Iridium(III)-Catalyzed Alkynylation of 2-(Hetero)arylquinazolin-4-one Scaffolds via C-H Bond Activation

Article abstract of DOI:10.1021/acs.joc.8b02738

The directed C-H alkynylation of 2-(hetero)arylquinazolin-4-ones has been explored with the ethynylbenziodoxolone reagent TIPS-EBX employing an Ir(III) catalyst. Complementary conditions for either monoalkynylation or dialkynylation have been developed. Also demonstrated is the broad scope of this reaction and the compatibility of various functional groups such as ?F, ?Cl, ?Br, ?CF₃, ?OMe, ?NO₂, and alkyl, etc.

Full text of DOI:10.1021/acs.joc.8b02738

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Note
Iridium(III)-Catalysed Alkynylation of 2-
(Hetero)arylquinazolin-4-one Scaffolds via C–H Bond Activation
Rajendra Shankarrao Rohokale, Rupali G Kalshetti, and Chepuri V. Ramana
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b02738 • Publication Date (Web): 28 Jan 2019
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Iridium(III)-Catalysed Alkynylation of 2-(Hetero)arylquinazolin-4-one
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Scaffolds via C–H Bond Activation
Rajendra S. Rohokale,a * Rupali G. Kalshettia,b and Chepuri V. Ramanaa,b
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aCSIR–National Chemical Laboratory, Division of Organic Chemistry
Dr. Homi Bhabha Road, Pune–411008, India
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bAcademy of Scientific and Innovative Research, New Delhi-110025, India
TIPS
Het.
TIPS
O
N
O
N
O
N
Ir(III) (5 mol%)
Ir(III) (5 mol%)
AgSbF6 (10 mol%)
AgSbF6 (10 mol%)
NH
NH
H
H
NH
R'
R'
R'
TIPS-EBX
MeOH, rt, 16 h
TIPS-EBX, 1,2-DCE
70 oC, 12 h
Het
Het.
R
R
R
.
16 examples
26 examples
TIPS
ABSTRACT: The directed C–H alkynylation of 2-(hetero)arylquinazolin-4-ones has been
explored with the ethynylbenziodoxolone reagent TIPS-EBX employing an Ir(III)-catalyst.
Complementary conditions for either monoalkynylation or dialkynylation have been
developed. Also demonstrated is the broad scope of this reaction and the compatibility of
various functional groups such as -F, -Cl, -Br, -CF3, -OMe, -NO2 and alkyl etc.
“Alkyne” is a unique functional group in organic synthesis that allows the
introduction of a wide range of carbon and/or hetero atom centred functional groups that can
be easily transformed into carbo-/heterocycles of varying ring sizes.1 There are several
methods based on either functional group manipulation or cross-coupling reactions to
construct or introduce an alkyne unit. In recent years, there has been tremendous interest in
the catalytic alkynylation of C–H bonds to avoid pre-functionalization of the reacting
substrates.2 Indeed, the direct/directed alkynylation of sp2 C–H bonds is considered as a
reliable alternative to Sonogashira coupling.3,4 The directed alkynylation reactions occupy a
special role in this regard as they are regioselective and can be conducted even at room
temperature.4 A variety of functional groups such as amine, amide, anilide, imine, ester,
carboxylic acid, various heterocycles, hydroxyl and ketone groups have been employed as
directing groups for directed C–H bond alkynylations. The alkyne sources employed in this
pursuit include terminal alkynes,5 haloalkynes,6 borane alkynes,7 and alkynylated hypervalent
iodine reagents.8 There are various inorganic metal complexes (Pd, Ru, Rh, Ir, Co etc.) that
have been employed for the different types of C–H bond- (sp3, sp2 and sp) activation
processes. Amongst these, iridium complexes occupy a special place due to the high
reactivity of the Ir(III) species toward C–H bond cleavage.9 Coming to the Ir(III)-catalyzed
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directed alkynylations using EBX-based reagents (Scheme 1a),9a–9g the Jiang, Zeng, Li and
Xie groups reported respectively the carbonyl/carboxylate and pyrimidine directed ortho
C−H alkynylation of (hetero)aryl rings. The selective terminal alkynylation of 2-vinylanilines
has been reported by the Nachtsheim group. Li and co-workers on the other hand,
documented an Ir-catalyzed pyridine directed alkynylation of pendant aryls units of N1-aryl-
7-azaindol derivatives using TIPS-EBX. Very recently, Zhao and co-workers reported the
selective ortho-alkynylation of Cbz-protected benzylamines employing bromoalkynes as the
electrophilic alkynylating agents.
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As part of our ongoing program on C–H activation functionalization at ambient
temperatures employing [Ir]-complexes,10 the directed alkynylation of 2-arylquinazolinones
has been undertaken considering the fact that quinazolin-4-one is a privileged structural unit
widely found in natural products and in some approved/investigational drug candidates.11
Anticancer drugs like erlotinib, gefitinib and prazosin, which have been employed for curing
high blood pressure, anxiety and panic disorder are representative quinazolin-4-one based
marketed drugs.
Previous work
DG
DG
TIPS
H
(a)
Ir(III) catalysis
TIPS-EBX
= carbonyl,9a,b,d,l amine,9c pyrimidyl,9e,f pyridine9g
DG
O
N
O
N
[M] = Pd, Cu, Rh
Ru, Ir etc.
X
NH
NH
R'
R'
R
(b)
(c)
R
X
= OAc, NTs, Ar, alkene, halide etc.
Present work
TIPS
O
O
NH
NH
[IrCp*Cl2]2
R'
R'
N
N
Het.
Het.
R
R
TIPS
Scheme 1: Transition-metal catalyzed alkynylation reactions
The directed C–H functionalization of the pendant aryl ring in the 2-arylquinazolin-4-
one core has been well explored.12 C–H amination,13 arylation,14 alkenylation15 and cross
dehydrogenative coupling16 with acrylates and aceotxylation17 have been documented using
[Pd], [Ru], [Rh] and [Cu]-complexes (Scheme 1b). Coming to the reports with [Ir]-
complexes, there are very few in this regard. The mono-/bis-sulfamidation of the aryl ring in
2-arylquinazolin-4-one using sulfonyl azides was recently reported by Cui and co-workers
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and the reactions were carried out at elevated temperatures.13e This compilation on C–H
functionalization of 2-arylquinazolin-4-ones revealed that the corresponding directed
alkynylation via C–H bond functionalization on these scaffolds is missing. This prompted us
to conduct explorations in this direction.
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In this context, the preliminary experiments were conducted employing 2-
phenylquinazolin-4-one 1a (0.05 mmol) and TIPS-EBX 2 (0.06 mmol) as substrates and
[IrCp*Cl2]2 (5 mol%) and AgSbF6 (10 mol%) as the catalyst system. Initially, different
solvents were screened to see the feasibility of the proposed alkynylation. As shown in Table
1, the reaction outcome seems to be solvent dependent. When conducted in CH3CN at rt, the
reaction was sluggish and gave monoalkynylated quinazolin-4-one 3a (21%) along with
dialkynylated quinazolin-4-one 4a (10%) (Table 1, entry 1). The products yield was
improved when we switched to other aprotic polar solvents such as THF and dioxane.
However, both mono- and dialkynylated products were obtained in varying proportions
(Table 1, entries 2-3). Interestingly, when the reactions were conducted in protic solvents
such as methanol, ethanol and trifluroethanol at room temperature (Table 1, entries 4-8), the
dialkynylated product was not observed and the monoalkynylated product was obtained in
varying yields. It was found that methanol was a good choice of solvent for this reaction,
giving 3a in 89% isolated yield (entry 4). At this juncture, to check the possibility of carrying
out the dialkynylation exclusively, the reactions were conducted using 2.5 equiv of TIPS-
EBX (with respect to 1a) and different non-polar solvents such as toluene, dichloromethane
and dichloroethane were screened at different temperatures. As shown in Table 1, the best
results were obtained in dichloroethane at 70 °C, resulting in the dialkynylated product 4a in
94% isolated yield (entry 14). Control experiments revealed that the presence of the Ir-
complex is essential and that under similar conditions, the Rh(III) complex performed poorly
(entries 15–17).
Table 1: Optimization studiesa
TIPS
O
TIPS
O
NH
NH
table 1
I
N
O
+
N
3a
+
O
1a
2a
TIPS-EBX
TIPS
O
N
NH
Catalyst:
additive:
[A] = [IrCl2Cp*]2
[B] = [RhCl2Cp*]2 b = AgNTf2
a = AgSbF6
TIPS
4a
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entry catalyst/
additive
solvent temp. (°C) yieldb (%)
time (h)
rt/16
rt/12
3a
21
42
4a
10
8
1
2
3
4
5
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8
9
[A]/a
[A]/a
[A]/a
[A]/a
[A]/a
[A]/a
[A]/a
[A]/a
[A]/a
CH3CN
THF
Dioxane
MeOH
EtOH
HFIP
TFE
rt/16
rt/16
rt/16
rt/16
rt/16
44 trace
89 trace
52 trace
36 trace
30 trace
10
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12
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Toluene
DCM
DCE
rt/16
rt/16
rt/16
35
38
12
22
10 [B]/a
11 [A]/b
12 [A]/a
13 [A]/a
14 [A]/a
15 [B]/a
16 [B]/b
17 [B]/b
18 [A]/b
19 [A]/b
27 trace
DCE
rt/16
18
20
12
--
12
8
43
53
62
94
40
32
MeOH
DCM
DCE
DCE
DCE
DCE
DCE
DCE
70/12
70/12
70/12
70/12
70/12
70/12
70/12
70/12
trace 28c
8
24
68
38c
aReaction conditions: for entries 1-10: 0.05 mmol of 1a, 0.06 mmol of 2a, 5 mol % of
catalyst, 10 mol % of additive, dry solvent (1.0 mL), 16 h; for entries 12-19: 0.05 mmol of
1a, 0.125 mmol of 2a, 5 mol % of [IrCp*Cl2]2, 10 mol % of additives, dry solvent (1.0 mL),
12 h. bIsolated yields. cNaOAc (1.2 eq.) was used.
Having the complementary conditions for the selective mono- or dialkynylation in
hand, we proceeded to explore the scope of the current transformations employing diverse 2-
(hetero)arylquinazolin-4-one scaffolds (Scheme 2). Initially, we examined the scope of
substituents on the para-position (F, Cl, Br, Me, OMe, CF3; respectively 1b–1g), the meta-
position (F, Br, OMe; respectively 1h–1j), The selective mono-/dialkynylation of these
substrates 1b–1j proceeded smoothly with 2 under optimised conditions and provided the
corresponding monoalkynylated products 3b–3j (73–91%) and dialkynylated products 4b–4j
(67–96%) in good to excellent yields. The catalytic ortho-C–H alkynylation was not affected
by the steric hindrance of another ortho-substitution (1k–1m) Even when methoxy groups
were placed at the ortho- and para-positions, the alkynylation reaction proceeded smoothly
and provided the corresponding product 3n in 89% yield.
