 6.82 (s, 2H), 6.69 (dd, J = 7.6 and 7.2 Hz, 1H), 5.79 (s, 1H), 4.55 (d, J = 13.2 Hz, 1H), 4.24 (d, J = 13.2 Hz, 1H), 2.27 (s, 3H), 2.04 (s, 6H). 13C NMR (100 MHz, CDCl3): δ 156.6, 146.2, 141.5, 138.3, 137.4, 133.8, 129.4, 128.6, 128.4, 128.0, 126.0, 117.9, 116.6, 110.5, 73.4, 45.2, 21.0, 19.7. Calcd for C24H25N2 [M+H]+ 341.2012, Found: 341.2020.

1-(4-methoxybenzyl)-2-phenyl-1,2-dihydroquinazoline（2 2f）. Silica gel column chromatography (hexane/AcOEt =4/1) gave 2f as a white solid (50 mg, 76 %), mp 135–136 °C; 1H NMR (400 MHz, CDCl3): δ 8.09 (s, 1H), 7.38–7.28 (m, 5H), 7.22–7.16 (m, 3H), 7.09 (d, J = 8.0 Hz, 1H), 6.83 (d, J = 8.8 Hz, 2H), 6.63 (dd, J = 7.6 and 7.2 Hz, 1H), 6.53 (d, J = 8.4 Hz, 1H), 6.23 (s, 1H), 4.51 (d, J = 16.4 Hz, 1H), 4.09 (d, J = 16.4 Hz, 1H), 3.78 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 158.9, 157.3, 145.3, 141.3, 133.8, 128.7, 128.6, 128.3, 128.1, 126.4, 117.0, 116.6, 114.1, 110.9, 78.6, 55.3, 50.2. HRMS-ESI(m/z): Calcd for C22H21N2O [M+H]+ 329.1648, Found: 329.1652.

1-(4-methoxybenzyl)-2-p-tolyl-1,2-dihydroquinazoline（2 2g）. Silica gel column chromatography (hexane/AcOEt =4/1) gave 2g as a white solid (48 mg, 70 %), mp 137–139 °C; 1H NMR (400 MHz, CDCl3): δ 8.12 (s, 1H), 7.26–7.09 (m, 9H), 6.83 (d, J = 7.2 Hz, 2H), 6.64 (dd, J = 7.2 and 7.2 Hz, 1H), 6.54 (d, J = 8.4 Hz, 1H), 6.20 (s, 1H), 4.52 (d, J = 16.4 Hz, 1H), 4.10 (d, J = 16.4 Hz, 1H), 3.78 (s, 3H), 2.31 (s, 3H).

13

C NMR (100 MHz, CDCl3): δ 158.9, 157.2, 145.4, 138.2, 134.0, 129.4, 128.7, 128.6,

128.2, 126.3, 116.9, 116.6, 114.1, 110.9, 78.1, 55.3, 50.1, 21.2. HRMS-ESI(m/z): Calcd for C23H23N2O [M+H]+ 343.1805, Found: 343.1795.

1-benzyl-2-(3-chlorophenyl)-1,2-dihydroquinazoline（2 2h）. Silica gel column chromatography (hexane/AcOEt =2/1) gave 2h as a white solid (50 mg, 75 %), mp 136–138 °C; 1H NMR (400 MHz, CDCl3): δ 8.12 (s, 1H), 7.37–7.11 (m, 10H), 7.11 (d, J = 7.6 Hz, 1H), 6.66 (dd, J = 7.2 and 7.6 Hz, 1H), 6.55 (d, J = 8.4 Hz, 1H), 6.23 (s, 1H), 4.59 (d, J = 16.8 Hz, 1H), 4.17 (d, J = 16.8 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 157.7, 144.9, 143.3, 136.5, 134.6, 134.1, 133.0, 128.83, 128.79, 128.5, 127.4, 126.9, 126.7, 124.6, 117.1, 111.0, 78.2, 51.0. HRMS-ESI(m/z): Calcd for C21H18ClN2 [M+H]+ 333.1153, Found: 333.1159.

1-(4-chlorobenzyl)-2-phenyl-1,2-dihydroquinazoline（2 2i）. Silica gel column chromatography (hexane/AcOEt =2/1) gave 2i as a white solid (33 mg, 50 %), mp 159–161 °C; 1H NMR (400 MHz, CDCl3): δ 8.12 (s, 1H), 7.37–7.16 (m, 10H), 7.11 (d, J = 7.6 Hz, 1H), 6.66 (dd, J = 7.6 and 6.8 Hz, 1H), 6.44 (d, J = 8.0 Hz, 1H), 6.22 (s, 1H), 4.49 (d, J = 16.8 Hz, 1H), 4.15 (d, J = 16.8 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 157.3, 145.0, 141.1, 135.4, 133.9, 133.0, 128.9, 128.8, 128.7, 128.5, 128.2, 126.4, 117.1, 117.0, 110.8, 79.1, 50.3. HRMS-ESI(m/z): Calcd for C21H18ClN2 [M+H]+ 333.1153, Found: 333.1127.



Page 10 of 16

2-(4-chlorophenyl)-1-(2,4,6-trimethylbenzyl)-1,2-dihydroquinazoline（2 2j）. Silica gel column chromatography (hexane/AcOEt =3/1) gave 2j as a white solid (59 mg, 79 %), mp 159–161 °C; 1H NMR (400 MHz, CDCl3): δ 7.99 (s, 1H), 7.35 (dd, J = 7.6 and 7.2 Hz, 1H), 7.25–7.07 (m, 5H), 7.08 (d, J = 7.2 Hz, 1H), 6.85 (d, J = 8.0 Hz, 1H), 6.82 (s, 2H), 6.69 (dd, J = 7.6 and 7.2 Hz, 1H), 5.76 (s, 1H), 4.55 (d, J = 13.2 Hz, 1H), 4.25 (d, J = 13.2 Hz, 1H), 2.27 (s, 3H), 2.06 (s, 6H). 13C NMR (100 MHz, CDCl3): δ 156.6, 146.2, 141.5, 138.3, 137.4, 133.8, 129.4, 128.6, 128.4, 128.0, 126.0, 117.9, 116.6, 110.5, 73.4, 45.2, 21.0, 19.7. Calcd for C24H24ClN2 [M+H]+ 375.1623, Found: 375.1637.

