Swift and efficient synthesis of 4-phenylquinazolines: Involvement of N-heterocyclic carbene in the key cyclization step

Article abstract of DOI:10.1021/jo902726k

"Chemical Equation Presented" An original route to 2-alkyamino-4-phenylquinazolines in three steps from simple (hetero)aromatic amines is reported here. The key step involves the intramolecular cyclization of benzoyl arylguanidines performed in [OMIm]Cl ionic liquid. The basic (hetero)aromatic guanidines deprotonate the imidazolium-based ionic liquid, thus triggering the cascade process ultimately leading to the intramolecular cyclization. This reaction is the first example of a Friedel-Crafts-type reaction in which an N-heterocyclic carbene is involved in the formation of the electrophilic intermediate.

Full text of DOI:10.1021/jo902726k

pubs.acs.org/joc
antitubercular,4 antibacterial,5 antimalarial,6 and antitumor
Swift and Efficient Synthesis of
4-Phenylquinazolines: Involvement of
N-Heterocyclic Carbene in the Key Cyclization Step
properties.7 Quinazolines also display promising activities
against neurological disorders.8 The growing importance of
these heterocycles in therapeutics as well as the development
of green chemistry encourage the search for environmentally
benign synthetic methods for their preparation.9
†
Julien Debray, Jean-Marc Leveque, Christian Philouze,
‡
†
ꢀ ^
Micheline Draye,‡ and Martine Demeunynck*,†
We recently described10 the synthesis of 2-alkylaminoqui-
nazolin-4-one analogues by Friedel-Crafts cyclization of ethoxy-
carbonyl-protected guanidino(hetero)cycles in the presence
of Lewis acid catalyst (halosilanes/DMF or AlCl3/toluene)
(Scheme 1).
†
ꢀ
Departement Chimie Moleculaire, UMR 5250 & FR 2607,
CNRS/Universite de Grenoble, BP 53, 38041 Grenoble Cedex
ꢀ
ꢀ
‡
ꢀ
9, France, and Laboratoire de Chimie Moleculaire
et Environnement-Universite de Savoie-Polytech,
ꢀ
Savoie-73376 Le Bourget du Lac Cedex, France
SCHEME 1. Synthesis of 2-Alkylaminoquinazolin-4-ones
martine.demeunynck@ujf-grenoble.fr
Received January 4, 2010
To increase the scope of this reaction and in an effort
to prepare 2-amino-4-phenylquinazolines, we turned our
attention to the reactivity of the N-benzoyl-protected analo-
gues. We report here a process based on the microwave-
assisted cyclization of N-alkyl-N0-(hetero)arylbenzoylgu-
anidines, emphasizing the essential and unexpected role
played by the ionic liquid in the key Friedel-Crafts-type
reaction.
To test the ability of the benzoyl arylguanidines to under-
go intramolecular Friedel-Crafts reaction, the guanidino-
quinoline 2a, prepared in two steps from 6-aminoquinoline
1, was treated with POCl3 in a Vilsmeier-Haack-type pro-
cedure. The cyclization proceeded well, and the desired
quinazolinone 3a was isolated in reasonable yield (60%).
The polycyclic structure of 3a was confirmed by X-ray crys-
tallography.
An original route to 2-alkyamino-4-phenylquinazolines
in three steps from simple (hetero)aromatic amines is
reported here. The key step involves the intramolecular
cyclization of benzoyl arylguanidines performed in
[OMIm]Cl ionic liquid. The basic (hetero)aromatic gua-
nidines deprotonate the imidazolium-based ionic liquid,
thus triggering the cascade process ultimately leading to
the intramolecular cyclization. This reaction is the first
example of a Friedel-Crafts-type reaction in which an
N-heterocyclic carbene is involved in the formation of the
electrophilic intermediate.
To avoid the use of toxic reactants, we then looked for a
greener procedure. Combination of Lewis acid and ionic liquids
(5) Beylin, V.; Boyles, D. C.; Curran, T. T.; Macikenas, D.; Parlett, R. V.;
Vrieze, D. Org. Proc. Res. Dev. 2007, 11, 441.