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TIPS
TIPS
O
O
N
TIPS-EBX
TIPS-EBX (2.5 equiv)
(1.2 equiv)
O
N
Ir(III) (5 mol%)
Ir(III) (5 mol%)
NH
NH
NH
TIPS
a
R'
R'
R'
N
AgSbF6 (10 mol%)
MeOH, rt, 16 h
AgSbF6 (10 mol%)
1,2-DCE, 70 oC, 12 h
R
R
R
3
1
4
TIPS
TIPS
O
TIPS
10
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O
TIPS
TIPS
O
O
N
O
NH
N
NH
NH
NH
NH
N
N
R
N
MeO
OMe
R
3u
(72%)
R
3n
, 89%
3a
3b
3c
3d
, 89%
R = H
R = F
R = Cl
R = Br
TIPS
TIPS
O
TIPS
, 81%
, 81%
, 84%
, 91%
, 83%
TIPS
b
O
R = Me 4o
, 86%
4a
4b
4c
4d
4e
, 94%
, 83%
, 81%
, 83%
, 96%
, 95%
R = H
NH
N
R = F
R = Br
R = NO2
4p
, 83%
, 80%
, 79%
R = F
NH
R = CH3 3e
4q
R
R = Cl
R = OMe
R = CF3
3f
4r
N
3g
R = Br
, 77%
X
TIPS
R = CH3
R = OMe
R = CF3
R = Me 3o
, 82%
, 75%
, 78%
, 70%
O
N
3v
X = O , 83%
TIPS
4f
4g
R = F
R = Br
R = NO2
3p
3q
3r
O
N
MeO
MeO
3w
X = S
, 79%
NH
, 88%
TIPS
NH
O
TIPS
NH
O
N
MeO
MeO
N
TIPS
NH
X
TIPS
O
R
4s
, 87%
TIPS
3x
X = N , 70%
X = S , 78%
3h
3i
R = F
R = Br
R = OMe 3j
, 73%
, 71%
, 74%
NH
c
3y
3s
, 62%
O
R
N
TIPS
O
N
TIPS
O
O
NH
TIPS
NH
NH
NH
N
TIPS
R = F
4h
, 76%
N
N
d
R = Br
R = OMe
4i
4j
, 67%
, 74%
R
Ph
3t
(84%)
4u
, 76%
TIPS
3z
(73%)
3k
R = F
R = Cl 3l
R = Br 3m
, 76%
, 74%
, 78%
Scheme 2: Ir(III)-catalysed C–H mono/dialkynylation of 2-(hetero)arylquinazolin-4-one
scaffolds; a82% on 1 g scale; b92% on 1 g scale; c14% of 4s was isolated; d12% of 3i was
isolated
Next, we examined the scope of substituents on the aryl ring of the quinazolin-4-one core by
employing the C7–(Me, F, Br or NO2) substituted 2-phenylquinazolin-4-ones 1o–1r. In all
the cases, the mono- and dialkynylation with 2 proceeded smoothly and provided the
corresponding monoalkynylated products 3o–3r (70–82%) and dialkynylated products 4o–4r
(79–86%) in very good yields. However, the monoalkynylation of 6,7-dimethoxy-2-
phenylquinazolin-4(3H)-one (1s) gave the corresponding monoalkynylated product 3s in 62%
yield, along with the dialkynylated product 4s in 14% yield.
The scope of the alkynylation reaction has been further examined by employing quinazolin-4-
ones 1t–1z having C2-napthyl and heteroaryl substituents. In case of 2-(1-napthyl)
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quinazolin-4(3H)-one (1t), the alkynylation happened as expected at the C2 of the naphthyl
ring and gave the corresponding product 3t in 84% yield. On the other hand, in case of the
isomeric 2-(2-napthyl) quinazolin-4(3H)-one (1u), the monoalkynylation took place
selectively at the C3 position instead of C1, resulting in the product 3u. This site selectivity
seems to originating from steric hindrance by the fused aromatic ring. The dialkynylation of
1u is also facile giving the 1,3-dialkynylated product 4u in 76% yield. Coming to the
alkynylation of 2-heteroaryl quinazolin-4-ones such as (2-furanyl; 1v), (2-thiophenyl; 1w),
(3-indolyl; 1x) and (3-benzothiophenyl; 1y), under the standard reaction conditions, the
alkynylation with 2 proceeded smoothly and gave the products 3v–3y in good yields (70–
83%). However, 2-(2-pyridyl)quinazolin-4-none was found to be intact under these reaction
conditions, suggesting the possible formation of a stable N,N’-bidentate iridium complex
which seems to inhibit further reactions. Interestingly, when (E)-2-styrylquinazolin-4(3H)-
one (1z) was employed as a substrate, under the standard reaction conditions, the
alkynylation with 2 proceeded selectively at the -carbon of the styrene and gave 3z in 73%
yield. To have a substrate for exploring the synthetic utility, the mono- and dialkynylation of
2-phenylquinazolin-4(3H)-one 1a has been carried out on 1 g scale using 5 mol % of the
iridium complex. The reactions proceeded smoothly to afford 3a (1.5 g) and 4a (2.3 g) in
82% and 92% yields respectively.
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The possibility of using R-EBX (R = n-octyl or phenyl) has been examined under both mono
and dialkylation conditions. At room temperature both substrates are intact and when heated
the R-EBX is undergoing an internal redox process resulting in the 2-oxo-2-(n-octyl or
phenyl)ethyl 2-iodobenzoate derivatives (See Scheme S1, SI).
O
N
O
N
N
TBAF, THF
NaH, DMF
0 oC-rt, 1 h 110 oC, 8 h
N
5a
5b
5c
(84%)
(41%)
O
3a
O
N
TIPS
Ph Ph-I, TBAF
NBS
PdCl2(PPh3)2
Br
N
Dioxane:H2O
(1:1)
CuI, THF
0 oC-rt, 1 h
N
N
5d
(74%)
(88%)
80 oC, 10 h
Scheme 3: Synthetic utility of 3a
Next, the synthetic utility of alkyne 3a (Scheme 3) was demonstrated by subjecting it
to cycloisomerization employing tetra-n-butylammonium fluoride (TBAF) and sodium
hydride (NaH) in DMF to obtain the complementary 5-exo-dig and 6-endo-dig cyclised
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products 5a and 5b with simultaneous TIPS deprotection respectively in 84% and 41% yield.
On the other hand, the electrophilic 6-endo-dig bromocyclization of compound 3a with N-
bromosuccinimide (NBS) resulted in the formation of 5c in 88% yield and the one-pot
desilylation with TBAF and [Pd]-catalyzed Sonogashira/hydroamination afforded cyclised
product 5d in 74% yield.
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Next, control experiments have been carried out to understand the course of the
reaction in general and the complementary mono vs. dialkynylation. Deuterium labelling
experiments employing CD3OD (10% in ortho-position of the phenyl group under heating in
DCE and no labelling when carried out in CD3OD at rt) revealed that the C−H bond cleavage
was a reversible process (see SI, Schemes S3 and S4). When the reaction was carried out in
the presence of 2 (Scheme S5, SI), no deuterium incorporation was observed in the recovered
1a, indicating that the alkynylation process proceeds faster than the deuteration. As expected,
the competitive reaction of an equimolar amount of 1h (3-flurophenyl), 1j (3-methoxphenyl)
and 2 under standard conditions gave 3h in 21% and 3j in 68% isolated yield respectively
(1:3.2 ratio) indicating that electron-rich phenyl groups undergo alkynylation faster (See
Scheme S6, SI).
O
NH
2
2
N
oxidative
addition
Irlll
*Cp
O
O
Path b
A
Path a
H+
NH
NH
N
N
1
*Cp Irlll
Irv
IPhCO2
(IrCp*(SbF6)2
AgCl
*Cp
R
I
B
D
R
O
AgSbF6
reductive
elimination
O
O
(IrCp*Cl2)2
O
N
NH
NH
N
Irv
1,2-R-group
migration
*Cp
Irlll
IPhCO2
IPhCO2
*Cp
R
E
3
C
R
Scheme 4: Mechanistic Proposal.
Based upon the previous reports,18–21 we propose the following tentative mechanistic
pathway (Scheme 4). The catalytic cycle starts with the formation of the monomeric
IrCp*(SbF6)2 complex, upon reaction of the dimeric iridium complex with AgSbF6. This
undergoes a coordinative C–H insertion with 2-arylquinazolin-4-one 1, resulting in the
cyclometalated Ir(III)-complex A.18 There are two possible pathways proposed for the
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transfer of the alkyne group from the TIPS-EBX to the aryl ring. In one path, the involvement
of an intermediate Ir(V) species occurs via the oxidative addition resulting in the alkynyl-
Ir(V) species B, which undergoes a reductive elimination, generating the key Ir(III)-alkyne
intermediate C (path a). 2b, 19 In another path, the complexation of the intermediate A with the
alkyne unit TIPS-EBX followed by a regioselective migratory insertion of alkyne results in
the intermediate D which, upon the α-elimination of 2-iodobenzoic acid, results in the iridium
vinylidene species E.2h,20,21b The intermediate E then undergoes a concerted R group-
migration followed by elimination, resulting in intermediate C, a species that is common in
both the pathways a and b. Finally, the alkynylated product 3 and the active Ir(III)-species are
generated by the dissociation of alkyne from C by complexing with 2-arylquinazolin-4-one 1,
which undergoes a C–H insertion to continue the catalytic cycle.
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In conclusion, [Ir]-catalysed ortho-alkynylation of 2-(hetero)arylquinazolin-4-ones
with TIPS-EBX has been established. In methanol, selective monoalkynylation has been
observed at room temperature. On the other hand, the dialkynylation could be conducted by
switching to 1,2-dichloroethane as a solvent and conducting the reaction at 70 °C. A wide-
range of mono-/dialkynylated quinazolin-4-ones have been synthesized in good to excellent
yields. Considering the ease of functionalizing the alkyne groups and the importance of the
quinazolin-4-one scaffold in new drug discovery programs, this late stage alkynylation
provides an attractive handle to synthesise molecules of therapeutic interest.
EXPERIMENTAL SECTION:
General Information:
The reactions were carried out in anhydrous solvents under argon atmosphere in oven–dried
glassware. All anhydrous solvents were distilled prior to use: dichloromethane, DCE and
CH3CN from CaH2; methanol from Mg cake; THF on Na/benzophenone. Commercial
reagents were used without any purification. Column chromatography was carried out by
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using silica gel (60–120, 100–200, 230–400 mesh). H and C NMR chemical shifts are
reported in ppm relative to chloroform-D (δ = 7.26) or TMS and coupling constants (J) are
reported in hertz (Hz). The following abbreviations have been used to designate signal
multiplicity: s = singlet, d = doublet, t = triplet, q = quartet, sxt = sextet, hept = septet, m =
multiplet, b = broad. High Resolution Mass Spectra (HRMS) were recorded on a Q Exactive
Hybrid Quadrupole Orbitrap Mass Spectrometer, where the mass analyser used for analysis is
orbitrap. Melting points were recorded on a digital microscopic melting apparatus and
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uncorrected. Infrared spectra were recorded on an ATR and only major peaks are reported in
cm-1. All starting quinazolin-2-ones21a and ethynyl benziodoxolones21b were prepared
according to well–known literature procedures.
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General procedure for iridium catalyzed C–H monoalkynylation of quinazolin-2-ones:
To a screw capped vial with a spinvane triangular–shaped Teflon stir bar were added aryl
quinqzolinone (0.2 mmol), TIPS-EBX (0.24 mmol), [IrCp*Cl2]2 (5 mol%, 8 mg), AgSbF6 (10
mol%, 7 mg), and methanol (3 mL) under air. The reaction mixture was stirred at room
temperature for 16 h. After completion, the reaction mixture was diluted with CH2Cl2 and
washed with sat. NaHCO3 followed by brine, dried (Na2SO4) and concentrated under reduced
pressure. The resulting crude was purified by column chromatography (5:1 petroleum
ether/EtOAc) to afford monoalkynylated quinazolin-2-ones 3.
