Pd-Catalyzed Regioselective Mono-Arylation: Quinazolinone as the Inherent Directing Group for C(sp2)-H Activation

Article abstract of DOI:10.1021/acs.joc.7b00948

The Pd-catalyzed quinazolinone-directed regioselective monoarylation of aromatic rings by C-H bond activation is developed. A broad substrate scope is demonstrated for both quinazolinone as well as diaryliodonium triflates. The use of a base was found to be crucial for this transformation, unlike for the known nitrogen-directed arylations. All of the novel quinazolinones of biological interest were synthesized by using the operationally simple Pd(II)-catalyzed arylation reaction.

Full text of DOI:10.1021/acs.joc.7b00948

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Article
Pd-Catalyzed Regioselective Mono-Arylation: Quinazolinone
as the Inherent Directing Group for C(sp2)-H Activation
Dnyaneshwar Nilkanth Garad, Amol B. Viveki, and Santosh B. Mhaske
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 19 May 2017
Downloaded from http://pubs.acs.org on May 19, 2017
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Pd-Catalyzed Regioselective Mono-Arylation: Quinazolinone as the Inherent
Directing Group for C(sp2)-H Activation
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Dnyaneshwar N. Garad, Amol B. Viveki, and Santosh B. Mhaske*
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Division of Organic Chemistry, CSIR-National Chemical Laboratory, Pune 411 008, India
ABSTRACT: The Pd-catalyzed quinazolinone-directed regioselective mono-arylation of
aromatic rings by C-H bond activation is developed. A broad substrate scope is demonstrated for
both quinazolinone as well as diaryliodonium triflates. Use of base was found to be crucial for
this transformation, unlike the known nitrogen-directed arylations. All the novel quinazolinones
of biological interest were synthesised by using operationally simple Pd(II)-catalyzed arylation
reaction.
INTRODUCTION
Over 70% of the top branded drugs contain at least one heterocyclic nucleus as a part of its
overall skeleton. In particular, many synthetic drugs, bioactive natural products, and
agrochemicals encompassing nitrogen-heterocyclic scaffolds are most common.1 Quinazolinones
are one of the important nitrogen-containing heterocyclic motifs found in more than 200 natural
products as well as in several drugs (Figure 1).1b,2 The quinazolinone derivatives possess wide
range of pharmacological activities such as antimalarial, anticancer, antimicrobial, anti-diabetic,
anti-inflammatory, antihypertensive, anticonvulsant, diuretic etc.1-3 The synthesis of various
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natural, and synthetic derivatives of quinazolinones has acquired immense attention by the
scientific community because of their wide range of biological properties.1-3
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The application of C-H bond functionalization to form new carbon-carbon (C-C) and C-
heteroatom (C-X) bonds in the synthesis of structurally complex natural or unnatural compounds
has emerged as a powerful tool, and it is an area of contemporary interest.4 It provides direct
access and delivers more atom economical paths in the synthesis of complex structures as
compared to the traditional organic synthesis. Until now several C-H activation reactions in the
organic compounds have been developed with or without directing groups.4 The metal-catalyzed
inter- or intramolecular aromatic C-H arylation is one of the widely used key-step in the total
synthesis of several natural products,4h and the late-stage derivatization of bioactive molecules.4g
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Figure 1. Selected quinazolinone drugs, and natural products.1,2
Due to the extensive occurrence of quinazolinone nucleus in bioactive organic compounds, we
envisioned that the quinazolinone core could be exploited as the inherent directing group for the
metal-catalyzed regioselective arylation, which would afford novel quinazolinones for structure-
activity-relationship (SAR) studies. In this context, the literature survey revealed that, although
there are several classical methods available for the synthesis of novel quinazolinone
derivatives,2,5 but there are only a few reports in the literature where quinazolinone compounds
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itself were functionalized by metal catalysis. Pd-catalyzed oxygenations,6 and oxidative C-H
aminations7 was reported by Reddy, and Wu et al. respectively. Besson, and co-workers reported
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regioselective
arylation
of
(2H)-quinazolin-4-ones.8
Pd-catalyzed
syntheses
of
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phenanthridine/benzoxazine fused quinazolinones were reported by using three different
approaches; intramolecular C-H activation with bromoarenes,9 intramolecular oxidative C-H
amination,10 and cascade C–H/N–H arylation.11 Few other metal catalysts were utilized in the
quinazolinone/quinazoline functionalization such as rhodium-catalyzed regioselective direct C-H
amidation,12 copper-catalyzed cascade amination,13 and Ru/Rh-catalyzed annulation reactions.14
Nevertheless, to the best of our knowledge, quinazolinone-directed intermolecular arylation of
quinazolinone compounds is not known until now.
RESULTS AND DISCUSSION
Herein, we report a protocol for the arylation of various quinazolinones. The optimization of the
protocol was carried out by screening various reaction parameters. Initial attempts on N-H free
quinazolinone 1 as the substrate with various halo-benzenes 2 failed to produce coupling product
3. Hence, we planned to study the protocol on various N-substituted quinazolinones. The N-
methyl substituted quinazolinone substrate 1a on treatment with halo-benzenes 2, Pd-catalyst,
and other additives did not furnish the expected product 3a under various reaction conditions
(Table 1). These observations suggest that more activated arylation reagent was necessary for
this transformation. Diaryliodonium salts are well-known compounds as an arylation reagent due
to their easy accessibility, and high reactivity.15 Because of their highly electron-deficient nature,
and good leaving group aptitude, they serve as versatile arylation agents with various metal
catalysts.16 Hence, we changed the phenyl source from halo-benzenes to diphenyliodonium
triflate 2a, and to our delight expected product 3a was formed in 35% yield (entry 2).
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Table 1. Optimization Studies
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entrya, b
yield (%)c
N.R.
2/2a-c (equiv)
additive (equiv)
solvent
1
2
3
2 (2)
2a (1)
2a (1)
AgOAc (2)
K2CO3 (1)
K2CO3 (1)
AcOH
AcOH
toulene
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N.R.
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2a (1)
2b (1)
K2CO3 (1)
K2CO3 (1)
1,4-dioxane
N.R.
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AcOH
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2c (1)
K2CO3 (1)
AcOH
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2a (1)
2a (2)
-
AcOH
AcOH
N.R.
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Na2CO3 (2)
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2a (3)
Na2CO3 (2)
AcOH
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2a (3)
2a (3)
NaOAc (2)
Na2CO3 (2)
AcOH
PivOH
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trace
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2a (3)
Na2CO3 (2)
AcOH:PivOH
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aSelected entries, bReaction conditions: 1a(0.2 mmol), AcOH (1 mL) in sealed tube for 36 h. cIsolated yield. N.R. = No reaction.