(6) Guan, J.; Zhang, Q.; O’Neil, M.; Obaldia, N. III; Ager, A.; Gerena, L.;
Lin, A. J. Antimicrob. Agents Chemother. 2005, 49, 4928.
(7) (a) Bavetsias, V.; Clauss, R.; Henderson, E. A. Org. Biomol. Chem.
2003, 1, 1943. (b) Bavetsias, V.; Henderson, E. A.; McDonald, E. Tetrahe-
ꢀ
dron 2007, 63, 1537. (c) Guillonneau, C.; Nault, A.; Raimbaud, E.; Leonce,
S.; Kraus-Berthier, L.; Pierre, A.; Goldstein, S. Bioorg. Med. Chem. 2005, 13,
ꢀ
175. (d) Srivastava, V.; Srivastava, A. M.; Tiwari, A. K.; Srivastava, R.;
Sharma, R.; Sharma, H.; Singh, V. K. Chem. Biol. Drug Design 2009, 74, 297.
(8) (a) Laddha, S. S.; Bhatnagar, S. P. Bioorg. Med. Chem. 2009, 17, 6796.
(b) Wang, H.-H.; Chou, C.-J.; Liao, J.-F.; Chen, C. F. Eur. J. Pharmacol.
2001, 413, 221. (c) Decker, M. Eur. J. Med. Chem. 2005, 40, 305.
(9) (a) Potewar, T. M.; Nadaf, R. N.; Daniel, T.; Lahoti, R. J.; Srinivasan,
K. V. Synth. Commun. 2005, 35, 231. (b) Khosropour, A. R.; Mohammadpoor-
Baltork, I.; Ghorbankhani, H. Tetrahedron Lett. 2006, 47, 3561. (c) Heravi,
M. M.; Ranjbar, L.; Derikvand, F.; Alimadadi, B.; Oskooie, H. A.; Bamoharram,
F. F. Mol. Diversity 2008, 12, 181. (d) Kidwai, M.; Saxena, S.; Mohan, R.
J. Heterocycl. Chem. 2005, 42, 703. (e) Connolly, T. J.; McGarry, P.; Sukhtankar,
S. Green Chem. 2005, 7, 586. (f) Mehta, S.; Swarnkar, N.; Vyas, M.; Vardia, J.;
Punjabi, P. B.; Ameta, S. C. Bull. Korean Chem. Soc. 2007, 28, 2338. (g) Kaur, B.;
Kaur, R. ARKIVOC 2007, 315. (h) Ghozlan, S. A. S.; Mohamed, M. H.;
Abdelmoniem, A. M.; Abdelhamid, I. A. ARKIVOC 2009, 302. (i) Kabri, Y.;
Gellis, A.; Vanelle, P. Green Chem. 2009, 11, 201.
Our group is interested in the design of original nitrogen
heterocycles and, among them, quinazoline fused polycycles.
Quinazoline derivatives constitute an important class of com-
pounds, from natural or synthetic sources,1 that exhibit remar-
kable activities, including anti-inflammatory,2 antihypertensive3
(1) Michael, J. P. Nat. Prod. Rep. 2008, 25, 166.
(2) Alafeefy, A. M.; Kadi, A. A.; El-Azab, A.; Abdel-Hamide, S. G.;
Daba, M.-H. Y. Arch. Pharm. Chem. Life Sci. 2008, 341, 377.
(3) Alagarsamy, V.; Pathak, U. S. Bioorg. Med. Chem. 2007, 15, 3457.
(4) Raghavendra, N. M.; Thampi, P.; Gurubasavarajaswamy, P. M.;
Sriram, D. Arch. Pharm. Chem. Life Sci. 2007, 340, 635.
(10) Zeghida, W.; Debray, J.; Chierici, S.; Dumy, P.; Demeunynck, M.
J. Org. Chem. 2008, 73, 2473.
2092 J. Org. Chem. 2010, 75, 2092–2095
Published on Web 02/19/2010
DOI: 10.1021/jo902726k
r
2010 American Chemical Society

Debray et al.