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General procedure for iridium catalyzed C–H dialkynylation of quinazolin-2-ones: To a
screw capped vial with a spinvane triangular shaped teflon stir bar were added quinazolin-4-
one (0.2 mmol), TIPS-EBX (0.5 mmol), [IrCp*Cl2]2 (5 mol%, 8 mg), AgSbF6 (10 mol%, 7
mg) and 1,2-dichloroethane (3 mL) under air. The reaction mixture was stirred at 70 °C for
12 h. After completion, the reaction mixture was diluted with CH2Cl2 and washed with sat.
NaHCO3 followed by brine, dried (Na2SO4) and concentrated under reduced pressure. The
resulting crude was purified by column chromatography (9:1 petroleum ether/EtOAc) to
afford dilalkynylated quinazolin-4-ones 4.
2-(2-((Triisopropylsilyl)ethynyl)phenyl)quinazolin-4(3H)-one (3a).
The product was obtained as white solid; Yield: 72 mg (89%). Rf: 0.5 (5:1 petroleum
ether/EtOAc) Mp: 146–147 °C; IR(neat) max: 3022, 2944, 2142, 2863, 2150, 1671, 1563,
1368, 1213, 881, 769, 675 cm–1; 1H NMR (400 MHz, CDCl3) δ 10.76 (s, 1H), 8.34–8.23 (m,
2H), 7.84–7.72 (m, 2H), 7.69–7.57 (m, 1H), 7.54–7.45 (m, 3H), 1.38–0.99 (m, 21H); 13C{1H}
NMR (100 MHz, CDCl3) δ 161.4 (s), 151.2 (s), 149.1 (s), 134.8 (d), 134.5 (d), 133.7 (s),
130.8 (d), 130.0 (d), 129.2 (d), 128.0 (d), 127.0 (d), 126.5 (d), 121.4 (s), 120.6 (s), 104.1 (s),
100.4 (s), 18.6 (q, 6C), 11.2 (d, 3C); HRMS (ESI–TOF) m/z: [M + H]+ calcd for
C25H31N2OSi 403.2200, found 403.2206.
2-(4-Fluoro-2-((triisopropylsilyl)ethynyl)phenyl)quinazolin-4(3H)-one (3b).
The product was obtained as white solid; Yield: 68 mg (81%). Rf: 0.4 (5:1 petroleum
ether/EtOAc) Mp: 154–155 °C; IR(neat) max: 2944, 2861, 2155, 1655, 1462, 1370, 1223,
876, 768, 637 cm–1; 1H NMR (400 MHz, CDCl3) δ 10.71 (s, 1H), 8.42–8.10 (m, 2H), 7.85–
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7.71 (m, 2H), 7.59–7.43 (m, 1H), 7.32 (dd, J = 8.7, 2.6 Hz, 1H), 7.22 (ddd, J = 8.9, 7.8, 2.7
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Hz, 1H), 1.30–1.06 (m, 21H); C{1H} NMR (100 MHz, CDCl3) δ 163.6 (ds, JC–F = 253.7
Hz), 161.3 (s), 150.3 (s), 149.0 (s), 134.6 (d), 132.6 (dd, 3JC-F = 9.2 Hz), 130.0 (ds, 4JC-F = 2.9
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Hz), 128.0 (d), 127.1 (d), 126.5 (d), 122.6 (ds, JC-F = 10.1 Hz), 121.3 (s), 121.2 (dd, JC-F
=
23.6 Hz), 117.1 (dd, 2JC-F = 21.6 Hz), 102.9 (s), 102.1 (s), 18.6 (q, 6C), 11.1 (d, 3C); HRMS
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(ESI–TOF) m/z: [M + H]+ calcd for C25H30FN2OSi 421.2106, found 421.2110.
2-(4-Chloro-2-((triisopropylsilyl)ethynyl)phenyl)quinazolin-4(3H)-one (3c).
The product was obtained as white solid; Yield: 70 mg (81%). Rf: 0.5 (5:1 petroleum
ether/EtOAc) Mp: 151–152 °C; IR(neat) max: 2948, 2860, 2152, 1670, 1463, 1368, 1228,
860, 732, 660 cm–1; 1H NMR (400 MHz, CDCl3) δ 10.77 (s, 1H), 8.29 (dd, J = 8.2, 3.2 Hz,
2H), 7.79 (d, J = 3.8 Hz, 2H), 7.61 (d, J = 2.0 Hz, 1H), 7.49 (ddd, J = 8.6, 6.5, 2.9 Hz, 2H),
1.35–1.04 (m, 21H); 13C{1H} NMR (100 MHz, CDCl3) δ 161.3 (s), 150.2 (s), 149.0 (s), 137.0
(s), 134.7 (d), 134.2 (d), 131.9 (s), 131.5 (d), 129.6 (d), 128.0 (d), 127.2 (d), 126.5 (d), 121.9
(s), 121.4 (s), 102.8 (s), 102.3 (s), 18.6 (q, 6C), 11.1 (d, 3C); HRMS (ESI–TOF) m/z: [M +
H]+ calcd for, C25H30ClN2OSi 437.1810 found 437.1816.
2-(4-Bromo-2-((triisopropylsilyl)ethynyl)phenyl)quinazolin-4(3H)-one (3d).
The product was obtained as white solid; Yield: 80 mg (84%). Rf: 0.5 (5:1 petroleum
ether/EtOAc) Mp: 153–154 °C; IR(neat) max: 3281, 2938, 2862, 2146, 1691, 1467, 1372,
1213, 880, 727, 634 cm–1; 1H NMR (400 MHz, CDCl3) δ 10.71 (s, 1H), 8.30 (dt, J = 7.9, 1.1
Hz, 1H), 8.23 (d, J = 8.6 Hz, 1H), 7.89–7.74 (m, 3H), 7.64 (dd, J = 8.6, 2.1 Hz, 1H), 7.57–
13
7.41 (m, 1H), 1.26–0.93 (m, 21H); C{1H} NMR (100 MHz, CDCl3) δ 161.2 (s), 150.2 (s),
149.0 (s), 137.1 (d), 134.7 (d), 132.6 (d), 132.3 (s), 131.5 (d), 128.1 (d), 127.2 (d), 126.5 (d),
125.2 (s), 122.1 (s), 121.4 (s), 102.7 (s), 102.5 (s), 18.6 (q, 6C), 11.1 (d, 3C); HRMS (ESI–
TOF) m/z: [M + H]+ calcd for C25H30BrN2OSi 481.1305, found 481.1312.
2-(4-Methyl-2-((triisopropylsilyl)ethynyl)phenyl)quinazolin-4(3H)-one (3e).
The product was obtained as white solid; Yield: 76 mg (91%). Rf: 0.5 (5:1 petroleum
ether/EtOAc) Mp: 149–150 °C; IR(neat) max: 2944, 2861, 2158, 1680, 1571, 1463, 1369,
1222, 840, 710, 669 cm–1; 1H NMR (400 MHz, CDCl3) δ 10.79 (s, 1H), 8.30 (d, J = 7.7 Hz,
1H), 8.23 (d, J = 8.2 Hz, 1H), 7.86–7.64 (m, 2H), 7.54–7.39 (m, 2H), 7.31 (dd, J = 8.2, 1.0
13
Hz, 1H), 2.41 (s, 3H), 1.76–0.81 (m, 21H); C{1H} NMR (100 MHz, CDCl3) δ 161.4 (s),
151.2 (s), 149.2 (s), 141.4 (s), 135.2 (d), 134.5 (d), 130.7 (s), 130.3 (d), 130.0 (d), 128.0 (d),
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126.7 (d), 126.5 (d), 121.3 (s), 120.2 (s), 104.5 (s), 100.1 (s), 21.1 (q), 18.7 (q, 6C), 11.2 (d,
3C); HRMS (ESI–TOF) m/z: [M + H]+ calcd for C26H33N2OSi 417.2357, found 417.2362.
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The product was obtained as white solid; Yield: 72 mg (83%). Rf: 0.5 (5:1 petroleum
ether/EtOAc) Mp: 150–151 °C; IR(neat) max: 2937, 2859, 2143, 1685, 1578, 1460, 1370,
1226, 726, 664 cm–1; 1H NMR (400 MHz, CDCl3) δ 10.81 (s, 1H), 8.32 (d, J = 8.9 Hz, 1H),
8.30–8.26 (m, 1H), 7.79–7.72 (m, 2H), 7.45 (ddd, J = 8.2, 6.0, 2.3 Hz, 1H), 7.09 (d, J = 2.6
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Hz, 1H), 7.04 (dd, J = 8.9, 2.7 Hz, 1H), 3.89 (s, 3H), 1.29–1.10 (m, 21H); C{1H} NMR
(100 MHz, CDCl3) δ 161.4 (s), 161.3 (s), 150.9 (s), 149.3 (s), 134.46 (d), 132.0 (d), 127.8 (d),
126.6 (d), 126.5 (d), 125.9 (s), 121.6 (s), 121.2 (s), 119.3 (d), 115.8 (d), 104.2 (s), 100.6 (s),
55.6 (q), 18.7 (q, 6C), 11.2 (d, 3C); HRMS (ESI–TOF) m/z: [M + H]+ calcd for
C26H33N2O2Si 433.2306, found 433.2310.
2-(4-(Trifluoromethyl)-2-((triisopropylsilyl)ethynyl)phenyl)quinazolin-4(3H)-one (3g).
The product was obtained as white solid; Yield: 74 mg (77%). Rf: 0.5 (5:1 petroleum
ether/EtOAc) Mp: 169–170 °C; IR(neat) max: 2922, 2862, 2140, 1668, 1564, 1464, 1330,
1120, 899, 774, 660 cm–1; 1H NMR (400 MHz, CDCl3) δ 10.78 (s, 1H), 8.42 (d, J = 8.3 Hz,
1H), 8.31 (d, J = 8.0 Hz, 1H), 7.86 (s, 1H), 7.84–7.77 (m, 2H), 7.74 (dd, J = 8.3, 1.3 Hz, 1H),
7.58–7.47 (m, 1H), 1.46–0.86 (m, 21H); 13C{1H} NMR (100 MHz, CDCl3) δ 161.3 (s), 149.9
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(s), 148.8 (s), 136.8 (s), 134.8 (d), 133.0 (qs, JC-F = 33.8 Hz), 131.43 (qd, JC-F = 11.0 Hz),
130.8 (d), 128.2 (d), 127.5 (d), 126.6 (d), 125.6 (qd, 3JC-F = 10.3 Hz), 124.5 (qs, 1JC-F = 273.0
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Hz), 121.5 (ds, JC-F = 2.9 Hz), 121.5 (s), 107.5 (s), 102.6 (s), 18.6 (q, 6C), 11.1 (d, 3C).
HRMS (ESI–TOF) m/z: [M + H]+ calcd for C26H30F3N2OSi 471.2074, found 471.2081.
2-(5-Fluoro-2-((triisopropylsilyl)ethynyl)phenyl)quinazolin-4(3H)-one (3h).