1-(3-fluorobenzyl)-2-phenyl-1,2-dihydroquinazoline（2 2k）. Silica gel column chromatography (hexane/AcOEt =2/1) gave 2k as a white solid (40 mg, 63 %), mp 149–151 °C; 1H NMR (400 MHz, CDCl3): δ 8.12 (s, 1H), 7.36–7.29 (m, 5H), 7.20–7.16 (m, 2H), 7.12 (d, J = 7.6 Hz, 1H), 7.03 (d, J = 7.6 Hz, 1H), 6.96–6.90 (m, 2H), 6.66 (dd, J = 6.8 and 7.6 Hz, 1H), 6.45 (d, J = 8.4 Hz, 1H), 6.24 (s, 1H), 4.51 (d, J = 16.8 Hz, 1H), 4.18 (d, J = 17.2 Hz, 1H).

13

C NMR (100 MHz, CDCl3): δ 157.3, 145.0,

141.1, 139.8 (d, J = 6.7 Hz), 133.9, 130.2 (d, J = 8.0 Hz), 128.8, 128.7, 128.5, 126.4, 122.3 (d, J = 2.8 Hz), 117.1, 117.0, 114.2 (d, J = 21.2 Hz), 113.7 (d, J = 21.9 Hz), 110.8, 79.1, 50.5. 19F NMR (CDCl3): δ -110.8, -112.6. Calcd for C21H18FN2 [M+H]+ 317.1449, Found: 317.1447. 1-benzyl-2-(3-fluorophenyl)-1,2-dihydroquinazoline （ 2l ） . Silica gel column chromatography (hexane/AcOEt =3/1) gave 2l as a white solid (43 mg, 68 %), mp 147–179 °C; 1H NMR (400 MHz, CDCl3): δ 8.12 (s, 1H), 7.38–7.09 (m, 11H), 6.66–6.61 (m, 1H), 6.55–6.49 (m, 1H), 6.24 (s, 1H), 4.55 (d, J = 16.8 Hz, 1H), 4.17 (d, J = 17.2 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 157.5 (d, J = 39.2 Hz), 145.1 (d, J = 21.9 Hz), 141.3, 136.7 (d, J = 23.4 Hz), 134.0 (d, J = 18.7 Hz), 130.2(d, J = 8.0 Hz), 128.8, 128.72, 128.66, 128.4, 127.4 (d, J = 12.8 Hz), 126.9 (d, J = 3.2 Hz), 126.4, 122.0(d, J = 2.9 Hz), 117.0(d, J = 18.4 Hz), 116.7, 115.2 (d, J = 21.2 Hz), 113.4 (d, J = 21.7 Hz), 110.9 (d, J = 25.2 Hz), 78.9, 50.9 (d, J = 25.0 Hz).

19

F NMR(CDCl3): δ -111.0, -112.2. Calcd for C21H18FN2 [M+H]+ 317.1449,

Found: 317.1454.

1-(4-nitrobenzyl)-2-phenyl-1,2-dihydroquinazoline （2 2m）. Silica gel column chromatography (hexane/AcOEt =2/1) gave 2m as a white solid (30 mg, 44 %), mp 153–155 °C; 1H NMR (400 MHz, CDCl3): δ 8.19 (s, 1H), 8.18 (d, J = 7.6 Hz, 4H), 7.55 (d, J = 8.4 Hz, 2H), 7.43 (d, J = 8.8 Hz, 2H), 7.26-7.20 (m, 2H), 7.19 (d, J = 7.6 Hz, 1H), 6.77 (dd, J = 7.2 and 6.8 Hz, 1H), 6.48 (d, J = 8.4 Hz, 1H), 6.34 (s, 1H), 4.70 (d, J = 17.2 Hz, 1H), 4.32 (d, J = 17.2 Hz, 1H).

13

C NMR (100 MHz, CDCl3): δ

158.3, 153.0.0, 144.2, 134.5, 129.2, 127.5, 127.3, 124.20, 124.18, 121.0, 118.6, 111.4, 78.4, 51.2. HRMS-ESI(m/z): Calcd for C21H18N3O2 [M+H]+ : 344.1394, Found: 344.1391.

1-methyl-2-phenyl-1,2-dihydroquinazoline （ 2n ） . Silica gel column chromatography (hexane/AcOEt =4/1) gave 2n as a white solid (29 mg, 65 %), mp 140–142 °C; 1H NMR (400 MHz, CDCl3): δ 8.08 (s, 1H), 7.38–7.28 (m, 6H), 7.05 (d, J = 7.6 Hz, 1H), 6.61 (dd, J = 7.6 and 6.8 Hz, 2H), 6.51 (d, J = 6.8 Hz, 1H), 6.15 (s, 1H), 2.76 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 157.1, 145.9, 140.7, 134.1, 128.7, 128.42, 128.36, 126.2, 116.5, 109.8, 80.2,34.4. Calcd for C15H15N2 [M+H]+ 223.1230, Found: 223.1260.