JOCNote
SCHEME 2. Cyclization of Benzoylguanidines 2a-d
TABLE 1. Synthesis of 2-Piperidinyl-4-phenylquinazolines
has been reported to achieve Friedel-Crafts reactions.11 We
therefore chose to investigate the reactivity of benzoylguani-
dines in the imidazolium-based ionic liquid [OMIm]Cl under
microwave irradiation. The ionic liquid is commercially avail-
able, but it can be easily prepared on a large scale by alkylation
of methyl imidazole with octyl chloride.
As imidazolium-based ionic liquids are known to be non-
innocent solvents, a solution of benzoylguanidines 2a in
[OMIm]Cl was first irradiated (10 min, 110 °C) in the absence
of any acid or basic catalyst. To our great satisfaction and
surprise, 2a was quantitatively (as indicated by HPLC
analysis) transformed into the desired tricyclic derivatives
3a (Scheme 2). The reaction also occurred under traditional
heating (110 °C), but it required a longer time to completion
(1 h compared to 10 min under microwave irradiation). The
reaction was then performed with arylbenzoylguanidines
containing various amino substituents. The cyclization pro-
ceeded well with secondary (propylamine) or tertiary amines
(piperidine, morpholine, or pyrrolidine). The lower yield
(65%) observed for the propylamine-containing quinazoline
3a was due to less efficient purification steps. One limitation
of the methodology is the access to quinazolines containing
aromatic amines at position 2 (NR1R2 =ArNH). Indeed, in
these cases, the presence of two competing aromatic rings on
the guanidine generates a mixture of compounds as the cycli-
zation may occur on the two rings.
To assess its scope, the reaction was performed using
benzoylguanidines containing various aromatic and hetero-
aromatic rings. As shown in Table 1, the cyclization occurred
in good to excellent yields on phenyl and both electron-rich
and electron-deficient heterocycles. As indicated in lines 3
and 4, the reaction was regioselective.
This unexpected cyclization under relatively mild condi-
tions prompted us to study the mechanism of reaction and, in
particular, the possible role of the ionic liquid in the process.
When the ionic liquid was replaced by N-methylpyrrolidi-
none as a solvent, no reaction occurred, even at higher tem-
perature (220 °C, 10 min irradiation). Imidazolium-based
ionic liquids are prone to form the corresponding highly
reactive N-heterocyclic carbenes in the presence of strong
bases.12 To check the possible involvement of carbenes in
the process, we replaced the 1,3-disubstituted imidazolium
[OMIm]Cl with the 1,2,3-trisubstituted analogue [OMMIm]Cl.
The reaction was performed using the indan derivative 5(Table 1,
entry 2). The solution of 5 in [OMMIm]Cl was submitted to
microwave irradiation (110 °C, up to 30 min), and no reac-
tion was observed, the starting guanidine 5 being recovered.
Exchanging the chloride counterion by the less nucleophilic
tetrafluoroborate ion in either [OMIm]X or [OMMIm]X ionic
liquids does not modify the course of the reaction, indicating
that the counterion was not involved in the mechanism.
From these experiments, we therefore propose the mecha-
nism depicted in Scheme 3. The first step involves the [OMIm]
H-2 abstraction by the basic arylguanidine, with formation of
the corresponding carbene and the acylguanidinium species I.
Addition of the carbene to the hydroxyimino tautomer (I0),
assisted by the presence of the positive charge on the guanidine
nitrogens, gives the highly electrophilic intermediate II that
undergoes the Friedel-Crafts-type cyclization. Elimination of
imidazolium and water yields the pyrimidine ring.
(11) (a) Bahrami, K.; Khodei, M. M.; Shahbazi, F. Tetrahedron Lett.
2008, 49, 3931. (b) Khodaei, M. M.; Bahrami, K.; Shahbazi, F. Chem. Lett.
2008, 37, 844. (c) Liu, Z. C.; Meng, X. H.; Zhang, R.; Xu, C. M. Petroleum
Sci. Technol. 2009, 27, 226.