The product was obtained as white solid; Yield: 62 mg (73%). Rf: 0.5 (5:1 petroleum
ether/EtOAc) Mp: 136–137 °C; IR(neat) max: 3296, 2943, 2862, 2150, 1685, 1554, 1462,
1
1285, 844, 721, 672 cm–1; H NMR (400 MHz, CDCl3) δ 10.86 (s, 1H), 8.30 (d, J = 7.9 Hz,
1H), 8.07 (d, J = 7.9 Hz, 1H), 7.89–7.71 (m, 2H), 7.57–7.40 (m, 2H), 7.36–7.20 (m, 1H),
1.31–1.02 (m, 21H); 13C{1H} NMR (100 MHz, CDCl3) δ 164.2 (ds, 1JC-F = 252.7 Hz), 161.4
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(s), 150.2 (s), 148.9 (s), 135.5 (s), 134.7 (d), 130.0 (dd, JC-F = 8.7 Hz), 128.1 (d), 127.2 (d),
126.5 (d), 125.5 (dd, 4JC-F = 3.4 Hz), 121.4 (s), 117.8 (dd, 2JC-F = 21.8 Hz), 110.0 (ds, 2JC-F
=
18.8 Hz), 107.2 (s), 96.5 (s), 18.6 (q, 6C), 11.1 (d, 3C); HRMS (ESI–TOF) m/z: [M + H]+
calcd for C25H30FN2OSi 421.2106, found 421.2107.
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2-(5-Bromo-2-((triisopropylsilyl)ethynyl)phenyl)quinazolin-4(3H)-one (3i).
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The product was obtained as white solid; Yield: 68 mg (71%). Rf: 0.5 (5:1 petroleum
ether/EtOAc) Mp: 164–165 °C; IR(neat) max: 3024, 2939, 2861, 2152, 1665, 1603, 1465,
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1291, 878, 767, 658 cm–1; H NMR (400 MHz, CDCl3) δ 10.82 (s, 1H), 8.51 (d, J = 2.1 Hz,
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1H), 8.31 (d, J = 7.7 Hz, 1H), 7.86–7.75 (m, 2H), 7.61 (dd, J = 8.3, 2.1 Hz, 1H), 7.54–7.48
(m, 2H), 1.23–1.18 (m, 21H); 13C{1H} NMR (100 MHz, CDCl3) δ 161.3 (s), 149.7 (s), 148.9
(s), 136.0 (d), 134.9 (s), 134.7 (d), 133.9 (d), 132.9 (d), 128.6 (d), 127.32 (d), 126.5 (d), 123.6
(s), 121.4 (s), 119.3 (s), 103.2 (s), 102.2 (s), 18.6 (q, 6C), 11.1 (d, 3C); HRMS (ESI–TOF)
m/z: [M + H]+ calcd for C25H30BrN2OSi 481.1305, found 481.1313.
2-(5-Methoxy-2-((triisopropylsilyl)ethynyl)phenyl)quinazolin-4(3H)-one (3j).
The product was obtained as white solid; Yield: 64 mg (74%). Rf: 0.6 (5:1 petroleum
ether/EtOAc) Mp: 122–123 °C; IR(neat) max: 2938, 2862, 2150, 1664, 1591, 1463, 1241,
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1025, 877, 773, 668 cm–1; H NMR (400 MHz, CDCl3) δ 11.00 (s, 1H), 8.30 (d, J = 7.9 Hz,
1H), 7.84–7.74 (m, 3H), 7.56 (d, J = 8.6 Hz, 1H), 7.48 (t, J = 7.3 Hz, 1H), 7.01 (dd, J = 8.6,
2.5 Hz, 1H), 3.91 (s, 3H), 1.22–1.01 (m, 21H); 13C{1H} NMR (100 MHz, CDCl3) δ 161.6 (s),
160.0 (s), 151.1 (s), 149.1 (s), 136.3 (d), 135.1 (s), 134.5 (d), 128.0 (d), 127.0 (d), 126.5 (d),
121.4 (s), 117.8 (d), 114.1 (d), 112.9 (s), 104.2 (s), 98.4 (s), 55.7 (q), 18.6 (q, 6C), 11.2 (d,
3C); HRMS (ESI–TOF) m/z: [M + H]+ calcd for C26H33N2O2Si 433.2306, found 433.2311.
2-(2-Fluoro-6-((triisopropylsilyl)ethynyl)phenyl)quinazolin-4(3H)-one (3k).
The product was obtained as white solid; Yield: 62 mg (76%). Rf: 0.4 (5:1 petroleum
ether/EtOAc) Mp: 153–154 °C; IR(neat) max: 2941, 2863, 2154, 1665, 1467, 1371, 1221,
871, 761, 648 cm–1; 1H NMR (400 MHz, CDCl3) δ 10.33 (s, 1H), 8.25 (d, J = 8.0 Hz, 1H),
7.91–7.71 (m, 2H), 7.52 (ddd, J = 8.1, 4.8, 3.5 Hz, 1H), 7.47–7.37 (m, 2H), 7.24–7.11 (m,
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1H), 0.97–0.74 (m, 21H); C{1H} NMR (100 MHz, CDCl3) δ 162.3 (s), 159.9 (ds, JC-F
=
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251.2 Hz), 148.9 (s), 147.6 (s), 134.6 (d), 131.7 (dd, JC-F = 9.2 Hz), 129.3 (dd, JC-F = 3.3
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Hz), 128.1 (d), 127.4 (d), 126.4 (d), 125.0 (s), 124.6 (ds, JC-F = 16.4 Hz), 121.4 (s), 116.4
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(dd, JC-F = 21.6 Hz), 102.2 (ds, JC-F = 3.8 Hz), 97.9 (s), 18.4 (q, 6C), 11.0 (d, 3C); HRMS
(ESI–TOF) m/z: [M + H]+ calcd for C25H30FN2OSi 421.2106, found 421.2107.
2-(2-Chloro-6-((triisopropylsilyl)ethynyl)phenyl)quinazolin-4(3H)-one (3l).
The product was obtained as white solid; Yield: 64 mg (74%). Rf: 0.5 (5:1 petroleum
ether/EtOAc) Mp: 184–185 °C; IR(neat) max: 2943, 2864, 2153, 1670, 1462, 1379, 1228,
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860, 738, 661 cm–1; 1H NMR (400 MHz, CDCl3) δ 10.47 (s, 1H), 8.23 (d, J = 8.1 Hz, 1H),
7.86–7.68 (m, 2H), 7.57–7.48 (m, 2H), 7.46 (dd, J = 8.2, 1.3 Hz, 1H), 7.43–7.34 (m, 1H),
0.87–0.80 (m, 21H); 13C{1H} NMR (100 MHz, CDCl3) δ 162.6 (s), 150.2 (s), 148.9 (s), 135.6
(s), 134.6 (d), 133.1 (s), 131.4 (d), 130.9 (d), 129.7 (d), 128.1 (d), 127.4 (d), 126.3 (d), 125.2
(s), 121.4 (s), 102.3 (s), 97.8 (s), 18.3 (q, 6C), 10.9 (d, 3C); HRMS (ESI–TOF) m/z: [M + H]+
calcd for, C25H30ClN2OSi 437.1810 found 437.1814.
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2-(2-Bromo-6-((triisopropylsilyl)ethynyl)phenyl)quinazolin-4(3H)-one (3m).
The product was obtained as white solid; Yield: 75 mg (78%). Rf: 0.5 (5:1 petroleum
ether/EtOAc) Mp: 194–195 °C; IR(neat) max: 3222, 2940, 2862, 2148, 1666, 1468, 1370,
1220, 882, 730, 636 cm–1; 1H NMR (400 MHz, CDCl3) δ 9.83 (s, 1H), 8.26 (dd, J = 8.4, 4.5
Hz, 1H), 7.79 (d, J = 3.6 Hz, 2H), 7.64 (d, J = 8.1 Hz, 1H), 7.58 (dd, J = 7.8, 1.1 Hz, 1H),
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7.55–7.49 (m, 1H), 7.32 (t, J = 8.0 Hz, 1H), 1.04–0.71 (m, 21H); C{1H} NMR (100 MHz,
CDCl3) δ 161.9 (s), 151.1 (s), 148.8 (s), 137.4 (s), 134.6 (d), 132.8 (d), 131.9 (d), 131.1 (d),
128.1 (d), 127.4 (d), 126.4 (d), 125.2 (s), 121.8 (s), 121.5 (s), 102.2 (s), 98.0 (s), 18.4 (q, 6C),
11.0 (d, 3C); HRMS (ESI–TOF) m/z: [M + H]+ calcd for C25H30BrN2OSi 481.1305, found
481.1309.
2-(2,4-Dimethoxy-6-((triisopropylsilyl)ethynyl)phenyl)quinazolin-4(3H)-one (3n).
The product was obtained as white solid; Yield: 82 mg (89%). Rf: 0.5 (5:1 petroleum
ether/EtOAc) Mp: 129–130 °C; IR(neat) max: 2922, 2860, 2145, 1671, 1596, 1387, 1216,
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1021, 861, 734, 643 cm–1; H NMR (400 MHz, CDCl3) δ 11.3 (s, 1H), 8.55 (d, J = 7.9 Hz,
1H), 8.20 (s, 1H), 8.11–7.97 (m, 2H), 7.72 (ddd, J = 8.2, 6.7, 1.6 Hz, 1H), 7.51 (s, 1H), 4.29
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(s, 3H), 4.23 (s, 3H), 1.58–1.31 (m, 21H); C{1H} NMR (100 MHz, CDCl3) δ 161.4 (s),
150.9 (s), 150.7 (s), 150.0 (s), 149.2 (s), 134.5 (d), 127.8 (d), 126.7 (d), 126.6 (s), 126.5 (d),
121.2 (s), 116.2 (d), 113.2 (s), 112.1 (d), 104.5 (s), 99.5 (s), 56.2 (q), 56.2 (q), 18.7 (q, 6C),
11.2 (d, 3C); HRMS (ESI–TOF) m/z: [M + H]+ calcd for C27H35N2O3Si 463.2411, found
463.2419.
7-Methyl-2-(2-((triisopropylsilyl)ethynyl)phenyl)quinazolin-4(3H)-one (3o).
The product was obtained as white solid; Yield: 68 mg (82%). Rf: 0.5 (5:1 petroleum
ether/EtOAc) Mp: 118–119 °C; IR(neat) max: 2935, 2859, 2155, 1655, 1610, 1456, 1216,
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880, 791, 666 cm–1; H NMR (400 MHz, CDCl3) δ 10.59 (s, 1H), 8.29 (dd, J = 7.4, 1.5 Hz,
1H), 8.19 (d, J = 8.1 Hz, 1H), 7.65 (dd, J = 7.1, 1.6 Hz, 1H), 7.60 (s, 1H), 7.55–7.45 (m, 2H),
7.31 (d, J = 8.1 Hz, 1H), 2.52 (s, 3H), 1.49–0.76 (m, 21H); 13C{1H} NMR (100 MHz, CDCl3)
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δ 161.2 (s), 151.2 (s), 149.3 (s), 145.5 (s), 134.8 (d), 133.7 (s), 130.68 (d), 130.0 (d), 129.2
(d), 128.5 (d), 127.8 (d), 126.3 (d), 120.5 (s), 119.0 (s), 104.2 (s), 100.5 (s), 21.9 (q), 18.6 (q,
6C), 11.2 (d, 3C); HRMS (ESI–TOF) m/z: [M + H]+ calcd for C26H33N2OSi 417.2357, found
417.2352.
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7-Fluoro-2-(2-((triisopropylsilyl)ethynyl)phenyl)quinazolin4(3H)-one(3p).