Page 11 of 16 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


2-(3-fluorophenyl)-1-methyl-1,2-dihydroquinazoline（2 2o）. Silica gel column chromatography (hexane/AcOEt =2/1) gave 2z as a white solid (40 mg, 83 %), mp 145–147 °C; 1H NMR (400 MHz, CDCl3): δ 8.08 (s, 1H), 7.32–7.28 (m, 2H), 7.14 (d, J = 7.6 Hz, 1H), 7.10–7.04 (m, 2H),6.98 (dd, J = 8.0 and 8.4 Hz, 1H), 6.67 (dd, J = 7.2 and 7.2 Hz, 1H), 6.53 (d, J = 8.4 Hz, 1H), 6.14 (s, 1H), 2.78 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 163.5 (d, J = 163.8 Hz), 157.4, 145.6, 143.4 (d, J = 3.7 Hz), 134.2, 130.3 (d, J = 5.5 Hz), 128.5, 121.8, 116.8, 116.4, 115.2 (d, J = 13.9 Hz), 113.2 (d, J = 14.5 Hz), 110.0, 79.7, 34.5. Calcd for C15H15N2 [M+H]+ 223.1230, Found: 223.1260.

1-ethyl-2-phenyl-1,2-dihydroquinazoline（2p）. Silica gel column chromatography (hexane/AcOEt =4/1) gave 2p as a white solid (38 mg, 80 %), mp 142–144 °C; 1H NMR (400 MHz, CDCl3): δ 8.00 (s, 1H), 7.40 (d, J = 8.0 Hz, 2H), 7.33–7.24 (m, 4H), 7.07 (d, J = 7.6 Hz, 1H), 6.65 (dd, J = 7.2 and 7.2 Hz, 2H), 6.20 (s, 1H), 3.32 (q, J = 7.2 Hz, 1H), 3.14 (q, J = 7.2 Hz, 1H), 1.08 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 156.9, 144.9, 142.6, 133.8, 128.8, 128.6, 128.2, 126.3, 116.6, 116.0, 110.0, 78.8,42.5, 12.1. Calcd for C15H15N2 [M+H]+ 223.1230, Found: 223.1260.

6-methoxy-1-methyl-2-phenyl-1,2-dihydroquinazoline（2 2q）. Silica gel column chromatography (hexane/AcOEt =4/1) gave 2q as a white solid (33 mg, 66 %), mp 175–177 °C; 1H NMR (400 MHz, CDCl3): δ 8.08 (s, 1H), 7.34–7.26 (m, 5H), 6.91(dd, J = 8.8 and 8.8 Hz, 1H), 6.69 (s, 1H), 6.48 (d, J = 8.8 Hz, 1H), 6.55 (s, 1H), 3.76 (s, 3H), 2.74 (s, 3H).

13

C NMR (100 MHz, CDCl3): δ 157.0, 151.2,

140.7, 141.4, 128.6, 128.3, 126.3, 120.4, 117.3, 112.9, 111.3, 80.1, 55.9, 34.7. Calcd for C16H17N2O [M+H]+ 253.1335, Found: 253.1360.

2-(4-chlorophenyl)-6-methoxy-1-methyl-1,2-dihydroquinazoline （ 2r ） . Silica gel column chromatography (hexane/AcOEt =3/1) gave 2r as a white solid (41 mg, 71 %), mp 172–174 °C; 1H NMR (400 MHz, CDCl3): δ 8.08 (s, 1H), 7.34–7.26 (br, 4H), 6.93(dd, J = 8.8 and 8.8 Hz, 1H), 6.70 (s, 1H), 6.49 (d, J = 8.8 Hz, 1H), 6.02 (s, 1H), 3.77 (s, 3H), 2.74 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 157.3, 151.4, 138.9, 134.0, 130.5, 128.8, 127.8, 120.6, 112.9, 111.6, 79.4, 55.9, 34.7. Calcd for C16H16ClN2O [M+H]+ 287.0946, Found: 287.0954.

6-(benzyloxy)-1-methyl-2-phenyl-1,2-dihydroquinazoline （ 2s ） .

Silica

gel

column

chromatography (hexane/AcOEt =4/1) gave 2s as a white solid (39 mg, 60 %), mp 142–144 °C; 1H NMR (400 MHz, CDCl3): δ 8.06 (s, 1H), 7.44–7.28 (m, 10H), 6.98(dd, J = 8.8 and 2.8 Hz, 1H), 6.81 (d, J = 3.2 Hz, 1H), 6.47 (d, J = 8.8 Hz, 1H), 6.05 (s, 1H), 5.00 (s, 2 H), 2.74 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 156.9, 150.4, 140.5, 137.2, 128.7, 128.62, 128.59, 128.3, 128.0, 127.5, 126.3, 121.6, 117.3, 114.4, 111.2, 80.1, 71.0, 34.6. Calcd for C22H21N2O [M+H]+ 329.1648, Found: 329.1659.

1-benzyl-6-(benzyloxy)-2-(4-chlorophenyl)-1,2-dihydroquinazoline（2 2t ） . Silica gel column chromatography (hexane/AcOEt =2/1) gave 2t as a white solid (70 mg, 80 %), mp 148–150 °C; 1H NMR (400 MHz, CDCl3): δ 8.14 (s, 1H), 7.46–7.27 (m, 14H), 6.93(dd, J = 8.8 and 2.8 Hz, 1H), 6.81 (d, J = 3.2 Hz, 1H), 6.53 (d, J = 8.8 Hz, 1H), 6.19 (s, 1H), 5.01 (s, 2 H), 4.55 (d, J = 16.4 Hz, 1H), 4.20 (d, J = 16.4Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 157.4, 150.8, 139.7, 139.5, 137.0, 134.0, 128.8, 128.6, 128.1, 128.0, 127.5, 127.4, 127.0, 121.5, 118.0, 114.1, 113.1, 77.8, 70.8, 51.9. Calcd for C28H24ClN2O [M+H]+ 439.1572, Found: 439.1615.