The variation in solvents did not show the formation of expected product (entries 3, 4). Also the
use of unsymmetrical iodonium salt 2b or iodonium salt 2c having different counterion gave
lower yields (entries 5, 6). We did not observe the expected product 3a in the absence of base
(entry 7), and the substrate 1a was recovered unchanged, which suggests that the use of base is
crucial for this reaction. This observation is in contrast to the reported Pd-catalyzed nitrogen-
directed arylation by C-H activation using diaryliodonium salts.4j,k When two equivalents of the
iodonium salt 2a was used in combination with Na2CO3, we observed an improvement in the
yield to 55% (entry 8). The highest possible yield of the product 3a was 71% wherein three
equivalent of salt 2a was used (entry 9). Further, variation in the optimized conditions like a
change in the base NaOAc (entry 10), solvent PivOH (entry 11), solvent combinations of
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AcOH:PivOH (entry 12), and temperature, etc. resulted in either low or trace amount of product
formation.
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With the optimized conditions in hand, we next turned our attention to develop a general
scope of the protocol. We planned to study the effect of substituent variation in the
quinazolinone core on the arylation reaction (Table 2).
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Table 2. Pd-Catalyzed Arylation of Various Quinazolinonesa,b
aReaction conditions: 1a-r (0.2 mmol), 2a (0.6 mmol), Pd(OAc)2 (10 mol%), Na2CO3 (0.4 mmol), AcOH (1 mL), 30-36 h, 90-
120 oC. bIsolated yield. cTrace product formation was confirmed by TLC, and HRMS.
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Initially, the effect of N-substitution was studied. N-Primary alkyl substituted quinazolinones
furnished the expected products 3a-c with moderate to good yields. We observed that with the
increase in the chain length the yield of the respective product decreases. The quinazolinone
substrate with N-benzyl substituent resulted in the moderate yield of 3d. The N-Phenyl
substituted quinazolinone provided only trace amount of product 3e. The reason behind this
observation might be the steric hindrance caused by the N-phenyl ring, which enforces the other
phenyl ring out of the plane, thus inhibiting the formation of palladacycle. The quinazolinone
substrate with N-methoxy substituent furnished 3f in good yield. The N-methyl substituted
quinazolinone provided better yield than the substrates with other N-substituents. Keeping the N-
methyl substitution constant, the further scope of the arylation reaction with varyingly
substituted quinazolinone core was explored. 5-Methyl substituted quinazolinone gave the
corresponding arylated product 3g in good yield, however, 6-chloro, and 6-nitro substituted
quinazolinones resulted in low, and trace yield of products 3h, and 3i respectively. Most
probably, the electron withdrawing substituents weakens the coordinating ability of these
substrates with the metal catalyst, which resulted in lower yields. Electron rich substituents
provided the arylated products 3j and 3k in very good yields. The heterocyclic substrate could
only afford trace amount of product 3l due to electron withdrawing effect of the pyridine ring.
Furthermore, we began to explore the substrate scope of the aromatic ring attached to the
quinazolinone core. The quinazolinone substrate with alkyl substituted aromatic ring resulted in
the decent yield of product 3m, however, as anticipated chloro, and other electron withdrawing
substituents resulted in moderate to a low yield of products 3n-p. Electron rich substituent
enhanced the C-H activation process, and the product 3q was obtained in excellent yield.
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Pleasingly, the heterocyclic indole substrate could be arylated at the 2-position of indole to
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afford the product 3r.
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Table 3. Pd-Catalyzed Arylation with Various Diaryliodonium Triflatesa,b
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aReaction conditions: 1q (0.2 mmol), 2b-i (0.6 mmol), Pd(OAc)2 (10 mol%), Na2CO3 (0.4 mmol), AcOH (1 mL), 30-36 h, 90-95
oC. bIsolated yield.
We also investigated the application of various diaryliodonium triflates in the developed
arylation protocol (Table 3). The substrate 1q was chosen for this purpose. It is well known that
the sterically less hindered aryl group of diaryliodonum triflate undergoes metal-catalyzed
coupling,16d hence we kept sterically hindered mesitylene as one of the substituent in the
arylation reagent, and varied other aryl substituents. Various substituents on the arylation reagent
were tolerated under the developed protocol. The arylated products such as unsubstituted 3q and
methyl substituted 3s could be obtained in very good yields. The para-fluoro compound 3t was
obtained in moderate yield. The arylation reagents with electron withdrawing groups underwent
smooth reactions under the developed protocol. The trifluoromethyl and ester groups at meta-
position on arylation reagent were well tolerated, and expected products 3u, and 3v have been
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synthesized in decent yields respectively. Nitro groups at meta- and para-positions of arylating
reagents provided good yields of products 3w, and 3x respectively. Overall, it was observed that
electron withdrawing groups on arylation reagents facilitates the reaction. It can be reasoned that
the palladium insertion takes place promptly on more electron deficient coupling partner. As
evident from the substrate scope study (Tables 2, and 3), the developed protocol is very general,
and it will be suitable for generation of a library of compounds.
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A plausible mechanism for the developed arylation protocol is depicted in Figure 2, based
on the literature precedence.4j,7,17
Figure 2. Proposed mechanism.
We believe that in the first step Pd(II) coordinates with the imine nitrogen of quinazolinone 1a,
and activates the proximal proton to form a five membered palladacycle A. Diphenyliodonium
triflate 2a oxidatively adds to the palladacycle A [Pd(II)] to form the palladacycle B [Pd(IV)].
Subsequently, base promoted reductive elimination affords product 3a, and Pd(II) regenerates for
the next catalytic cycles.
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CONCLUSION
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In summary, quinazolinone scaffold has been demonstrated as the inherent directing group in Pd-
catalyzed intermolecular regioselective mono-arylation reaction. Diaryliodonium triflates have
been used as arylation reagents in the C-H activation process, which provided the wide range of
new quinazolinones. This novel protocol could be used for late-stage derivatisation of bioactive
quinazolinones, and natural products for SAR studies. Screening the anticancer, and antimalarial
properties of all the synthesized new quinazolinone compounds, and the work towards the
development of quinazolinone as a directing group for other C-H activation processes is
underway in our laboratory.