The product was obtained as white solid; Yield: 63 mg (75%). Rf: 0.5 (5:1 petroleum
ether/EtOAc) Mp: 121–122 °C; IR(neat) max: 3283, 2944, 2861, 2143, 1687, 1576, 1373,
1285, 879, 765, 676 cm–1; 1H NMR (400 MHz, CDCl3) δ 10.92 (brs, 1H), 8.33–8.17 (m, 2H),
7.69–7.56 (m, 1H), 7.54–7.48 (m, 2H), 7.43 (d, J = 9.7 Hz, 1H), 7.24–7.13 (m, 1H), 1.31–
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0.84 (m, 21H); C{1H} NMR (100 MHz, CDCl3) δ 166.7 (ds, JC-F = 254.2 Hz), 160.7 (s,),
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152.4 (s), 151.3 (ds, JC-F = 13.2 Hz), 134.9 (d), 133.3 (ds, JC-F = 3.1 Hz), 131.0 (d), 130.0
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(d), 129.2 (d), 129.1 (dd, JC–F = 11.0 Hz), 120.7 (s), 118.1 (s,), 115.7 (dd, JC–F = 23.6 Hz),
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113.3 (dd, JC–F = 21.8 Hz), 104.1 (s), 100.7 (s), 18.6 (q, 6C), 11.2 (d, 3C); F NMR (377
MHz, CDCl3) δ –103.2.; HRMS (ESI–TOF) m/z: [M + H]+ calcd for C25H30FN2OSi
421.2106, found 421.2100.
7-Bromo-2-(2-((triisopropylsilyl)ethynyl)phenyl)quinazolin-4(3H)-one (3q).
The product was obtained as white solid; Yield: 75 mg (78%). Rf: 0.5 (5:1 petroleum
ether/EtOAc) Mp: 124–125 °C; IR(neat) max: 3308, 2941, 2143, 2864, 1689, 1587, 1462,
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1234, 880, 769, 659 cm–1; H NMR (400 MHz, CDCl3) δ 10.86 (s, 1H), 8.31 (d, J = 8.1 Hz,
1H), 8.14 (d, J = 8.5 Hz, 1H), 7.98 (d, J = 1.8 Hz, 1H), 7.70–7.62 (m, 1H), 7.58 (dd, J = 8.5,
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1.9 Hz, 1H), 7.56–7.45 (m, 2H), 1.56–0.89 (m, 21H); C{1H} NMR (100 MHz, CDCl3) δ
160.8 (s), 152.2 (s), 150.1 (s), 135.0 (d), 133.0 (s), 131.1 (d), 130.8 (d), 130.3 (d), 130.1 (d),
129.3 (d), 129.3 (s), 127.9 (d), 120.5 (s), 120.2 (s), 104.1 (s), 101.1 (s), 18.6 (q, 6C), 11.2 (d,
3C); HRMS (ESI–TOF) m/z: [M + H]+ calcd for C25H30BrN2OSi 481.1305, found 481.1298.
7-Nitro-2-(2-((triisopropylsilyl)ethynyl)phenyl)quinazolin-4(3H)-one (3r).
The product was obtained as yellow solid; Yield: 62 mg (70%). Rf: 0.4 (5:1 petroleum
ether/EtOAc) Mp: 147–148 °C; IR(neat) max: 3261, 2933, 2862, 2150, 1702, 1576, 1347,
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1228, 880, 731, 676 cm–1; H NMR (500 MHz, CDCl3) δ 11.16 (s, 1H), 8.64 (d, J = 2.1 Hz,
1H), 8.46 (d, J = 8.7 Hz, 1H), 8.44–8.39 (m, 1H), 8.24 (dd, J = 8.7, 2.1 Hz, 1H), 7.73–7.66
(m, 1H), 7.62–7.43 (m, 2H), 1.26–1.03 (m, 21H); 13C{1H} NMR (125 MHz, CDCl3) δ 160.1
(s), 153.0 (s, 2C), 151.8 (s), 149.7 (s), 135.2 (d), 132.2 (s), 131.6 (d), 130.2 (d), 129.5 (d),
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128.4 (d), 125.5 (s), 123.6 (d), 120.5 (d), 104.0 (s), 101.8 (s), 18.6 (q, 6C), 11.2 (d, 3C);
HRMS (ESI–TOF) m/z: [M + H]+ calcd for C25H30N3O3Si 448.2051, found 448.2047.
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The product was obtained as white solid; Yield: 58 mg (62%). Rf: 0.5 (5:1 petroleum
ether/EtOAc) Mp: 129–130 °C; IR(neat) max: 2942, 2861, 2148, 1656, 1569, 1385, 1269,
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1218, 1080, 980, 878, 668 cm–1; H NMR (400 MHz, CDCl3) δ 10.65 (s, 1H), 8.33 (dd, J =
7.6, 1.5 Hz, 1H), 7.70–7.66 (m, 2H), 7.57–7.48 (m, 2H), 7.29 (s, 1H), 4.06 (s, 3H), 4.04 (s,
3H), 1.33–1.10 (m, 21H); 13C{1H} NMR (100 MHz, CDCl3) δ 160.7 (s), 155.1 (s), 149.9 (s),
149.3 (s), 145.4 (s), 134.9 (d), 133.5 (s), 130.6 (d), 129.7 (d), 129.3 (d), 120.3 (s), 114.7 (s),
108.5 (d), 105.5 (d), 104.3 (s), 100.5 (s), 56.4 (q), 56.3 (q), 18.7 (q, 6C), 11.2 (d, 3C); HRMS
(ESI–TOF) m/z: [M + H]+ calcd for C27H35N2O3Si 463.2411, found 463.2408.
2-(2-((Triisopropylsilyl)ethynyl)naphthalen-1yl)quinazolin-4(3H)-one (3t).
The product was obtained as yellow solid; Yield: 76 mg (84%). Rf: 0.6 (5:1 petroleum
ether/EtOAc) Mp: 202–203 °C; IR(neat) max: 2943, 2858, 2142, 1662, 1466, 1371, 1221,
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1H), 7.92 (d, J = 8.5 Hz, 1H), 7.86 (d, J = 7.5 Hz, 1H), 7.84–7.79 (m, 2H), 7.76 (d, J = 8.8
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Hz, 1H), 7.63 (d, J = 8.5 Hz, 1H), 7.58–7.45 (m, 3H), 1.06–0.78 (m, 21H); C{1H} NMR
(100 MHz, CDCl3) δ 162.0 (s), 151.6 (s), 149.0 (s), 134.7 (d), 134.5 (s), 132.9 (s), 130.7 (s),
130.2 (d), 128.7 (d), 128.3 (d), 128.1 (d), 128.0 (d), 127.3 (d), 127.2 (d), 126.4 (d), 124.9 (d),
121.5 (s), 121.0 (s), 103.9 (s), 97.9 (s), 18.4 (q, 6C), 11.0 (d, 3C); HRMS (ESI–TOF) m/z: [M
+ H]+ calcd for C29H33N2OSi 453.2357, found 453.2361.
2-(3-((Triisopropylsilyl)ethynyl)naphthalen-2-yl)quinazolin-4(3H)-one (3u).
The product was obtained as white solid; Yield: 64 mg (72%). Rf: 0.6 (5:1 petroleum
ether/EtOAc) Mp: 194–195 °C; IR(neat) max: 2941, 2861, 2148, 1665, 1602, 1462, 1370,
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8.31 (d, J = 7.8 Hz, 1H), 8.17 (s, 1H), 7.97 (d, J = 7.1 Hz, 1H), 7.86 (d, J = 7.9 Hz, 2H),
7.83–7.74 (m, 1H), 7.65–7.53 (m, 2H), 7.50 (t, J = 7.4 Hz, 1H), 1.22–1.09 (m, 21H); 13C{1H}
NMR (100 MHz, CDCl3) δ 161.5 (s), 151.6 (s), 149.3 (s), 135.3 (d), 134.3 (d), 133.6 (s),
132.5 (s), 130.8 (d), 130.3 (s), 129.0 (d), 128.5 (d), 128.0 (d), 127.9 (d), 127.4 (d), 126.9 (d),
126.5 (d), 121.3 (s), 117.0 (s), 104.5 (s), 99.1 (s), 18.7 (q, 6C), 11.2 (d, 3C); HRMS (ESI–
TOF) m/z: [M + H]+ calcd for C29H33N2OSi 453.2357, found 453.2355.
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2-(3-((Triisopropylsilyl)ethynyl)furan-2-yl)quinazolin-4(3H)-one (3v).
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The product was obtained as yellow solid; Yield: 64 mg (83%). Rf: 0.6 (5:1 petroleum
ether/EtOAc) Mp: 148–149 °C; IR(neat) max: 2924, 2858, 2139, 1655, 1370, 1211, 881, 748,
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642 cm–1; H NMR (400 MHz, CDCl3) δ 10.37 (s, 1H), 8.29 (dd, J = 8.0, 1.1 Hz, 1H), 7.84
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(dd, J = 8.2, 0.7 Hz, 1H), 7.77 (ddd, J = 8.3, 7.1, 1.6 Hz, 1H), 7.62 (d, J = 1.9 Hz, 1H), 7.48
(ddd, J = 8.1, 7.1, 1.2 Hz, 1H), 6.66 (d, J = 1.9 Hz, 1H), 1.31–1.13 (m, 21H); 13C{1H} NMR
(100 MHz, CDCl3) δ 160.7 (s), 148.7 (s), 146.7 (s), 145.2 (d), 143.0 (s), 134.8 (d), 128.1 (d),
127.2 (d), 126.7 (d), 121.8 (s), 115.6 (d), 110.4 (s), 103.9 (s), 96.9 (s), 18.8 (q, 6C), 11.2 (d,
3C); HRMS (ESI–TOF) m/z: [M + H]+ calcd for C23H29N2O2Si 393.1993, found 393.1995.
2-(3-((Triisopropylsilyl)ethynyl)thiophen-2-yl)quinazolin-4(3H)-one (3w).
The product was obtained as yellow solid; Yield: 64 mg (79%). Rf: 0.5 (5:1 petroleum
ether/EtOAc) Mp: 136–137 °C; IR(neat) max: 2944, 2861, 2141, 1689, 1464, 1348, 1212,
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769, 710, 668 cm–1; H NMR (400 MHz, CDCl3) δ 11.03 (s, 1H), 8.28 (d, J = 7.9 Hz, 1H),
7.82–7.61 (m, 2H), 7.49–7.41 (m, 2H), 7.18 (d, J = 5.1 Hz, 1H), 1.36–1.12 (m, 21H);
13C{1H} NMR (100 MHz, CDCl3) δ 160.9 (s), 148.9 (s), 146.8 (s), 138.5 (s), 134.6 (d), 132.5
(d), 129.8 (d), 127.6 (d), 126.7 (d), 126.6 (d), 121.6 (s), 121.2 (s), 102.3 (s), 100.4 (s), 18.7
(q, 6C), 11.2 (d, 3C); HRMS (ESI–TOF) m/z: [M + H]+ calcd for C23H29N2OSSi 409.1764,
found 409.1765.
2-(2-((Triisopropylsilyl)ethynyl)-1H-indol-3-yl)quinazolin-4(3H)-one (3x).