6-bromo-1-methyl-2-phenyl-1,2-dihydroquinazoline（2 2u）. Silica gel column chromatography (hexane/AcOEt =3/1) gave 2u as a white solid (52 mg, 86 %), mp 158–160 °C; 1H NMR (400 MHz, CDCl3): δ 8.01 (s, 1H), 7.36–7.31 (m, 6H), 7.17(s, 1H), 6.39 (d, J = 8.4 Hz, 1H), 6.14 (s, 1H), 2.74 (s, 3H).

13

C NMR (100 MHz, CDCl3): δ 155.7, 144.8, 140.2, 136.4, 130.6, 128.8, 128.6, 126.1, 117.8,

111.7, 108.0, 80.3, 34.5. Calcd for C15H14BrN2 [M+H]+ 301.0335, Found: 301.0315.

1-benzyl-6-bromo-2-phenyl-1,2-dihydroquinazoline（2 2v）. Silica gel column chromatography (hexane/AcOEt =2/1) gave 2v as a white solid (49 mg, 65 %), mp 152–154 °C; 1H NMR (400 MHz, CDCl3): δ 8.06 (s, 1H), 7.36–7.20 (m, 12H), 6.38 (d, J = 8.8 Hz, 1H), 6.27 (s, 1H), 4.50 (d, J = 16.8 Hz, 1H), 4.18 (d, J = 16.8Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 155.7, 144.1, 139.2, 136.3, 136.2，130.9, 128.8, 128.6, 127.5, 126.8, 126.3, 118.3, 112.8, 108.3, 79.1, 50.9. Calcd for C21H18BrN2 [M+H]+ 377.0648, 379.0633 Found: 377.0679, 379.0654.

1-benzyl-6-bromo-2-p-tolyl-1,2-dihydroquinazoline（2 2w）. Silica gel column chromatography (hexane/AcOEt =2/1) gave 2w as a white solid (41 mg, 52 %), mp 140–142 °C; 1H NMR (400 MHz, CDCl3): δ 8.04 (s, 1H), 7.43 (d, J = 8.4 Hz, 1H), 7.30–7.11 (m, 10H), 6.36 (d, J = 8.8 Hz, 1H), 6.23 (s, 1H), 4.48 (d, J = 16.8 Hz, 1H), 4.17 (d, J = 16.4Hz, 1H), 2.33 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 144.1, 142.3, 139.9, 138.5, 136.2, 133.8, 130.9, 129.5, 128.8, 127.5, 126.8, 126.2, 122.1, 112.8, 78.8, 50.7, 29.7. Calcd for C22H20BrN2 [M+H]+ 391.0804, Found: 391.0824.

6-bromo-1-(2-methylbenzyl)-2-phenyl-1,2-dihydroquinazoline （ 2x ） . Silica gel column chromatography (hexane/AcOEt =2/1) gave 2x as a white solid (63 mg, 81 %), mp 169–171 °C; 1H NMR (400 MHz, CDCl3): δ 8.05 (s, 1H), 7.35–7.11 (m, 11H), 6.34 (d, J = 8.8 Hz, 1H), 6.19 (s, 1H), 4.49 (d, J = 16.8 Hz, 1H), 4.05 (d, J = 16.8Hz, 1H), 2.25 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 155.9, 144.2, 140.8, 136.4, 136.0, 133.3, 131.0, 130.7, 128.9, 128.6, 127.5, 126.9, 126.3, 118.2, 112.5, 108.2, 78.3, 48.7, 19.1. Calcd for C22H20BrN2 [M+H]+ 391.0804, Found: 391.0803.

6-bromo-1-(4-chlorobenzyl)-2-phenyl-1,2-dihydroquinazoline （ 2y ） . Silica gel column chromatography (hexane/AcOEt =2/1) gave 2y as a white solid (59 mg, 72 %), mp 163–164 °C; 1H NMR (400 MHz, CDCl3): δ 8.06 (s, 1H), 7.35–7.14 (m, 11H), 6.32 (d, J = 8.8 Hz, 1H), 6.23 (s, 1H), 4.45 (d, J = 16.4 Hz, 1H), 4.16 (d, J = 16.8Hz, 1H).

13

C NMR (100 MHz, CDCl3): δ 155.9, 143.8,

140.6, 136.3, 134.8, 133.2, 131.0, 129.0, 128.9, 128.7, 128.1, 126.3, 118.4, 112.8, 108.7, 79.2, 50.5. HRMS-ESI(m/z): Calcd for C21H17BrClN2 [M+H]+ 411.0258, 413.0243, Found: 411.0304, 413.0277.

1-benzyl-6-bromo-2-(4-bromophenyl)-1,2-dihydroquinazoline （ 2z ） . Silica gel column chromatography (hexane/AcOEt =2/1) gave 2z as a white solid (80 mg, 88 %), mp 163–164 °C; 1H NMR (400 MHz, CDCl3): δ 8.05 (s, 1H), 7.43 (d, J = 8.4 Hz, 1H), 7.33–7.21 (m, 10H), 6.41 (d, J = 8.8 Hz, 1H), 6.21 (s, 1H), 4.51 (d, J = 16.8 Hz, 1H), 4.15 (d, J = 16.4Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 156.2, 143.8, 139.7, 136.5, 136.0, 131.9, 131.0, 128.9, 128.1, 127.6, 126.8, 122.6, 118.3, 113.1, 108.7, 78.3, 51.1. Calcd for C21H17Br2N2 [M+H]+ 454.9753, Found: 454.9730

(E)-1-benzyl-2-styryl-1,2-dihydroquinazoline （ 3a ） . Silica gel column chromatography (hexane/AcOEt =3/1) gave 3a as a white solid (46 mg, 71 %), mp 160–162 °C; 1H NMR (400 MHz,