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EXPERIMENTAL SECTION
General Information: All reagents and solvents were used as received from commercial sources
unless and otherwise noted. All experiments were carried out under argon atmosphere in the
sealed tube. Pre-coated plates (silica gel 60 PF254, 0.25 mm or 0.5 mm) were utilized for Thin
Layer Chromatography (TLC). Column chromatographic purifications were carried out on flash
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silica-gel (240-400 mesh) using petroleum ether and ethyl acetate as eluents. The H, C NMR
spectra were recorded on 200/400/500 MHz, and 50/100/125 MHz NMR spectrometer
respectively in CDCl3. Chemical shifts were reported as δ values from standard peaks. Melting
points were recorded on Buchi instrument. Mass spectra were taken on LC-MS (ESI) mass
spectrometer. High-resolution mass spectrometry (HRMS) was performed on a TOF/Q-TOF
mass spectrometer. All diaryliodonium triflates15c-d,18 and quinazolinone starting materials19,20
were prepared according to well-known literature procedures.
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Experimental Procedures for the Synthesis of Starting Materials:
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Method A: The literature known procedure was followed.19 N-Substituted anthranilamides (1.0
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mmol; 1.0 equiv.), and aromatic aldehydes (1.2 mmol; 1.2 equiv.) were dissolved in DMSO (5
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mL). Then, the reaction mixture was stirred at 120 C in an open flask, and the progress was
monitored by TLC. After complete consumption (48 h) of the starting materials, the reaction
mixture was poured onto water and extracted with DCM. The organic layer was combined, dried
over anhydrous sodium sulfate, and concentrated in vacuo. The crude mixture was purified by
silica gel column chromatography using Pet. ether / EtOAc (5:1) as an eluent to afford 2,3-
disubstituted-4(3H)-quinazolinones 1a-r.
Method B: The literature known procedure was followed.20 To the solution of N-substituted
anthranilamides 4 (1 mmol) and p-TsOH (0.05 mmol) in THF (10 mL) was added aldehyde 5
(1.1 mmol) and the reaction mixture was then stirred at room temperature (RT) for 10 min.,
followed by portion wise addition of PIDA (1.5 mmol) over 5 min. After stirring for 1 h, the
reaction mixture was diluted with EtOAc (20 mL), quenched with saturated aqueous NaHCO3
solution (20 mL), and then extracted with EtOAc (3 × 20 mL). The combined organic layer was
washed with brine (3 × 30 mL), dried over sodium sulfate and concentrated in vacuo. The crude
mixture was purified by silica gel column chromatography using Pet. ether / EtOAc (5:1) as an
eluent to afford 2,3-disubstituted-4(3H)-quinazolinones 1a-r.
3-methyl-2-phenylquinazolin-4(3H)-one (1a).19 Following the Method A procedure, 1a was
obtained as white solid (178 mg; 75% yield). 1H NMR (200 MHz, CDCl3) δ (ppm) 8.35 (dt, J =
7.9, 1.1 Hz, 1H), 7.80-7.73 (m, 2H), 7.63-7.43 (m, 6H), 3.51 (s, 3H).
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3-ethyl-2-phenylquinazolin-4(3H)-one (1b).21 Following the Method A procedure, 1b was
obtained as white solid (167 mg; 67% yield). 1H NMR (200 MHz, CDCl3) δ (ppm) 8.35 (dt, J =
7.9, 1.0 Hz, 1H), 7.80-7.72 (m, 2H), 7.59-7.47 (m, 6H), 4.05 (q, J = 7.1 Hz, 2H), 1.23 (t, J = 7.1
Hz, 3H).
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3-butyl-2-phenylquinazolin-4(3H)-one (1c).5b Following the Method A procedure 1c was
obtained as white solid (122 mg; 44% yield). 1H NMR (200 MHz, CDCl3) δ (ppm) 8.34 (m, 1H),
7.79-7.70 (m, 2H), 7.56-7.46 (m, 6H), 4.05-3.92 (m, 2H), 1.65-1.50 (m, 2H), 1.28-1.08 (m, 2H),
0.78 (t, J = 7.1 Hz, 3H).
3-benzyl-2-phenylquinazolin-4(3H)-one (1d).19 Following the Method A procedure, 1d was
obtained as white solid (119 mg; 38% yield). 1H NMR (200 MHz, CDCl3) δ (ppm) 8.43-8.34 (m,
1H), 7.83-7.73 (m, 2H), 7.59-7.50 (m, 1H), 7.50-7.31 (m, 5H), 7.26-7.15 (m, 3H), 6.99-6.87 (m,
2H), 5.29 (s, 2H).
2,3-diphenylquinazolin-4(3H)-one (1e).19 Following the Method A procedure 1e was obtained as
white solid (203 mg; 68% yield). 1H NMR (200 MHz, CDCl3) δ (ppm) 8.37 (dt, J = 7.9, 1.0 Hz,
1H), 7.87-7.80 (m, 2H), 7.60-7.50 (m, 1H), 7.39-7.27 (m, 5H), 7.26-7.13 (m, 5H).
3-methoxy-2-phenylquinazolin-4(3H)-one (1f).20 Following the Method B procedure, 1f was
obtained as white solid (163 mg; 65% yield). 1H NMR (200 MHz, CDCl3) δ (ppm) 8.36 (dt, J =
7.9, 1 Hz, 1H), 7.96-7.86 (m, 2H), 7.82-7.76 (m, 2H), 7.61-7.46 (m, 4H), 3.78 (s, 3H).
3,5-dimethyl-2-phenylquinazolin-4(3H)-one (1g). Following the Method A procedure, 1g was
obtained as white solid (113 mg; 45% yield). Rf: 0.4 (1:4 EtOAc: Pet. ether); mp 105-107 oC; 1H
NMR (400 MHz, CDCl3) δ (ppm) 7.63-7.48 (m, 7H), 7.30-7.22 (m, 1H), 3.46 (s, 3H), 2.94 (s,
3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 163.2, 155.8, 148.9, 140.9, 135.5, 133.4, 129.9,
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129.5, 128.8, 127.9, 125.7, 119.1, 34.1, 23.1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C16H15N2O, 251.1179; found, 251.1181.
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6-chloro-3-methyl-2-phenylquinazolin-4(3H)-one (1h). Following the Method B procedure, 1h
was obtained as white solid (192 mg; 67% yield). Rf: 0.35 (1:4 EtOAc: Pet. ether); mp 126-128
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oC; H NMR (400 MHz, CDCl3) δ (ppm) 8.30 (s, 1H), 7.78-7.64 (m, 2H), 7.62-7.45 (m, 5H),
3.51 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 161.7, 156.4, 145.8, 135.1, 134.7, 132.7,
130.2, 129.2, 128.9, 127.9, 126.0, 121.5, 34.4; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C15H12N2OCl, 271.0633; found, 271.0636.