The product was obtained as yellow solid; Yield: 60 mg (70%). Rf: 0.5 (5:1 petroleum
ether/EtOAc) Mp: 209–210 °C; IR(neat) max: 3254, 2937, 2862, 2139, 1661, 1584, 1418,
1235, 874, 718, 674 cm–1; 1H NMR (400 MHz, CDCl3) δ 10.52 (brs, 1H), 8.89 (d, J = 7.4 Hz,
1H), 8.70 (brs, 1H), 8.30 (dd, J = 7.9, 1.1 Hz, 1H), 7.85 (d, J = 7.6 Hz, 1H), 7.76 (ddd, J =
8.3, 7.1, 1.6 Hz, 1H), 7.43 (ddd, J = 8.1, 7.2, 1.2 Hz, 1H), 7.40–7.31 (m, 3H), 1.36–1.11 (m,
21H); 13C{1H} NMR (100 MHz, CDCl3) δ 161.6 (s), 149.9 (s), 148.5 (s), 135.8 (s), 134.4 (d),
127.9 (d), 126.5 (d), 126.0 (d), 125.6 (s), 125.5 (d), 123.9 (d), 122.7 (d), 121.3 (s), 118.4 (s),
113.4 (s), 110.8 (d), 105.9 (s), 96.8 (s), 18.7 (q, 6C), 11.2 (d, 3C); HRMS (ESI–TOF) m/z:
[M + H]+ calcd for C27H32N3OSi 442.2309, found 442.2305.
2-(2-((Triisopropylsilyl)ethynyl)benzo[b]thiophen-3-yl)quinazolin-4(3H)-one (3y).
The product was obtained as yellow solid; Yield: 72 mg (78%). Rf: 0.6 (5:1 petroleum
ether/EtOAc) Mp: 170–171 °C; IR(neat) max: 2930, 2861, 2133, 1664, 1594, 1457, 885, 765,
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684, cm–1; 1H NMR (400 MHz, CDCl3) δ 10.49 (s, 1H), 9.00 (d, J = 7.9 Hz, 1H), 8.34 (d, J =
7.9 Hz, 1H), 7.88 (d, J = 8.1 Hz, 1H), 7.83–7.75 (m, 2H), 7.54–7.45 (m, 3H), 1.51–1.06 (m,
21H); 13C{1H} NMR (100 MHz, CDCl3) δ 161.2 (s), 149.0 (s), 147.4 (s), 139.2 (s), 136.7 (s),
134.6 (d), 130.1 (s), 128.2 (d), 127.2 (d), 126.8 (d), 126.6 (d), 126.6 (d), 125.9 (d), 124.8 (s),
121.7 (ds, 2C), 108.9 (s), 97.7 (s), 18.7 (q, 6C), 11.2 (d, 3C); HRMS (ESI–TOF) m/z: [M +
H]+ calcd for C27H31N2OSSi 459.1921, found 459.1916.
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(Z)-2-(1-Phenyl-4-(triisopropylsilyl)but-1-en-3-yn-2-yl)quinazolin-4(3H)-one (3z).
The product was obtained as yellow thick liquid; Yield: 62 mg (73%). Rf: 0.6 (5:1 petroleum
ether/EtOAc) IR(neat) max: 3308, 2941, 2864, 1689, 1587, 1462, 1234, 880, 769, 659, cm–1;
1H NMR (500 MHz, CDCl3) δ 11.33 (s, 1H), 8.30 (d, J = 7.9 Hz, 1H), 7.80 (d, J = 8.0 Hz,
2H), 7.79–7.71 (m, 2H), 7.52–7.42 (m, 4H), 7.12 (s, 1H), 1.46–1.09 (m, 21H); 13C{1H} NMR
(100 MHz, CDCl3) δ 161.0 (s), 150.2 (s), 149.2 (s), 136.9 (s), 134.6 (d), 129.9 (d), 129.0 (s),
128.8 (d, 2C), 127.8 (d), 127.4 (d), 127.24 (d), 126.9 (d, 2C), 126.7 (d), 121.8 (s), 109.5 (s),
102.9 (s), 18.7 (q, 6C), 11.2 (d, 3C); HRMS (ESI–TOF) m/z: [M + H]+ calcd for
C27H33N2OSi 429.2357, found 429.2356.
2-(2,6-Bis((triisopropylsilyl)ethynyl)phenyl)quinazolin-4(3H)-one (4a).
The product was obtained as white solid; Yield: 110 mg (94%). Rf: 0.7 (9:1 petroleum
ether/EtOAc) Mp. 188–189 °C; IR(neat) max: 2943, 2862, 2148, 1666, 1459, 1370, 1224,
880, 669 cm–1; 1H NMR (400 MHz, CDCl3) δ 9.00 (s, 1H), 8.28 (d, J = 7.9 Hz, 1H), 7.75 (dd,
J = 4.6, 1.2 Hz, 2H), 7.58–7.54 (m, 2H), 7.52–7.48 (m, 1H), 7.40 (dd, J = 8.3, 7.4 Hz, 1H),
0.86 (s, 42H); 13C{1H} NMR (100 MHz, CDCl3) δ 161.4 (s), 151.2 (s), 148.9 (s), 138.9 (s),
134.4 (d), 132.7 (d, 2C), 129.8 (d), 128.1 (d), 127.1 (d), 126.2 (d), 123.3 (s, 2C), 121.6 (s),
102.6 (s, 2C), 97.2 (s, 2C), 18.3 (q, 12C),11.0 (d, 6C); HRMS (ESI–TOF) m/z: [M + H]+
calcd for C36H51N2OSi2 583.3534, found 583.3543.
2-(4-Fluoro-2,6-bis((triisopropylsilyl)ethynyl)phenyl)quinazolin-4(3H)-one (4b).
The product was obtained as white solid; Yield: 100 mg (83%). Rf: 0.7 (9:1 petroleum
ether/EtOAc) Mp: 168–169 °C. IR(neat) max: 2942, 2863, 2149, 1668, 1464, 1369, 1223,
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7.88–7.65 (m, 2H), 7.52–7.48 (m, 1H), 7.26 (d, J = 8.6 Hz, 2H), 0.85 (s, 42H); 13C{1H} NMR
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(100 MHz, CDCl3) δ 162.4 (ds, JC-F = 251.7 Hz), 161.6 (s), 150.5 (s), 148.9 (s), 135.5 (ds,
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4JC-F = 3.4 Hz), 134.4 (d), 128.1 (d), 127.3 (d), 126.2 (d), 125.4 (ds, JC-F = 10.9 Hz, 2C),
121.6 (s), 119.7 (dd, 2JC-F = 23.3 Hz, 2C), 101.5 (ds, 4JC-F = 3.0 Hz, 2C), 98.7 (s, 2C), 18.3 (q,
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12C), 10.9 (d, 6C); HRMS (ESI–TOF) m/z: [M + H]+ calcd for C36H50FN2OSi2 601.3440,
found 601.3449.
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The product was obtained as white solid; Yield: 100 mg (81%). Rf: 0.7 (9:1 petroleum
ether/EtOAc) Mp: 185–186 °C; IR(neat) max: 2942, 2863, 2152, 1664, 1498, 1369, 1212,
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999, 772, 662 cm–1; H NMR (400 MHz, CDCl3) δ 9.10 (s, 1H), 8.27 (d, J = 7.7 Hz, 1H),
7.82–7.71 (m, 2H), 7.54 (s, 2H), 7.53–7.48 (m, 1H), 0.86 (s, 42H); 13C{1H} NMR (100 MHz,
CDCl3) δ 161.4 (s), 150.3 (s), 148.8 (s), 137.2 (s), 135.8 (s), 134.4 (d), 132.4 (d, 2C), 128.1
(d), 127.3 (d), 126.2 (d), 124.8 (s, 2C), 121.6 (s), 101.3 (s, 2C), 98.9 (s, 2C), 18.3 (q, 12 C),
10.9 (d, 6C); HRMS (ESI–TOF) m/z: [M + H]+ calcd for C36H50ClN2OSi2 617.3145, found
617.3153.
2-(4-Bromo-2,6-bis((triisopropylsilyl)ethynyl)phenyl)quinazolin-4(3H)-one (4d).
The product was obtained as white solid; Yield: 110 mg (83%). Rf: 0.7 (9:1 petroleum
ether/EtOAc) Mp: 181–182 °C; IR(neat) max: 2942, 2862, 2152, 1667, 1464, 1369, 1213,
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939, 773, 670 cm–1; H NMR (400 MHz, CDCl3) δ 9.09 (s, 1H), 8.27 (d, J = 7.8 Hz, 1H),
7.79–7.72 (m, 2H), 7.69 (s, 2H), 7.53–7.49 (m, 1H), 0.86 (s, 42H); 13C{1H} NMR (100 MHz,
CDCl3) δ 161.4 (s), 150.4 (s), 148.8 (s), 137.7 (s), 135.2 (d, 2C), 134.5 (d), 128.1(d), 127.3
(d), 126.2 (d), 124.9 (s, 2C), 123.6 (s), 121.6 (s), 101.2 (s, 2C), 99.1 (s, 2C), 18.3 (q, 12C),
10.9 (d, 6C); HRMS (ESI–TOF) m/z: [M + H]+ calcd for C36H50BrN2OSi2 661.2640, found
661.2643.
2-(4-Methyl-2,6-bis((triisopropylsilyl)ethynyl)phenyl)quinazolin-4(3H)-one (4e).
The product was obtained as white solid; Yield: 114 mg (96%). Rf: 0.7 (9:1 petroleum
ether/EtOAc) Mp: 190–191 °C. IR(neat) max: 2970, 2862, 2144, 1668, 1438, 1369, 1212,
901, 653 cm–1; 1H NMR (400 MHz, CDCl3) δ 8.98 (s, 1H), 8.27 (d, J = 7.8 Hz, 1H), 7.74 (d,
J = 3.8 Hz, 2H), 7.48 (m, 1H), 7.37 (s, 2H), 2.37 (s, 3H), 0.86 (s, 42H); 13C{1H} NMR (100
MHz, CDCl3) δ 161.8 (s), 151.2 (s), 148.9 (s), 140.1 (s), 136.2 (s), 134.3 (d), 133.3 (d, 2C),
128.1 (d), 127.0 (d), 126.1 (d), 123.0 (s, 2C), 121.6 (s), 102.8 (s, 2C), 96.5 (s, 2C), 20.93 (q),
18.3 (q, 12C), 10.9 (d, 6C); HRMS (ESI–TOF) m/z: [M + H]+ calcd for C37H53N2OSi2
597.3691, found 597.3702.
2-(4-Methoxy-2,6-bis((triisopropylsilyl)ethynyl)phenyl)quinazolin-4(3H)-one (4f).
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The product was obtained as white solid; Yield: 116 mg (95%). Rf: 0.8 (9:1 petroleum
ether/EtOAc) Mp: 183–184 °C; IR(neat) max: 2940, 2862, 2144, 1669, 1496, 1369, 1222,
880, 670 cm–1; 1H NMR (400 MHz, CDCl3) δ 9.09 (s, 1H), 8.27 (d, J = 7.9 Hz, 1H), 7.74 (dd,
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J = 4.6, 1.0 Hz, 2H), 7.54–7.40 (m, 1H), 7.05 (s, 2H), 3.86 (s, 3H), 0.86 (s, 42H); C{1H}
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NMR (100 MHz, CDCl3) δ 161.6 (s), 160.1 (s), 151.1 (s), 149.0 (s), 134.3 (d), 131.9 (s),
128.1 (d), 127.0 (d), 126.1 (d), 124.5 (s, 2C), 121.5 (s), 118.3 (d, 2C), 102.7 (s, 2C), 96.8 (s,
2C), 55.8 (q), 18.3 (q, 12C), 10.9 (d, 6C); HRMS (ESI–TOF) m/z: [M + H]+ calcd for
C37H53N2O2Si2 613.3640, found 613.3649.