Page 12 of 16

Page 13 of 16 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


CDCl3): δ 8.14 (s, 1H), 7.35–7.14 (m, 10H), 6.68 (dd, J = 6.8 and 7.2 Hz, 1H), 6.56 (d, J = 15.6 Hz, 1H), 6.33 (d, J = 8.4 Hz, 1H), 6.32 (dd, J = 15.6 and 7.6 Hz, 1H), 5.66 (d, J = 7.6 Hz, 1H), 4.57 (d, J = 16.0 Hz, 1H), 4.34 (d, J = 16.4 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 158.4, 145.0, 137.1, 136.2, 133.6, 131.8, 128.8, 128.6, 128.5, 128.0, 127.4, 126.8, 125.5, 117.8, 117.1, 111.7, 77.4, 50.7. HRMS-ESI(m/z): Calcd for C23H21N2 [M+H]+ 325.1699, Found: 325.1724. ■ ASSOCIATED CONTENT Supporting Information The Supporting Information is available free of charge on the ACS Publications website at DOI:. Copies of 1H NMR,

13C

NMR, and

19F

NMR spectra for all new products (PDF)

■ AUTHOR INFORMATION Corresponding Author *E-mail: [email protected]. *E-mail: [email protected]. *E-mail: [email protected].

Notes The authors declare no competing ﬁnancial interest.

■ ACKNOWLEDGMENTS ACKNOWLEDGMENTS We gratefully acknowledge financial support from SKLUWRE (No.2017TS01).

■ REFERENCES (1) Michael, J. P. Quinoline, Quinazoline and Acridone Alkaloids. Nat. Prod. Rep. 2004, 21, 650–668. (2) Ellsworth, E. L.; Tran, T. P.; Showalter, H. D. H.; Sanchez, J. P.; Watson, B. M.; Stier, M. A.; Domagala, J. M.; Gracheck, S. J.; Joannides, E. T.; Shapiro, M. A.; Dunham, S. A.; Hanna, D. L.; Huband, M. D.; Gage, J. W.; Bronstein, J. C. Liu, J. Y.; Nguyen, D. Q.; Singh, R. 3-Aminoquinazolinediones as a New Class of Antibacterial Agents Demonstrating Excellent Antibacterial Activity Against Wild-Type and Multidrug Resistant Organisms. J. Med. Chem., 2006, 49, 6435–6438. (3) (a) Doyle, L. A.; Ross, D. D. Multidrug Resistance Mediated by the Breast Cancer Resistance Protein BCRP (ABCG2). Oncogene, 2003, 2003 22, 7340–7358. (b) Ma, Z. Z.; Hano, Y.; Nomura, T.; Chen, Y. J. Two New Pyrroloquinzolinoquinoline Alkaloids from Peganum nigellastrum. Heterocycles 1997, 1997 46, 541–546. (c) Kang, H. B.; Rim, H.-K.; Park, J. Y.; Choi, H. W.; Choi, D. L.