3-methyl-6-nitro-2-phenylquinazolin-4(3H)-one (1i).22 Following the Method A procedure, 1i
was obtained as yellow solid (90 mg; 32% yield). 1H NMR (200 MHz, CDCl3) δ (ppm) 9.21 (d, J
= 2.5 Hz, 1H), 8.55 (dd, J = 9.0, 2.5 Hz, 1H), 7.85 (d, J = 9.0 Hz, 1H), 7.64-7.57 (m, 5H), 3.57
(s, 3H).
6-methoxy-3-methyl-2-phenylquinazolin-4(3H)-one (1j).23 Following the Method A procedure,
1
1j was obtained as white solid (102 mg; 38% yield). H NMR (200 MHz, CDCl3) δ (ppm) 7.78-
7.65 (m, 2H), 7.63-7.48 (m, 5H), 7.37 (dd, J = 9.0, 3 Hz, 1H), 3.95 (s, 3H), 3.52 (s, 3H).
7-methoxy-3-methyl-2-phenylquinazolin-4(3H)-one (1k).23 Following the Method A procedure,
1
1k was obtained as white solid (120 mg; 45% yield). H NMR (200 MHz, CDCl3) δ (ppm) 8.24
(d, J = 8.8 Hz, 1H), 7.61-7.48 (m, 5H), 7.14 (d, J = 2.4 Hz, 1H), 7.09 (dd, J = 8.8, 2.4 Hz, 1H),
3.91 (s, 3H), 3.49 (s, 3H).
3-methyl-2-phenylpyrido[2,3-d]pyrimidin-4(3H)-one (1l).24 Following the Method A procedure
1
1l was obtained as white solid (87 mg; 37% yield). H NMR (200 MHz, CDCl3) δ (ppm) 9.01
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(dd, J = 4.6, 2 Hz, 1H), 8.66 (dd, J = 7.9, 2 Hz, 1H), 7.71-7.60 (m, 2H), 7.58-7.41 (m, 4H), 3.56
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(s, 3H).
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3-methyl-2-(p-tolyl)quinazolin-4(3H)-one (1m).25 Following the Method A procedure, 1m was
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obtained as white solid (160 mg; 64% yield). H NMR (200 MHz, CDCl3) δ (ppm) 8.34 (d, J =
7.8 Hz, 1H), 7.70-7.69 (m, 2H), 7.56-7.41 (m, 3H), 7.33 (d, J = 8 Hz, 2H), 3.52 (s, 3H), 2.45 (s,
3H).
2-(4-chlorophenyl)-3-methylquinazolin-4(3H)-one (1n).21 Following the Method A procedure,
1
1n was obtained as white solid (152 mg; 56% yield). H NMR (200 MHz, CDCl3) δ (ppm) 8.32
(d, J = 7.5 Hz, 1H), 7.83-7.67 (m, 2H), 7.60-7.45 (m, 5H), 3.50 (s, 3H).
3-methyl-2-(4-(trifluoromethyl)phenyl)quinazolin-4(3H)-one (1o). Following the Method B
procedure, 1o was obtained as white solid (131 mg; 43% yield). Rf: 0.35 (1:4 EtOAc: Pet. ether);
o
1
mp 119-121 C; H NMR (400 MHz, CDCl3) δ (ppm) 8.35 (d, J = 7.9 Hz, 1H), 7.88-7.69 (m,
13
6H), 7.54 (t, J = 7.3 Hz, 1H), 3.50 (s, 3H); C NMR (100 MHz, CDCl3) δ (ppm) 162.4, 154.7,
147, 138.7, 134.5, 132.1 (q, J = 33.1 Hz), 128.6, 127.5, 127.4, 126.8, 125.9 (q, J = 3.8 Hz), 123.6
(q, J = 272 Hz), 120.6, 34.1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C16H12N2OF3,
305.0896; found, 305.0893.
3-methyl-2-(4-nitrophenyl)quinazolin-4(3H)-one (1p).25 Following the Method B procedure, 1p
was obtained as yellow solid (129 mg; 46% yield). 1H NMR (200 MHz, CDCl3) δ (ppm) 8.43 (d,
J = 8.8 Hz, 2H), 8.37 (d, J = 8.7 Hz, 1H), 7.87-7.74 (m, 4H), 7.63-7.51 (m, 1H), 3.51 (s, 3H).
2-(4-methoxyphenyl)-3-methylquinazolin-4(3H)-one (1q).21 Following the Method A procedure,
1
1q was obtained as white solid (181 mg; 68% yield). H NMR (200 MHz, CDCl3) δ (ppm) 8.32
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(d, J = 7.7 Hz, 1H), 7.78-7.68 (m, 2H), 7.59-7.44 (m, 3H), 7.08-6.98 (m, 2H), 3.88 (s, 3H), 3.54
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(s, 3H).
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3-methyl-2-(1-methyl-1H-indol-3-yl)quinazolin-4(3H)-one (1r). Following the Method A
procedure, 1r was obtained as white solid (130 mg; 45% yield). Rf: 0.4 (1:1 EtOAc: Pet. ether);
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mp 194-196 C; H NMR (400 MHz, CDCl3) δ (ppm) 8.35 (d, J = 7.3 Hz, 1H), 7.80-7.70 (m,
3H), 7.55 (s, 1H), 7.51-7.45 (m, 1H), 7.42 (d, J = 7.9 Hz, 1H), 7.34 (t, J = 7.9 Hz, 1H), 7.27 (t, J
13
= 7.9 Hz, 1H), 3.91 (s, 3H), 3.72 (s, 3H); C NMR (100 MHz, CDCl3) δ (ppm) 163.3, 152.1,
147.9, 136.8, 134.1, 130.6, 127.2, 126.6, 126.4, 126.2, 122.9, 121.2, 120.7, 120.1, 110.5, 109.9,
34.1, 33.2; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C18H16N3O, 290.1288; found, 290.1293.
General Experimental Procedure for Arylations by C-H Activation:
A sealed tube was charged with quinazolinone 1a-r (0.2 mmol), diaryl iodonium triflate 2a-i (0.6
mmol), sodium carbonate (42 mg; 0.4 mmol) and Pd(OAc)2 (4.5 mg; 10 mol%). To the above
mixture AcOH (1 ml; 0.2M) was added and flushed twice with argon gas. The tube was packed
o
o
with screw cap and placed in preheated oil bath at 90 C-120 C. The progress of the reaction
was monitored by TLC. The reaction mixture was cooled to RT after 30-36 h, diluted with ethyl
acetate and evaporated under vacuo to dryness. After aqueous workup the residue was purified
by column chromatography to afford pure quinazolinone 3a-x.