2-(4-(Trifluoromethyl)-2,6-bis((triisopropylsilyl)ethynyl)phenyl)quinazolin-4(3H)-one
(4g).
The product was obtained as white solid; Yield: 114 mg (88%). Rf: 0.8 (9:1 petroleum
ether/EtOAc) Mp: 186–187 °C; IR(neat) max: 2942, 2860, 2156, 1670, 1496, 1373, 1232,
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950, 880, 674 cm–1; H NMR (400 MHz, CDCl3) δ 9.44 (s, 1H), 8.26 (d, J = 7.9 Hz, 1H),
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8.10–7.63 (m, 4H), 7.53–7.49 (m, 1H), 0.86 (s, 42H); C{1H} NMR (100 MHz, CDCl3) δ
161.5 (s), 150.1 (s), 148.8 (s), 141.7 (s), 134.5 (d), 132.5 (qs, 2JC-F = 33.3 Hz), 129.0 (qd, 3JC-
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= 3.6 Hz, 2C), 128.1 (d), 127.4 (d), 126.2 (d), 124.5 (s, 2C), 122.9 (qs, JC-F = 273.2 Hz),
F
121.7 (s), 101.2 (s, 2C), 99.6 (s, 2C), 18.3 (q, 12C), 10.9 (d, 6C); HRMS (ESI–TOF) m/z: [M
+ H]+ calcd for C37H50F3N2OSi2 651.3408, found 651.3420.
2-(3-Fluoro-2,6-bis((triisopropylsilyl)ethynyl)phenyl)quinazolin-4(3H)-one (4h).
The product was obtained as white solid; Yield: 91 mg (76%). Rf: 0.6 (9:1 petroleum
ether/EtOAc) Mp: 178–179 °C; IR(neat) max: 2933, 2861, 2140, 1667, 1463, 1370, 1226,
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881, 773, 674 cm–1; H NMR (400 MHz, CDCl3) δ 9.14 (s, 1H), 8.29 (d, J = 7.9 Hz, 1H),
7.81–7.68 (m, 2H), 7.56–7.48 (m, 2H), 7.18 (t, J = 8.5 Hz, 1H), 0.87 (d, 42H); 13C{1H} NMR
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(100 MHz, CDCl3) δ 163. 9 (ds, JC-F = 257.4 Hz), 161.4 (s), 149.9 (s), 148.8 (s), 140.6 (s),
134.5 (d), 134.1 (dd, 3JC-F = 8.4 Hz), 128.2 (d), 127.4 (d), 126.2 (d), 121.6 (s), 119.3 (ds, 4JC-F
= 4.0 Hz), 117.4 (dd, 2JC-F = 21.9 Hz), 112.7 (ds, 2JC-F = 18.49 Hz), 103.6 (s), 101.7 (s), 96.8
(s), 95.5 (s), 18.3 (dq, 4JC-F = 2.6 Hz, 12C), 11.0 (dd, 4JC-F = 4.6 Hz, 6C)19F NMR (376 MHz,
CDCl3) δ –105.4.; HRMS (ESI–TOF) m/z: [M + H]+ calcd for C36H50FN2OSi2 601.3440,
found 601.3452.
2-(3-Bromo-2,6-bis((triisopropylsilyl)ethynyl)phenyl)quinazolin-4(3H)-one (4i).
The product was obtained as white solid; Yield: 88 mg (67%). Rf: 0.7 (9:1 petroleum
ether/EtOAc) Mp: 184–185 °C; IR(neat) max: 2940, 2863, 2148, 1681, 1463, 1371, 1209,
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991, 879, 669 cm–1; H NMR (400 MHz, CDCl3) δ 9.12 (s, 1H), 8.27 (d, J = 7.5 Hz, 1H),
7.78–7.72 (m, 2H), 7.68 (d, J = 8.6 Hz, 1H), 7.51 (ddd, J = 8.2, 6.1, 2.2 Hz, 1H), 7.38 (d, J =
8.3 Hz, 1H), 0.91–0.74 (m, 42H); 13C{1H} NMR (100 MHz, CDCl3) δ 161.5 (s), 150.7 (s),
148.9 (s), 140.5 (s), 134.5 (d), 134.0 (d), 132.9 (d), 128.2 (d), 127.4 (d), 126.3 (d), 122.3 (s),
121.8 (s), 103.5 (s), 101.8 (s), 100.9 (s, 2C), 98.5 (s, 2C), 18.4 (q, 6C), 18.3 (q, 6C), 11.0 (d,
6C); HRMS (ESI–TOF) m/z: [M + H]+ calcd for C36H50BrN2OSi2 661.2640, found 661.2640.
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2-(3-Methoxy-2,6-bis((triisopropylsilyl)ethynyl)phenyl)quinazolin-4(3H)-one (4j).
The product was obtained as white solid; Yield: 86 mg (74%). Rf: 0.8 (9:1 petroleum
ether/EtOAc) Mp: 169–170 °C; IR(neat) max: 2942, 2863, 2133, 1669, 1496, 1370, 1232,
880, 670 cm–1; H NMR (400 MHz, CDCl3) δ 8.93 (s, 1H), 8.27 (d, J = 7.9 Hz, 1H), 7.76–
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7.73 (m, 2H), 7.61–7.35 (m, 2H), 6.94 (d, J = 8.7 Hz, 1H), 3.91 (s, 3H), 0.86 (s, 21H), 0.84
(s, 21H); 13C{1H} NMR (100 MHz, CDCl3) δ 161.4 (s), 160.9 (s), 151.0 (s), 149.0 (s), 140.4
(s), 134.3 (d), 134.0 (d), 128.1 (d), 127.1 (d), 126.1 (d), 121.6 (s), 115.1 (s), 113.1 (s), 112.3
(d), 102.6 (s), 101.8 (s), 98.5 (s), 94.6 (s), 56.4 (q), 18.4 (q, 12C), 10.9 (d, 6C); HRMS (ESI–
TOF) m/z: [M + H]+ calcd for C37H53N2O2Si2 613.3640, found 613.3640.
2-(2,6-Bis((triisopropylsilyl)ethynyl)phenyl)-7-methylquinazolin-4(3H)-one (4o).
The product was obtained as white solid; Yield: 102 mg (86%). Rf: 0.7 (9:1 petroleum
ether/EtOAc) Mp: 202–203 °C; IR(neat) max: 2941, 2862, 2141, 1657, 1453, 1370, 1224,
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985, 879, 667 cm–1; H NMR (500 MHz, CDCl3) δ 8.90 (s, 1H), 8.15 (d, J = 8.1 Hz, 1H),
7.61–7.55 (m, 3H), 7.39 (t, J = 7.8 Hz, 1H), 7.31 (d, J = 8.1 Hz, 1H), 2.49 (s, 3H), 0.87 (s,
42H); 13C{1H} NMR (125 MHz, CDCl3) δ 161.3 (s), 151.1 (s), 149.0 (s), 145.2 (s), 138.9 (s),
132.7 (d, 2C), 129.6 (d), 128.6 (d), 128.0 (d), 126.0 (d), 123.3 (s, 2C), 119.2 (s), 102.6 (s,
2C), 97.1 (s, 2C), 21.9 (q), 18.3 (q, 12C), 11.0 (d, 6C); HRMS (ESI–TOF) m/z: [M + H]+
calcd for C37H53N2OSi2 597.3691, found 597.3684.
2-(2,6-Bis((triisopropylsilyl)ethynyl)phenyl)-7-fluoroquinazolin-4(3H)-one (4p).
The product was obtained as white solid; Yield: 99 mg (83%). Rf: 0.7 (9:1 petroleum
ether/EtOAc) Mp: 203–204 °C; IR(neat) max: 2940, 2863, 2145, 1663, 1608, 1452, 1370,
1225, 985, 877, 667 cm–1; 1H NMR (400 MHz, CDCL3) δ 9.35 (s, 1H), 8.28 (dd, J = 8.7, 6.2
Hz, 1H), 7.56 (d, J = 7.8 Hz, 2H), 7.44–7.36 (m, 2H), 7.21 (td, J = 8.6, 2.3 Hz, 1H), 0.87 (s,
42H); C{1H} NMR (100 MHz, CDCl3) δ 166.5 (ds, JC–F = 254.3 Hz), 160.9 (s), 152.7 (s),
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151.2 (ds, JC-F = 13.1 Hz), 138.5 (s), 132.7 (d, 2C), 130.0 (d), 128.9 (dd, JC-F = 10.6 Hz),
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123.2 (s, 2C), 118.3 (s), 115.8 (dd, JC-F = 23.6 Hz), 113.4 (dd, JC-F = 22.1 Hz), 102.5 (s,
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2C), 97.4 (s, 2C), 18.3 (q, 12C), 10.9 (d, 6C); 19F NMR (376 MHz, CDCl3) δ –103.1.; HRMS
(ESI–TOF) m/z: [M + H]+ calcd for C36H50FN2OSi2 601.3440, found 601.3450.
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2-(2,6-Bis((triisopropylsilyl)ethynyl)phenyl)-7-bromoquinazolin-4(3H)-one (4q).
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The product was obtained as white solid; Yield: 106 mg (80%). Rf: 0.7 (9:1 petroleum
ether/EtOAc) Mp: 202–203 °C; IR(neat) max: 2941, 2862, 2145, 1661, 1596, 1445, 1370,
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1225, 986, 881, 670 cm–1; H NMR (400 MHz, CDCl3) δ 9.05 (s, 1H), 8.13 (d, J = 8.5 Hz,
1H), 7.93 (d, J = 1.8 Hz, 1H), 7.61 (dd, J = 8.5, 1.9 Hz, 1H), 7.57 (d, J = 7.9 Hz, 2H), 7.45–
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7.38 (m, 1H), 0.89 (s, 42H); C{1H} NMR (100 MHz, CDCl3) δ 160.8 (s), 152.5 (s), 149.9
(s), 138.4 (s), 132.8 (d, 2C), 130.9 (d), 130.5 (d), 130.0 (d), 129.0 (s), 127.6 (d), 123.2 (s,
2C), 120.5 (s), 102.4 (s, 2C), 97.5 (s, 2C), 18.4 (q, 12C), 10.9 (d, 6C); HRMS (ESI–TOF)
m/z: [M + H]+ calcd for C36H50BrN2OSi2 661.2640, found 661.2637.
2-(2,6-Bis((triisopropylsilyl)ethynyl)phenyl)-7-nitroquinazolin-4(3H)-one (4r).
The product was obtained as yellow solid; Yield: 98 mg (79%). Rf: 0.6 (9:1 petroleum
ether/EtOAc) Mp: 212–213 °C; IR(neat) max: 2941, 2862, 2155, 1667, 1606, 1534, 1453,
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1346, 1228, 985, 880, 668 cm–1; H NMR (400 MHz, CDCl3) δ 9.72 (brs, 1H), 8.59 (d, J =
1.8 Hz, 1H), 8.42 (d, J = 8.7 Hz, 1H), 8.26 (dd, J = 8.7, 2.0 Hz, 1H), 7.59 (d, J = 7.8 Hz, 2H),
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7.45 (t, J = 7.8 Hz, 1H), 0.86 (s, 42H); C{1H} NMR (100 MHz, CDCl3) δ 160.4 (s), 153.7
(s), 151.6 (s), 149.6 (s), 137.9 (s), 132.9 (d, 2C), 130.3 (d), 128.1 (d), 125.7 (s), 123.6 (d),
123.1 (s, 2C), 120.8 (d), 102.4 (s, 2C), 97.7 (s, 2C), 18.3 (q, 12C), 10.9 (d, 6C); HRMS (ESI–
TOF) m/z: [M + H]+ calcd for C36H50N3O3Si2 628.3385, found 628.3372.