Seo, J.-H.; Chung, K.-S.; Huh, G.; Kim, J.; Choo, D. J.; Lee, K.-T.; Lee, J. Y. In Vivo Evaluation of Oral Anti-tumoral Effect of 3,4-Dihydroquinazoline Derivative on Solid Tumor. Bioorg. Med. Chem. Lett., 2012, 2012 22, 1198–1201. (4) Chien, T.-C.; Chen, C.-S.; Yu, F.-H.; Chern, J.-W. Nucleosides XI. Synthesis and Antiviral Evaluation of 5'-Alkylthio-5'-deoxy Quinazolinone Nucleoside Derivatives as S-Adenosyl-L-homocysteine Analogs. Chem. Pharm. Bull., 2004, 2004 52, 1422–1426. (5) Al-Shamma, A.; Drake, S.; Flynn, D. L.; Mitscher, L. A.; Park, Y. H.; Rao, G. S. R.; Simpson, A.; Swayze, J. K.; Veysoglu, T.; Wu, S. T.-S. Antimicrobial Agents from Higher Plants. Antimicrobial Agents From Peganum harmala Seeds. J. Nat. Prod. 1981, 1981 44, 745–747. (6) (a) Kobayashi, S.; Ueno, M.; Suzuki, R.; Ishitani, H. Catalytic Asymmetric Synthesis of Febrifugine and Isofebrifugine.Tetrahedron Lett. 1999, 40, 40 2175–2178. (b) Verhaeghe, P.; Azas, N.; Gasquet, M.; Hutter, S.; Ducros, C.; Laget, M.; Rault, S.; Rathelot, P.; Vanelle, P. Synthesis and Antiplasmodial Activity of New 4-Aryl-2-trichloromethylquinazolines. Bioorg. Med. Chem. Lett., 2008, 2008 18, 396–401. (7) (a) Seo, H. N.; Choi, J. Y.; Choe, Y. J.; Kim, Y.; Rhim, H.; Lee, S. H.; Kim, J.; Joo, D. J.; Lee, J. Y. Discovery of Potent T-Type Calcium Channel Blocker. Bioorg. Med. Chem. Lett., 2007, 2007 17, 5740–5743. (b) Rhim, H.; Lee, Y. S.; Park, S. J.; Chung, B. Y.; Lee, J. Y. Synthesis and 2+ Biological Activity of 3,4-Dihydroquinazolines for Selective T-Type Ca Channel Blockers. Bioorg. Med. Chem. Lett., 2005, 2005 15, 283–286. (c) Lee, Y. S.; Lee, B. H.; Park, S. J.; Kang, S. B.; Rhim, H. Park, J.-Y.; Lee, J.-H.; Jeong, S.-W.; Lee, J. Y. 3,4-Dihydroquinazoline Derivatives as 2+ Novel Selective T-type Ca Channel Blockers.Bioorg. Med. Chem. Lett., 2004, 2004 14, 3379–3384. (d) Jeong, J. A.; Cho, H.; Jung, S. Y.; Kang, H. B.; Park, J. Y.; Kim, J.; Choo, D. J.; Lee, J. Y. 3D QSAR Studies on 3,4-Dihydroquinazolines as T-Type Calcium Channel Blocker by Comparative Molecular Similarity Indices Analysis (CoMSIA). Bioorg. Med. Chem. Lett., 2010, 2010 20, 38–41. (8) Patterson, S.; Alphey, M. S.; Jones, D. C.; Shanks, E. J.; Street, I. P.; Frearson, J. A.; Wyatt, P. G.; Gilbert, I. H.; Fairlamb, A. H. Dihydroquinazolines as a Novel Class of Trypanosoma bruceiTrypanothione Reductase Inhibitors: Discovery, Synthesis, and Characterization of their Binding Mode by Protein Crystallography. J. Med. Chem. 2011, 54, 6514–6530. (9) For selected examples on the synthesis of dihydroquinazolines, see: (a) Movassaghi, M.; Hill, M. D. Single-Step Synthesis of Pyrimidine Derivatives. J Am Chem Soc. 2006, 2006 128, 14254–14255. (b) Sarma, R.; Prajapati, D. Microwave-promoted Efficient Synthesis of Dihydroquinazolines. Green Chem. 2011, 2011 13, 718–722. (c) Wiedemann, S. H.; Ellman, J. A.; Bergman, R. G. Rhodium-Catalyzed Direct C−H Addition of 3,4-Dihydroquinazolines to Alkenes and Their Use in the Total Synthesis of Vasicoline. J. Org. Chem. 2006, 2006 71, 1969–1976; (d) Rohlmann, R.; Stopka, T. Richter, H.; Mancheño, O. G. Iron-catalyzed Oxidative Tandem Reactions with TEMPO Oxoammonium Salts: Synthesis of Dihydroquinazolines and Quinolines. J. Org. Chem. 2013, 2013 78, 6050–6064. (e) Luo, L.; Zhao, X.; Zhang, L.; Yuan, Y.; Lü, S.; Jia, X. An Aerobic Oxidative Aza-[4+2] Cycloaddition Induced by Radical Cation Salt: Synthesis of Dihydroquinazoline Derivatives.Tetrahedron Lett. 2016, 2016 57, 5830–5833. (f). Portela-Cubillo, F.; Scott, J. S.; Walton, J. C. Microwave-Promoted Syntheses of Quinazolines and Dihydroquinazolines from 2-Aminoarylalkanone O-Phenyl Oximes. J. Org. Chem., 2009, 2009 74, 4934–4942. (g) McGowan, M. A.; McAvoy, C. Z.; Buchwald, S. L. Palladium-Catalyzed N-Monoarylation of Amidines and a One-Pot Synthesis of Quinazoline Derivatives. Org. Lett. 2012, 2012 14, 3800–3803. (10) (a) Bourissou, D.; Guerret, O.; Gabbaϊ, F. P.; Bertrand, G. Stable Carbenes.Chem. Rev. 2000, 2000 100, 39–92. (b) Herrmann, W. A. N-Heterocyclic Carbenes: a New Concept in Organometallic Catalysis. Angew. Chem. Int. Ed. 2002, 2002 41, 1290–1309. (c) César, V.; Bellemin-Laponnaz, S.; Gade, L. H.; Chiral N-Heterocyclic Carbenes as Stereodirecting Ligands in Asymmetric Catalysis. Chem. Soc. Rev. 2004, 2004 33, 619–636. (d) Hopkinson, M. N.; Richter, C.; Schedler, M.; Glorius, F. An Overview of N-Heterocyclic Carbenes. Nature 2014, 2014 510, 485–496. (11) (a) Igau, A.; Grutzmacher, H.; Baceiredo, A.; Bertrand, G. Analogous α,α’-Biscarbenoid Triply Bonded Species: Synthesis of a Stable λ3-Phosphinocarbene-λ5-phosphaacetylene. J. Am. Chem. Soc. 1988, 1988 110, 6463–6466. (b) Arduengo III, A. J.; Harlow, R. L.; Kline, M. A Stable Crystalline Carbene. J. Am. Chem. Soc. 1991, 1991 113, 361–363. (12) (a) Díez-González, S.; Marion, N.; Nolan, S. P. N-Heterocyclic Carbenes in Late Transition Metal Catalysis. Chem. Rev. 2009, 2009 109, 3612–3676. (b) Fortman, G. C.; Nolan, S. P. N-Heterocyclic Carbene (NHC) Ligands and Palladium in Homogeneous Cross-coupling Catalysis: a Perfect Union. Chem. Soc. Rev. 2011, 2011 40, 5151–5169. (c) Enders, D.; Niemeier, O.; Henseler, A. Organocatalysis by N-Heterocyclic Carbenes. Chem. Rev. 2007, 2007 107, 5606–5655. (13) For selected examples of NHCs as ligand for Suzuki-Miyaura coupling, see: (a) Gstöttmayr, C. W. K.; Böhm, V. P. W.; Herdweck, E.; Grosche, M.; Herrmann, W. A. A Defined N‐Heterocyclic Carbene Complex for the Palladium‐Catalyzed Suzuki Cross‐Coupling of Aryl Chlorides at Ambient Temperatures. Angew. Chem. Int. Ed. 2002, 2002 41, 1363–1365. (b) Altenhoff, G.; Goddard, R.; Lehmann, C. W.; Glorius, F. An N-Heterocyclic Carbene Ligand with Flexible Steric Bulk Allows Suzuki Cross-Coupling of Sterically Hindered Aryl Chlorides at Room Temperature. Angew. Chem. Int. Ed. 2003, 42, 3690–3693. (c) Lebel, H.; Janes, M. K.; Charette, A. B.; Nolan, S. P. Structure and Reactivity of "Unusual" N-Heterocyclic Carbene (Nhc) Palladium Complexes Synthesized from Imidazolium Salts. J. Am. Chem. Soc. 2004, 126, 5046–5047. (d) Zeng, F.; Yu,