2-([1,1'-biphenyl]-2-yl)-3-methylquinazolin-4(3H)-one (3a). Following the general experimental
procedure, 3a was obtained as a colorless solid (44 mg; 71% yield); Reaction Time: 36 h at 95
oC. Rf: 0.4 (1:4 EtOAc:Pet. ether); mp 125-127 oC; 1H NMR (400 MHz, CDCl3) δ (ppm) 8.27 (d,
J = 7.9 Hz, 1H), 7.84-7.76 (m, 2H), 7.67-7.57 (m, 2H), 7.56-7.47 (m, 3H), 7.37-7.30 (m, 2H),
7.27-7.22 (m, 3H), 3.01 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 162.1, 156.4, 147.1,
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140.2, 139.4, 134.2, 134.1, 130.4, 130.2, 129.2, 128.7, 128.5, 128.1, 128, 127.5, 126.9, 126.7,
120.4, 32.6; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C21H17N2O, 313.1335; found, 313.1337.
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2-([1,1'-biphenyl]-2-yl)-3-ethylquinazolin-4(3H)-one (3b). Following the general experimental
procedure, 3b was obtained as a colorless solid (36 mg, 55% yield); Reaction time: 36 h at 100
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o
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oC; Rf: 0.4 (1:4 EtOAc:Pet. ether); mp 137-139 C; H NMR (400 MHz, CDCl3) δ (ppm) 8.27
(d, J = 7.93, 1H), 7.88-7.75 (m, 2H), 7.65-7.55 (m, 2H), 7.54-7.49 (m, 3H), 7.40-7.32 (m, 2H),
7.26-7.16 (m, 3H), 4.0-3.90 (m, 1H), 3.37-3.27 (m, 1H), 0.96 (t, J = 7.0 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ (ppm) 161.5, 156.1, 146.6, 140.0, 139.3, 134.3, 133.7, 130.4, 130.1, 129.2,
128.7, 128.6, 127.9, 127.8, 127.2, 127, 126.7, 120.8, 40.5, 13.5; HRMS (ESI-TOF) m/z: [M +
H]+ Calcd for C22H19N2O, 327.1492; found, 327.1495.
2-([1,1'-biphenyl]-2-yl)-3-butylquinazolin-4(3H)-one (3c). Following the general experimental
procedure, 3c was obtained as a colorless solid (37 mg, 53% yield); Reaction time: 30 h at 90 oC;
Rf: 0.4 (1:4 EtOAc:Pet. ether); mp 108-110 oC; 1H NMR (400 MHz, CDCl3) δ (ppm) 8.26 (d, J =
7.94, 1H), 7.83-7.76 (m, 2H), 7.63-7.56 (m, 2H), 7.55-7.48 (m, 3H), 7.37-7.32 (m, 2H), 7.26-
7.21 (m, 3H), 3.87-3.77 (m, 1H), 3.27-3.17 (m, 1H), 1.45-1.32(m, 2H), 1.11-1.0(m, 2H), 0.66 (t,
J = 7.32, 3H) ; 13C NMR (100 MHz, CDCl3) δ (ppm) 161.8, 156.2, 147, 140, 139.4, 134.2, 134.1,
130.3, 130, 129.5, 128.6, 127.9, 127.8, 127.4, 126.8, 126.7, 120.9, 45, 30.1, 19.8, 13.3; HRMS
(ESI-TOF) m/z: [M + H]+ Calcd for C24H23N2O, 355.1805; found, 355.1806.
2-([1,1'-biphenyl]-2-yl)-3-benzylquinazolin-4(3H)-one (3d). Following the general experimental
procedure, 3d was obtained as a colorless solid (34 mg, 44% yield); Reaction time: 36 h at 120
oC; Rf: 0.4 (1:4 EtOAc:Pet. ether); mp 84-85 oC; 1H NMR (400 MHz, CDCl3) δ (ppm) 8.29 (d, J
= 7.94, 1H), 7.82 (d, J = 6.72 Hz, 2H), 7.59-7.50 (m, 3H), 7.40-7.28 (m, 5H), 7.27-7.20 (m, 2H),
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7.16-7.09 (m, 3H), 6.77 (d, J = 7.32, 2H), 5.27 (d, J = 15 Hz, 1H), 4.30 (d, J = 15 Hz, 1H),13C
NMR (100 MHz, CDCl3) δ (ppm) 162, 156.3, 146.8, 139.9, 139.4, 136.2, 134.5, 133.7, 130.4,
130, 129.9, 128.8, 128.7, 128.3, 128, 127.7, 127., 127.3, 127.1, 120.8, 47.7; HRMS (ESI-TOF)
m/z: [M + H]+ Calcd for C27H21N2O, 389.1648; found, 389.1648.
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2-([1,1'-biphenyl]-2-yl)-3-phenylquinazolin-4(3H)-one (3e). Following the general experimental
procedure, 3e was formed in trace amount by TLC analysis and also confirmed by LC-HRMS;
o
Reaction time: 36 h at 120 C; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C26H19N2O,
375.1492; found, 375.1500.
2-([1,1'-biphenyl]-2-yl)-3-methoxyquinazolin-4(3H)-one
(3f).
Following
the
general
experimental procedure, 3f was obtained as a colorless solid (45 mg; 69% yield); Reaction Time:
o
o
36 h at 90 C. Rf: 0.4 (1:3 EtOAc:Pet. ether); mp 101-103 C; 1H NMR (400 MHz, CDCl3) δ
(ppm) 8.28 (d, J = 7.9 Hz, 1H), 7.82-7.76 (m, 2H), 7.65 (d, J = 7.3 Hz, 1H), 7.61 (d, J = 7.3 Hz,
1H), 7.55-7.48 (m, 3H), 7.37-7.31 (m, 2H), 7.26-7.20 (m, 3H), 3.62 (s, 3H); 13C NMR (100
MHz, CDCl3) δ (ppm) 157.6, 156.5, 146.3, 141.6, 140.1, 134.4, 131.4, 130.5, 130, 129.1, 128.5,
128.4, 127.9, 127.5, 127.2, 127, 126.7, 122.7, 64; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C21H17N2O2, 329.1285; found, 329.1286.