2-(2,6-Bis((triisopropylsilyl)ethynyl)phenyl)-6,7-dimethoxyquinazolin-4(3H)-one (4s).
The product was obtained as white solid; Yield: 112 mg (87%). Rf: 0.7 (9:1 petroleum
ether/EtOAc) Mp: 193–194 °C; IR(neat) max: 2940, 2862, 2138, 1647, 1608, 1457, 1385,
1269, 1213, 1093, 980, 878, 666 cm–1; 1H NMR (400 MHz, CDCl3) δ 9.30 (s, 1H), 7.60 (s,
1H), 7.54 (d, J = 7.8 Hz, 2H), 7.38 (t, J = 7.8 Hz, 1H), 7.19 (s, 1H), 4.01 (s, 3H), 3.95 (s, 3H),
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0.88 (s, 42H); C{1H} NMR (100 MHz, CDCl3) δ 161.1 (s), 154.8 (s), 149.9 (s), 149.3 (s),
145.3 (s), 138.8 (s), 132.7 (d, 2C), 129.7 (d), 123.3 (s, 2C), 114.9 (s), 108.7 (d), 105.1 (d),
102.7 (s, 2C), 97.0 (s, 2C), 56.4 (q), 56.2 (q), 18.4 (q, 12C), 11.0 (d, 6C); HRMS (ESI–TOF)
m/z: [M]+ calcd for C38H54N2O3Si2 642.3667, found 642.3647.
2-(1,3-Bis((triisopropylsilyl)ethynyl)naphthalen-2-yl)quinazolin-4(3H)-one (4u).
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The product was obtained as white solid; Yield: 96 mg (76%). Rf: 0.7 (9:1 petroleum
ether/EtOAc) Mp: 204–205 °C; IR(neat) max: 2936, 2862, 2141, 1665, 1606, 1463, 1371,
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1023, 881, 665 cm–1; H NMR (400 MHz, CDCl3) δ 9.15 (s, 1H), 8.40 (d, J = 8.1 Hz, 1H),
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8.29 (d, J = 7.8 Hz, 1H), 8.10 (s, 1H), 7.85 (d, J = 7.8 Hz, 1H), 7.81–7.71 (m, 2H), 7.67–7.55
(m, 2H), 7.53–7.45 (m, 1H), 0.92 (s, 21H), 0.88 (s, 21H); 13C{1H} NMR (100 MHz, CDCl3) δ
161.5 (s), 151.6 (s), 149.0 (s), 136.6 (s), 134.3 (d), 133.3 (d), 133.0 (s), 132.6 (s), 128.6 (d),
128.3 (d), 128.2 (d), 128.1 (d), 127.1 (d), 126.8 (d), 126.2 (d), 121.7 (s), 121.7 (s), 119.4 (s),
103.1 (s), 100.7 (s), 96.4 (s, 2C), 18.4 (q, 6C), 18.3 (q, 6C), 11.0 (d, 6C); HRMS (ESI–TOF)
m/z: [M + H]+ calcd for C40H53N2OSi2 633.3691, found 633.3682.
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12-Methyleneisoindolo[1,2-b]quinazolin-10(12H)-one (5a): To a solution of TIPS-alkyne
3a (81 mg, 0.2 mmol) in THF (1 mL) was added TBAF (0.24 mL, 0.24 mmol) at 0 °C. After
addition, the solution was warmed up to room temperature and stirred for another 1h and
quenched with water, extracted with ethyl acetate (3×10 mL). The combined organic layers
were dried over Na2SO4. The volatile compounds were removed in vacuo and the residue was
subjected to column chromatography on silica gel to afford 5a (42 mg; 84%). Colorless solid;
Rf: 0.5 (5:1 petroleum ether/EtOAc); Mp: 280–282 °C; IR (neat) max: 2921, 2552, 1669,
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1650, 1602, 1468, 1334, 873, 768, 668 cm–1; H NMR (400 MHz, CDCl3) δ 8.44 (d, J = 7.8
Hz, 1H), 8.17 (d, J = 7.4 Hz, 1H), 7.90–7.76 (m, 3H), 7.63 (dt, J = 22.0, 7.3 Hz, 2H), 7.52 (t,
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J = 7.3 Hz, 1H), 7.07 (s, 1H), 5.94 (s, 1H); C{1H} NMR (100 MHz, CDCl3) δ 160.8 (s),
151.8 (s), 147.6 (s), 139.7 (s), 135.6 (s), 134.4 (d), 132.4 (d), 130.2 (d), 129.9 (s), 127.6 (d),
127.1 (d), 126.8 (d), 123.0 (d), 121.4 (s), 120.3 (d), 101.8 (t); HRMS (ESI-TOF) m/z: [M +
H]+ calcd for C16H11ON2 247.0866, found 247.0865.
8H-Isoquinolino[1,2-b]quinazolin-8-one (5b): To a solution of TIPS-alkyne 3a (81 mg, 0.2
mmol) in dry DMF (1.5 mL) was added NaH (60%) (4.8 mg, 0.2 mmol) at room temperature.
The solution was heated at 80 °C for 10h and then extracted with ethyl acetate. The combined
organic layers were dried over Na2SO4 and concentrated in vacuo. The residue was subjected
to column chromatography on silica gel to afford 5b (20 mg 41%). yellow solid; Rf: 0.7 (5:1
petroleum /EtOAc); Mp: 167–169 °C (168–170 °C)22; 1H NMR (400 MHz, CDCl3) δ 9.10 (d,
J = 8.0 Hz, 1H), 8.67 (d, J = 7.8 Hz, 1H), 8.48 (d, J = 7.9 Hz, 1H), 7.89 (dt, J = 15.0, 7.5 Hz,
2H), 7.77–7.72 (m, 1H), 7.67 (dd, J = 12.8, 7.5 Hz, 2H), 7.53 (t, J = 7.0 Hz, 1H), 7.05 (d, J =
13
7.8 Hz, 1H); C {1H} NMR (100 MHz, CDCl3) δ 159.5 (s), 147.6 (s), 146.2 (s), 134.8 (d),
132.9 (s), 132.2 (d, 2C), 128.5 (d), 127.6 (d), 127.3 (d), 127.3 (d), 126.5 (d), 125.8 (d), 122.0
(s), 117.8 (s), 113.2 (d); LC-MS (ESI) m/z: 247 [M+H] +.
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5-Bromo-6-(triisopropylsilyl)-8H-isoquinolino[1,2-b]quinazolin-8-one (5c): To a solution
of TIPS-alkyne 3a (81 mg, 0.2 mmol) in dioxane:water (1:1) (1.5 mL) was added NBS (53
mg, 0.3 mmol) at room temperature. The solution was heated at 80 °C for 10h and then
extracted with ethyl acetate. The combined organic layers were dried over Na2SO4 and
concentrated in vacuo. The residue was subjected to column chromatography on silica gel to
afford 5c (85 mg; 88%). yellow solid; Rf: 0.3 (5:1 petroleum /EtOAc); Mp: 180–182 °C; IR
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(neat) max: 2948, 2667, 1676, 1598, 1564, 1466, 1367, 879, 749, 665 cm–1; H NMR (500
MHz, CDCl3) δ 8.27 (d, J = 7.8 Hz, 1H), 8.18 (d, J = 7.5 Hz, 1H), 7.93 (d, J = 8.0 Hz, 1H),
7.74–7.62 (m, 2H), 7.57 (t, J = 7.5 Hz, 1H), 7.41 (t, J = 7.5 Hz, 1H), 7.32 (d, J = 8.4 Hz, 1H),
1.84–1.74 (m, 3H), 1.31 (brs, 18H); 13C {1H} NMR (100 MHz, CDCl3) δ 170.1 (s), 160.0 (s),
145.1 (s), 138.4 (s), 136.7 (s), 132.8 (d), 131.8 (d), 130.5 (s), 129.9 (d), 128.5 (d), 125.3 (d),
124.6 (d), 121.9 (d), 121.1 (d), 120.0 (s), 119.9 (s), 19.4 (q, 6C), 14.2 (d, 3C); HRMS (ESI-
81
TOF) m/z: [M + H]+ calcd for C25H30ON2 BrSi 483.1285, found 483.1292.
(E)-12-Benzylideneisoindolo[1,2-b]quinazolin-10(12H)-one (5d): In oven dried Schlenk
tube was charged with TIPS-alkyne 3a (81 mg, 0.2 mmol), aryl iodide (49 mg, 0.24 mmol),
PdCl2(PPh)3 (14 mg, 10 mol%), CuI (11.4 mg, 30 mol%) in sequence. The Schlenk tube was
vacuumed and backfilled with nitrogen for three times followed by adding anhydrous THF (1
ml). TBAF (0.4 mL, 1M in THF) was added into the solution at 0 °C and under the protection
of nitrogen through syringe and then the Schenk tube was closed tightly. After warming up to
room temperature and stirring for 1 h, water was added and the resulting mixture was
extracted with dichloromethane (2×20 mL). The combined organic layers were dried over
Na2SO4 and concentrated in vacuo. The residue was subjected to column chromatography on
silica gel to afford 5d (48 mg; 74%) as yellow solid.Rf: 0.7 (5:1 petroleum /EtOAc); Mp:
184−186 °C (184−185 °C)23; 1H NMR (500 MHz, CDCl3) δ 9.15 (s, 1 H) 8.48 (dd, J = 8.01,
1.14 Hz, 1 H) 8.20 (d, J = 7.63 Hz, 1 H) 7.83–7.88 (m, 1 H) 7.77–7.83 (m, 1 H) 7.49–7.56
(m, 4 H) 7.46–7.49 (m, 2H) 7.41–7.46 (m, 1H) 7.33–7.38 (m, 1 H) 7.27–7.30 (d, J= 8.0 Hz, 1
13
H); C {1H} NMR (125 MHz, CDCl3) δ 161.3 (s), 151.4 (s), 147.5 (s), 135.3 (s, 2C), 134.4
(s), 134.3 (d), 131.9 (d), 130.7 (s), 129.6 (d), 129.0 (d, 2C), 128.8 (d, 2C), 128.2 (d), 127.5
(d), 127.2 (d), 126.6 (d), 123.8 (d), 123.2 (d), 122.9 (d), 121.5 (s); HRMS (ESI-TOF) m/z: [M
+ H]+ calcd for C22H15N2O 323.1179, found 323.1179.
ASSOCIATED CONTENT
Supporting Information
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The Supporting Information is available free of charge on the ACS Publications website
http://pubs.acs.org. • 1H and 13C NMR spectra of all new compounds (PDF)
AUTHOR INFORMATION:
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Corresponding Author
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*E-mail: rajunipune@gmail.com, rs.rohokale@ncl.res.in
ORCID
Rajendra S. Rohokale: 0000-0001-8083-0466
Chepuri V. Ramana: 0000-0001-5801-311X
Notes
The authors declare no competing financial interest
ACKNOWLEDGMENT:
R. S. R. is thankful to the Science and Engineering Research Board (SERB), New Delhi for
the National Postdoctoral Fellowship (PDF/2016/001476) and R. G. K is thankful to the
CSIR, New Delhi for the award of a Senior Research Fellowship (SRF).
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