Page 14 of 16

Page 15 of 16 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


A. Pyridyl-Supported Pyrazolyl−N-Heterocyclic Carbene Ligands and the Catalytic Activity of Their Palladium Complexes in Suzuki−Miyaura Reactions. J. Org. Chem. 2006, 2006 71, 5274–5281. (14) For selected examples of NHCs as ligand for Heck reaction, see: (a) Yang, C.; Lee, H. M.; Nolan, S. P. Highly Efficient Heck Reactions of Aryl Bromides with n-Butyl Acrylate Mediated by a Palladium/Phosphine−Imidazolium Salt System. Org. Lett. 2001, 2001 3, 1511–1514. (b) Tsoureas, N.; Danopoulos, A. A.; Tulloch, A. A. D.; Light, M. E. (Diphenylphosphino)alkyl-Functionalized Nucleophilic Carbene Complexes of Palladium. Organometallics 2003, 2003 22, 4750–4758. (c) Wang, R.; Twamley, B.; Shreeve, J. M. A Highly Efficient, Recyclable Catalyst for C−C Coupling Reactions in Ionic Liquids: Pyrazolyl-Functionalized N-Heterocyclic Carbene Complex of Palladium(II). J. Org. Chem. 2006, 2006 71, 426–429. (15) Nelson, D. J.; Nolan, S. P. Quantifying and Understanding the Electronic Properties of N-Heterocyclic Carbenes. Chem. Soc. Rev. 2013, 2013 42, 6723–6753. (16) For reviews, see: (a) Schuster, O.; Yang, L.; Raubenheimer, H. G.; Albrecht, M. Beyond Conventional N-Heterocyclic Carbenes: Abnormal, Remote, and Other Classes of NHC Ligands with Reduced Heteroatom Stabilization. Chem. Rev. 2009, 2009 109, 3445–3478. (b) Soleilhavoup, M.; Bertrand, G. Cyclic (Alkyl)(Amino)Carbenes (CAACs): Stable Carbenes on the Rise. Acc. Chem. Res. 2015, 2015 48, 256–266. (17) For selected examples: (a) Lavallo, V.; Canac, Y.; Präsang, C.; Donnadieu, B.; Bertrand, G. Stable Cyclic (Alkyl)(amino)carbenes as Rigid or Flexible, Bulky, Electron-rich Ligands for Transition-metal Catalysts: a Quaternary Carbon Atom Makes the Difference. Angew. Chem. Int. Ed. 2005, 2005 44, 5705–5709. (b) Jazzar, R.; Dewhurst, R. D.; Bourg, J. B.; Donnadieu, B.; Canac , Y.; Bertrand, G. Intramolecular “Hydroiminiumation” of Alkenes: Application to the Synthesis of Conjugate Acids of Cyclic Alkyl Amino Carbenes (CAACs). Angew. Chem. Int. Ed. 2007, 2007 46, 2899–2902. (c) Rao, B.; Tang, H.; Zeng, X.; Liu, L.; Melaimi, M.; Bertrand, G. Cyclic (Amino)(aryl)carbenes (CAArCs) as Strong σ‐Donating and π‐Accepting Ligands for Transition Metals. Angew. Chem. Int. Ed. 2015, 2015 54, 14915–14919. (18) (a) Jothibasu, R.; Huynh, H. V. Versatile Coordination Chemistry of Indazole-derived Carbenes.Chem. Commun. 2010, 46, 2986–2988. (b) Sivaram, H.; Jothibasu, R.; Huynh, H. V. Gold Complexes of an Alicyclic Indazole-Derived N-Heterocyclic Carbene: Syntheses, Characterizations, and Ligand Disproportionation. Organometallics 2012, 2012 31, 1195–1203. (c) Zhou, Y.; Liu, Q.; Lv, W.; Pang, Q.; Ben, R.; Qian, Y.; Zhao, J. Indazolin-s-ylidene–N-Heterocyclic Carbene Complexes of Rhodium, Palladium, and Gold: Synthesis, Characterization, and Catalytic Hydration of Alkynes. Organometallics 2013, 2013 32, 3753–3759. (d) Bernhammer, J. C.; Chong, N.; Jothibasu, R.; Zhou, B.; Huynh, H. V. Palladium(II) Complexes Bearing an Indazole-Derived N-Heterocyclic Carbene and Phosphine Coligands as Catalysts for the Sonogashira Coupling and the Hydroamination of Alkynes.Organometallics 2014, 2014 33, 3607–3617. (e) Bernhammer, J. C.; Singh, H.; Huynh, H. V. Amine-Functionalized Indazolin-3-ylidene Complexes of Palladium(II) by Postmodification of a Single Precursor. Organometallics 2014, 2014 33, 4295–4301. (19) Chen, Q.; Mao, Z.; Guo, F.; Liu, X. Indazolium Halides as Efficient Ligands for Pd-Catalyzed Suzuki–Miyaura Cross-coupling of Aryl Bromides with Arylboronic Acids. Tetrahedron Lett. 2016, 2016 57, 3735–3738. (20) Molecular rearrangements in organic synthesis (Eds.: Rojas C. M.), Wiley-VCH, Weinheim, 2015. (21) For selected examples of N-N cleavage in organic synthesis, see: (a) Kiernicki, J. J.; Zeller,M.; Szymczak, N. K. Hydrazine Capture and N-N Bond Cleavage at Iron Enabled by Flexible Appended Lewis Acids. J. Am. Chem. Soc. 2017, 2017 139, 18194–18197. (b) Tang, C.; Liang, Q.; Jupp, A. R.; Johnstone, T. C.; Neu, R. C.; Song, D.; Grimme, S.; Stephan, D. W. 1,1-Hydroboration and a Borane Adduct of Diphenyldiazomethane: A Potential Prelude to FLP-N2 Chemistry. Angew. Chem. Int. Ed. 2017 2017, 17 56, 16588–16592. (c) Chen, Q.; Liu, X.; Guo, F.; Chen, Z. An Unexpected Rearrangement of Pyrazolium Halides Based on N–N Bond Cleavage: Synthesis of 1,2-Dihydropyrimidines. Chem. Commun. 2017 2017, 53, 6792–6795 and references cited therein. (22) (a) Melen, R. L. A Step Closer to Metal‐Free Dinitrogen Activation: A New Chapter in the Chemistry of Frustrated Lewis Pairs. Angew. Chem. Int. Ed. 2018 2018, 18 57, 880–882. (b) Milsmann, C.; Turner, Z. R.; Semproni, S. P.; Chirik, P. J. Azo N-N Bond Cleavage with a Redox-active Vanadium Compound Involving Metal–ligand Cooperativity. Angew. Chem. Int. Ed. 2012, 2012 51, 5386–5390. (c) Hidai, M.; Mizobe, Y. Recent Advances in the Chemistry of Dinitrogen Complexes.Chem. Rev. 1995, 1995 95, 1115–1133. (d) MacKay, B. A.; Fryzuk, M. D. Dinitrogen Coordination Chemistry: on the Biomimetic Borderlands. Chem. Rev. 2004, 2004 104, 385–402. (23) (a) Guan, Z.; Nieger, M.; Schmidt, A. Organic Synthesis with N‐Heterocyclic Carbenes of Indazole: Synthesis of Benzo(thio)imidates, Benzo[d][1,3]thiazines and Quinazoline‐4‐thiones. Eur. J. Org. Chem. 2015, 2015 4710–4719. (b) Guan, Z.; Hillrichs, K.; Ünlü, C.; Rissanen, K.; Nieger, M.; Schmidt, A. Synthesis of 2-Anilinobenzimidates, Anthranilamides, and 2,3-Dihydroquinazolin-4(1H)-ones from N-Heterocyclic Carbenes of Indazole. Tetrahedron 2015, 2015 71, 276–282. (c) Guan, Z.; Nieger, M.; Schmidt, A. Syntheses of Acridines and Quinazoline-2,4(1H,3H)-dithiones by Rearrangements of N-Heterocyclic Carbenes of Indazole. Heterocycles 2014, 2014 89, 2356–2367. (d) Guan, Z.; Wiechmann, S.; Drafz, M.; Hübner, E.; Schmidt, A. Pericyclic Rearrangements of N-Heterocyclic Carbenes of Indazole to Substituted