2-([1,1'-biphenyl]-2-yl)-3,5-dimethylquinazolin-4(3H)-one (3g). Following the general
experimental procedure, 3g was obtained as a colorless solid (41 mg; 63% yield); Reaction
Time: 36 h at 95 oC. Rf: 0.4 (1:4 EtOAc:Pet. ether); mp 124-126 oC; 1H NMR (400 MHz, CDCl3)
δ (ppm) 7.66-7.49 (m, 6H), 7.39-7.32 (m, 2H), 7.29-7.23 (m, 4H), 2.95 (s, 3H), 2.87 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ (ppm) 162.7, 156.1, 148.8, 140.9, 140.2, 139.6, 134.2, 133.3, 130.3,
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130.2, 129.5, 129.2, 128.7, 128.6, 128.1, 127.9, 125.7, 119, 32.5, 23.1; HRMS (ESI-TOF) m/z:
[M + H]+ Calcd for C22H19N2O, 327.1492; found, 327.1494.
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2-([1,1'-biphenyl]-2-yl)-6-chloro-3-methylquinazolin-4(3H)-one (3h). Following general
experimental procedure 3h was obtained as a colorless solid (17 mg; 25% yield); Reaction Time:
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36 h at 120 C. Rf: 0.35 (1:3 EtOAc:Pet. ether); mp 129-131 C; 1H NMR (400 MHz, CDCl3) δ
(ppm) 8.22 (s, 1H), 7.76-7.69 (m, 2H), 7.66-7.60 (m, 1H), 7.59-7.51 (m, 3H), 7.34-7.29 (m, 2H),
7.27-7.21 (m, 3H), 3.00 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 161.1, 156.7, 145.6,
140.3, 139.3, 134.8, 133.8, 132.7, 130.6, 130.2, 129.2, 129.1, 128.8, 128.5, 128.1, 127.06, 126,
121.4, 32.7; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C21H16N2OCl, 347.0946; found,
347.0951.
2-([1,1'-biphenyl]-2-yl)-3-methyl-6-nitroquinazolin-4(3H)-one (3i). Following the general
experimental procedure, 3i was formed in trace amount by TLC analysis and also confirmed by
LC-HRMS; Reaction time: 36 h at 120 C; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
o
C21H16N3O3, 358.1186; found, 358.1188.
2-([1,1'-biphenyl]-2-yl)-6-methoxy-3-methylquinazolin-4(3H)-one (3j). Following the general
experimental procedure, 3j was obtained as a colorless solid (52 mg; 76% yield); Reaction Time:
36 h at 95 C. Rf: 0.35 (1:2 EtOAc:Pet. ether); mp 177-179 C; 1H NMR (400 MHz, CDCl3) δ
o
o
(ppm) 7.74 (d, J = 8.5 Hz, 1H), 7.65-7.48 (m, 5H), 7.39 (dd, J = 8.5, 2.4 Hz, 1H), 7.35-7.29 (m,
13
2H), 7.28-7.20 (m, 3H), 3.93 (s, 3H), 3.01 (s, 3H); C NMR (100 MHz, CDCl3) δ (ppm) 162,
158.5, 154.2, 141.8, 140.3, 139.5, 134.1, 130.4, 130.1, 129.3, 129.1, 128.7, 128.5, 128.1, 127.9,
124.7, 121.2, 105.9, 55.8, 32.6; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H19N2O2,
343.1441; found, 343.1441.
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2-([1,1'-biphenyl]-2-yl)-7-methoxy-3-methylquinazolin-4(3H)-one (3k). Following general
experimental procedure 3k was obtained as a colorless solid (48 mg; 70% yield); Reaction Time:
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o
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36 h at 95 C. Rf: 0.35 (1:2 EtOAc:Pet. ether); mp 197-199 C; 1H NMR (400 MHz, CDCl3) δ
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(ppm) 8.15 (d, J = 8.6 Hz, 1H), 7.65-7.48 (m, 4H), 7.37-7.30 (m, 2H), 7.28-7.22 (m, 3H), 7.19
13
(d, J = 1.8 Hz, 1H), 7.08 (dd, J = 8.5, 1.8 Hz, 1H), 3.94 (s, 3H), 2.98 (s, 3H); C NMR (100
MHz, CDCl3) δ (ppm) 164.5, 161.7, 157.2, 149.3, 140.1, 139.4, 134.2, 130.4, 130.1, 129.1,
128.7, 128.5, 128.2, 128.03, 128, 117.2, 114, 107.8, 55.6, 32.4; HRMS (ESI-TOF) m/z: [M + H]+
Calcd for C22H19N2O2, 343.1441; found, 343.1432.
2-([1,1'-biphenyl]-2-yl)-3-methylpyrido[2,3-d]pyrimidin-4(3H)-one (3l). Following the general
experimental procedure, 3l was formed in trace amount by TLC analysis and also confirmed by
o
LC-HRMS; Reaction time: 36 h at 120 C; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C20H16N3O, 314.1288; found, 314.1286.
3-methyl-2-(5-methyl-[1,1'-biphenyl]-2-yl)quinazolin-4(3H)-one (3m). Following the general
experimental procedure, 3m was obtained as a colorless solid (48 mg; 74% yield); Reaction
Time: 36 h at 95 oC. Rf: 0.4 (1:4 EtOAc:Pet. ether); mp 151-153 oC; 1H NMR (400 MHz, CDCl3)
δ (ppm) 8.26 (d, J = 7.9 Hz, 1H), 7.82-7.74 (m, 2H), 7.55-7.44 (m, 2H), 7.38-7.29 (m, 4H), 7.26-
7.17 (m, 3H), 3.00 (s, 3H), 2.49 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 162.2, 156.6,
147.2, 140.5, 140.1, 139.6, 134.2, 131.4, 130.8, 129.1, 128.68, 128.66, 128.5, 127.8, 127.4,
126.8, 126.6, 120.4, 32.6, 21.4; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H19N2O,
327.1492; found, 327.1494.
2-(5-chloro-[1,1'-biphenyl]-2-yl)-3-methylquinazolin-4(3H)-one (3n). Following the general
experimental procedure, 3n was obtained as a colorless solid (30 mg, 43% yield); Reaction time:
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o
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30 h at 90 C; Rf: 0.5 (1:2 EtOAc:Pet. ether); mp 148-150 C; H NMR (400 MHz, CDCl3) δ
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(ppm) 8.26 (d, J = 7.9 Hz, 1H), 7.83-7.75 (m, 2H), 7.58-7.48 (m, 4H), 7.34-7.29 (m, 2H), 7.29-
7
8
9
13
7.21 (m, 3H), 2.99 (s, 3H); C NMR (100 MHz, CDCl3) δ (ppm) 162, 155.4, 147, 142, 138.2,
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136.4, 134.4, 132.6, 130.7, 130.1, 128.9, 128.5, 128.4, 128.1, 127.5, 127.1, 126.7, 120.5, 32.5;
HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C21H16N2OCl, 347.0946; found, 347.0941.