9-Aminoacridines. Org. Biomol. Chem. 2013, 2013 11, 3558–3567. (e) Schmidt, A.; Münster, N.; Dreger, A. Functionalized 4-Aminoquinolines by Rearrangement of Pyrazole N-Heterocyclic Carbenes. Angew. Chem. Int. Ed. 2010, 2010 49, 2790–2793. (f) Dreger, A.; Cisneros Camuña, R.; Münster, N.; Rokob, T. A. Pápai, I.; Schmidt, A. Rearrangements of N‐Heterocyclic Carbenes of Pyrazole to 4‐Aminoquinolines and Benzoquinolines. Eur. J. Org. Chem. 2010, 2010 4296–4305; (24) Note: The nitrogen in 1a was numbered as 1 and 2 as shown in scheme 3 according to the rules of nomenclature, however, the number of position in the keteneimine B was expediently assigned 1, 3, and 5’ according to possible shift rearrangement. (25) The exact reason for a lower deuterated ratio of 4a-2-benzyl D is not so clear at present. The 4a deuterated ratio did not further be reduced when used the product 2a-2-benzyl D (58-64%) as substrate under the reaction condition. (26) (a) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Montgomery, J. A.; Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y. Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 03, revisions C.02 and D.02; Gaussian, Inc.: Wallingford, CT, 2004. (b) Zhao, Y.; Truhlar, D. G. The M06 Suite of Density Functionals for Main Group Thermochemistry, Thermochemical Kinetics, Noncovalent Interactions, Excited States, and Transition Elements: Two New Functionals and Systematic Testing of Four M06-Class Functionals and 12 Other Functionals.Theor. Chem. Acc. 2008, 2008 120, 215–241. (c) Hariharan, P.C.; Pople, J. A. The Influence of Polarization Functions on Molecular Orbital Hydrogenation Energies. Theoret. Chimica Acta. 1973, 1973 28, 213–222. d) Scalmani, G.; Frisch, M. J. Continuous Surface Charge Polarizable Continuum Models of Solvation. I. General Formalism.J. Chem. Phys. 2010, 2010 132, 114110. (27) (a) Ori, M.; Toda, N.; Takami, K.; Tago, K.; Kogen, H. Stereospecific Construction of Contiguous Quaternary and Tertiary Stereocenters by Rearrangement from Indoline-2-methanol to 2,2,3-Trisubstituted Tetrahydroquinoline: Application to an Efficient Total Synthesis of Natural Virantmycin. Angew. Chem. Int. Ed. 2003 2003, 03 42, 2540–2543. (b) Ori, M.; Toda, N.; Takami, K.; Tago, K.; Kogen, H. Stereospecific Synthesis of 2,2,3-Trisubstituted Tetrahydroquinolines: Application to the Total Syntheses of Benzastatin E and Natural Virantmycin.Tetrahedron 2005, 2005 61, 2075–2104.


Page 16 of 16

Synthesis of 1,2-Dihydroquinazolines via Rearrangement of

Recommend Documents