3-methyl-2-(5-(trifluoromethyl)-[1,1'-biphenyl]-2-yl)quinazolin-4(3H)-one (3o). Following the
general experimental procedure, 3o was obtained as a colorless solid (16 mg; 21% yield);
o
o
1
Reaction Time: 36 h at 120 C. Rf: 0.35 (1:2 EtOAc:Pet. ether); mp 140-142 C; H NMR (400
MHz, CDCl3) δ (ppm) 8.28 (d, J = 7.9 Hz, 1H), 7.85-7.70 (m, 5H), 7.54 (t, J = 7.3 Hz, 1H),
7.39-7.32 (m, 2H), 7.32-7.27 (m, 3H), 3.01 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 161.9,
155, 146.9, 141.2, 138, 137.3, 134.5, 132.6 (q, J = 33.1 Hz), 130, 129, 128.7, 128.4, 127.5,
127.3, 127.1 (q, J = 3.9 Hz), 126.8, 124.9 (q, J = 3.9 Hz), 123.6 (q, J = 272 Hz), 120.5, 32.6;
HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H16N2OF3, 381.1209; found, 381.1209.
3-methyl-2-(5-nitro-[1,1'-biphenyl]-2-yl)quinazolin-4(3H)-one (3p). Following the general
experimental procedure, 3p was obtained as a colorless solid (11 mg; 16% yield); Reaction
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Time: 36 h at 120 C. Rf: 0.3 (1:2 EtOAc:Pet. ether); mp 215-217 C; H NMR (400 MHz,
CDCl3) δ (ppm) 8.43 (s, 1H), 8.39 (d, J = 8.6 Hz, 1H), 8.28 (d, J = 7.9 Hz, 1H), 7.87-7.75 (m,
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3H), 7.56 (t, J = 7.3 Hz, 1H), 7.41-7.29 (m, 5H), 2.99 (s, 3H); C NMR (100 MHz, CDCl3) δ
(ppm) 161.7, 154.3, 148.9, 146.8, 142.1, 139.7, 137.2, 134.6, 130.8, 129.2, 128.4, 127.56,
127.55, 126.8, 125.1, 122.8, 120.5, 32.4; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C21H16N3O3, 358.1186; found, 358.1185.
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2-(5-methoxy-[1,1'-biphenyl]-2-yl)-3-methylquinazolin-4(3H)-one (3q). Following the general
experimental procedure, 3q was obtained as a colorless solid (59 mg, 86% yield); Reaction time:
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30 h at 90 C; Rf: 0.5 (1:1 EtOAc:Pet. ether); mp 192-194 C; H NMR (400 MHz, CDCl3) δ
(ppm) 8.25 (d, J = 7.94, 1H), 7.81-7.75 (m, 2H), 7.55-7.46 (m, 2H), 7.36-7.32 (m, 2H), 7.26-7.22
(m, 3H), 7.07-7.07 (m, 2H), 3.92 (s, 3H), 3.0 (s, 3H); ;13C NMR (100 MHz, CDCl3) δ (ppm)
162.3, 161, 156.5, 147.2, 141.9, 139.5, 134.2, 130.8, 128.7, 128.4, 128.1, 127.4, 126.9, 126.8,
126.6, 120.4, 115.5, 113.4, 55.6, 32.7; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H19N2O2,
343.1441; found, 343.1443.
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3-methyl-2-(1-methyl-2-phenyl-1H-indol-3-yl)quinazolin-4(3H)-one (3r). Following the general
experimental procedure, 3r was obtained as a colorless solid (33 mg; 45% yield); Reaction Time:
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36 h at 100 C. Rf: 0.5 (1:4 EtOAc:Pet. ether); mp 198-200 C; H NMR (400 MHz, CDCl3) δ
(ppm) 8.31 (d, J = 7.9 Hz, 1H), 7.79-7.72 (m, 2H), 7.64 (d, J = 7.9 Hz, 1H), 7.51-7.33 (m, 8H),
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7.28-7.23 (m, 1H), 3.80 (s, 3H), 3.20 (s, 3H); C NMR (100 MHz, CDCl3) δ (ppm) 163, 152.2,
147.8, 140, 137.5, 134, 130.6, 129.9, 129.02, 128.95, 127.5, 126.8, 126.6, 126.5, 123.1, 121.5,
120.4, 119.6, 110, 109.5, 32.9, 31.4; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C24H20N3O,
366.1601; found, 366.1606.
2-(5-methoxy-4'-methyl-[1,1'-biphenyl]-2-yl)-3-methylquinazolin-4(3H)-one (3s). Following the
general experimental procedure, 3s was obtained as a colorless solid (51 mg, 71% yield);
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Reaction time: 36 h at 95 C; Rf: 0.5 (1:1 EtOAc:Pet. ether); mp 130-132 C; H NMR (400
MHz, CDCl3) δ (ppm) 8.26 (d, J = 7.93, 1H), 7.84-7.76 (m, 2H), 7.54-7.44 (m, 2H), 7.22 (m, J =
7.32, 2H), 7.08-7.00 (m, 4H), 3.91 (s, 3H), 2.99 (s, 3H), 2.28 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ (ppm) 162.3, 160.9, 156.7, 147.3, 141.9, 138, 136.6, 134.2, 130.8, 129.5, 128.2, 127.4,
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126.8, 126.7, 126.6, 120.4, 115.4, 113.1, 55.5, 32.60 21.1; HRMS (ESI-TOF) m/z: [M + H]+
Calcd for C23H21N2O2, 357.1598; found, 357.1600.
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2-(4'-fluoro-5-methoxy-[1,1'-biphenyl]-2-yl)-3-methylquinazolin-4(3H)-one (3t). Following the
general experimental procedure, 3t was obtained as a colorless solid (32 mg, 44% yield);
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Reaction time: 36 h at 90 C; Rf: 0.5 (1:1 EtOAc:Pet. ether); mp 155-157 C; H NMR (500
MHz, CDCl3) δ (ppm) 8.26 (d, J = 7.62, 1H), 7.82-7.7.76 (m, 2H), 7.53-7.48 (m, 2H), 7.34-7.29
(m, 2H), 7.05 (dd, J = 2.7, 8.6 Hz, 1H), 7.01 (d, J = 2.7, 1H), 6.95 (t, J = 8.6 Hz 2H), 3.92 (s,
3H), 3.02 (s, 3H); 13C NMR (125 MHz, CDCl3) δ (ppm) 162.5 (d, J = 248 Hz), 162.2, 161,
156.2, 147.2, 140.8, 135.5 (d, J = 2.86 Hz), 134.3, 130.8, 130.1 (d, J = 7.63 Hz), 127.4, 126.9,
126.9, 126.7, 120.4, 115.8 (d, J = 21 Hz), 115.6, 113.4, 55.56, 32.7; HRMS (ESI-TOF) m/z: [M
+ H]+ Calcd for C22H18N2O2F, 361.1347; found, 361.1347.
2-(5-methoxy-3'-(trifluoromethyl)-[1,1'-biphenyl]-2-yl)-3-methylquinazolin-4(3H)-one
(3u).
Following the general experimental procedure, 3u was obtained as a colorless solid (60 mg; 73%
o
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yield); Reaction Time: 36 h at 95 C. Rf: 0.3 (1:2 EtOAc:Pet. ether); mp 142-144 C; H NMR
(400 MHz, CDCl3) δ (ppm) 8.25 (d, J = 7.3 Hz, 1H), 7.83-7.72 (m, 2H), 7.68 (s, 1H), 7.57-7.45
(m, 4H), 7.35 (t, J = 7.3 Hz, 1H), 7.13-7.07 (m, 1H), 7.05 (d, J = 1.8 Hz, 1H), 3.94 (s, 3H), 3.02
13
(s, 3H); C NMR (100 MHz, CDCl3) δ (ppm) 162.2, 161, 155.6, 146.9, 140.21, 140.17, 134.3,
131.6, 131.1 (q, J = 32.4 Hz), 130.7, 129.2, 127.3, 127, 126.9, 126.6, 125.5 (q, J = 3.9 Hz), 124.7
(q, J = 3.9 Hz), 123.6 (q, J = 272.8 Hz), 120.3, 115.6, 113.9, 55.7, 32.7; HRMS (ESI-TOF) m/z:
[M + H]+ Calcd for C23H18N2O2F3, 411.1315; found, 411.1324.
Methyl 5'-methoxy-2'-(3-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)-[1,1'-biphenyl]-3-carboxylate
(3v). Following the general experimental procedure, 3v was obtained as a colorless solid (60 mg,
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75% yield); Reaction time: 30 h at 90 C.Rf: 0.4 (1:2 EtOAc:Pet. ether); mp 118-120 C; H
NMR (400 MHz, CDCl3) δ (ppm) 8.25 (d, J = 7.94, 1H), 8.09 (s, 1H), 7.92 (d, J = 3.66, 1H),
7.78 (d, J = 3.66, 2H), 7.56-7.47 (m, 3H), 7.30 (d, J = 7.94, 1H), 7.11-7.06 (m, 2H), 3.93 (s, 3H),
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3.72 (s, 3H), 3.0 (s, 3H); C NMR (100 MHz, CDCl3) δ (ppm) 166.4, 162.2, 161, 156, 147.1,
140.6, 139.56, 134.2, 132.6, 130.7, 129.6, 129.1, 128.8, 127.4, 126.9, 126.6, 120.4, 115.5, 113.8,
55.6, 52, 32.7; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C24H21N2O4, 401.1496; found,
401.1505.
2-(5-methoxy-3'-nitro-[1,1'-biphenyl]-2-yl)-3-methylquinazolin-4(3H)-one (3w). Following the
general experimental procedure, 3w was obtained as a colorless solid (57 mg, 74% yield);
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Reaction time: 30 h at 90 C; Rf: 0.5 (1:1 EtOAc:Pet. ether); mp 158-160 C; H NMR (400
MHz, CDCl3) δ (ppm) 8.33 (s, 1H), 8.24 (d, J = 7.9 Hz, 1H), 8.12 (d, J = 7.9 Hz, 1H), 7.82-7.74
(m, 2H), 7.63 (d, J = 7.3, 1H), 7.55 (d, J = 8.5, 1H), 7.51 (t, J = 7.32, 1H), 7.39 (t, J = 7.93. 1H),
7.13 (d, J = 8.5, 1H), 7.07 (s, 1H), 3.95 (s, 3H), 3.07 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
(ppm) 162.2, 161.1, 155.2, 148.3, 146.9, 141.1, 139.2, 134.5, 134.3, 130.8, 129.7, 127.4, 127.2,
126.6, 126.7, 123.6, 122.9, 120.3, 115.8, 114.3, 55.7, 32.8; HRMS (ESI-TOF) m/z: [M + H]+
Calcd for C22H18N3O4, 388.1292; found, 388.1292.
2-(5-methoxy-4'-nitro-[1,1'-biphenyl]-2-yl)-3-methylquinazolin-4(3H)-one
(3x).
Following
general experimental procedure 3x was obtained as a colorless solid (53 mg, 68% yield);
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Reaction time: 36 h at 90 C; Rf: 0.5 (1:1 EtOAc:Pet. eher); mp 205-207 C; H NMR (400
MHz, CDCl3) δ (ppm) 8.26 (d, J = 7.94, 1H), 8.12 (d, J = 8.54, 2H), 7.82-7.72 , 2H), 7.58-7.49
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(m, 4H ), 7.13 (dd, J = 8.54, 1.83, 1H), 7.05 (s, 1H), 3.94 (s, 3H), 3.08 (s, 3H); C NMR (100
MHz, CDCl3) δ (ppm) 162.1, 161, 155.3, 147.3, 146.9, 146.1, 139.5, 134.5, 130.9, 129.4, 127.4,
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127.3, 126.8, 126.7, 123.9, 120.3, 115.8, 114.4, 55.7, 32.8; HRMS (ESI-TOF) m/z: [M + H]+
Calcd for C22H18N3O4, 388.1292; found, 388.1298.
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Supporting Information
The Supporting Information is available free of charge on the ACS Publications website at DOI:
Spectroscopic data (1H, 13C and HRMS spectra) of all new compounds (PDF)
AUTHOR INFORMATION
Corresponding Author
*E-mail: sb.mhaske@ncl.res.in
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
D.N.G. thanks, UGC-New Delhi, and A.B.V. thanks CSIR-New Delhi for the research
fellowships. S.B.M. gratefully acknowledges generous financial support from DST-SERB, and
CSIR-ORIGIN, New Delhi.
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