(12) (a) Sohn, S. S.; Rosen, E. L.; Bode, J. W. J. Am. Chem. Soc. 2004, 126,
14370. (b) Chan, A.; Scheidt, K. A. J. Am. Chem. Soc. 2006, 128, 4558.
(c) Burstein, C.; Glorius, F. Angew. Chem., Int. Ed. 2004, 43, 6205.
(d) Aggarwal, V.; Emme, I.; Mereu, A. Chem. Commun. 2002, 1612. (e) Estager,
Other experiments also support this hypothesis. In situ
formation of the guanidinium cation, by addition of 1 equiv
of hydrochloric acid to the solution of 5 in [OMMIm]Cl,
prevents the cyclization step, thus indicating that the pre-
sence of the positive charge conjugated to the CO (species I/I0
^
J.; Leveque, J.-M.; Turgis, R.; Draye, M. J. Mol. Catal. A: Chemical 2006, 256,
261. (f) Xu, L.-W.; Gao, Y.; Yin, J.-J.; Li, L.; Xia, C.-G. Tetrahedron Lett.
2005, 46.
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Debray et al.
JOCNote
SCHEME 3. Proposed Reaction Pathway
the process ultimately leading to the intramolecular cycliza-
tion. This methodology is original in two aspects: the reacting
molecule itself induces the carbene formation, and therefore
triggers the events leading to the final cylization, and second, it
is, to the best of our knowledge, the first example of aromatic
electrophilic substitution in which a carbene is involved to form
the electrophilic reagent.14
Experimental Section
Microwave reactions were conducted using a CEM Discover
Synthesis Unit (CEM Corp., Matthews, NC) equipped with a
continuous focused microwave power delivery system with
selectable power output from 0 to 300 W. The reaction was
performed in glass vessels (capacity 10 mL) sealed with a
septum. The temperature of the reaction mixture was monitored
using a calibrated infrared temperature control mounted under
the reaction vessel. All experiments were conducted under
magnetic stirring (rotating magnetic plate located under the
microwave cavity and using Teflon-coated magnetic stir bar in
the vessel). The typical experiment was irradiated in a sealed
tube at 110 °C for 10 min (ramp time 30 s, Tmax=110 °C, power
max=200 W).
General Procedure for the Synthesis of Guanidine Derivatives.
Benzoyl isothiocyanate (135 μL, 1.2 mmol) was added to a
solution of the (hetero)cyclic amine (1 mmol) in CH2Cl2 (10 mL).
The solution was stirred at room temperature for 1 h. The
disappearance of the starting amine was checked by TLC or HPLC
analysis. To the solution were successively added Et3N (416 μL,
3 mmol), amines (2 mmol), and EDCI (229 mg, 1.2 mmol). The
resulting mixture was stirred for 6 h at room temperature or 60 °C
(depending on the solubility of the intermediate thiourea). The
solvent was then evaporated to dryness. The resulting oily residue
was then diluted with water. The guanidine was filtered, washed
with water, and dried under vacuum at 50 °C . The purity of the
guanidine was checked by HPLC analysis and was found to be
>95%. The guanidines 2a-d and 4-7 were characterized by 1H
and 13C NMR and HRMS. The data are given as Supporting
Information.
General Procedure for the Synthesis of Quinazoline Deriva-
tives. The protected guanidine (1 mmol) was solubilized in
[OMIm]Cl (2 mL), and the solution was stirred at 110 °C during
10 min under microwave irradiation (CEM Discover). The
reaction was monitored by HPLC or TLC. When the reaction
was completed, the hot solution was poured into water, and
aqueous NH4OH was added dropwise to reach pH 9-10. The
solid was filtered and washed several times with water. If nece-
ssary, the crude quinazolines were purified by column chroma-
tography (SiO2) dichloromethane/methanol 99/1).
in Scheme 2) is not sufficient to activate the CdO bond
toward the aromatic electrophilic substitution. Addition of
1 equiv of hydrochloric acid to the solution of 5 in [OMIm]Cl
also inhibits the cyclization process, confirming the crucial
role of the guanidine as a base. The acidity of the ionic liquid,
[OMIm]Cl, is not sufficient to catalyze the reaction, as the
cyclization is not observed when the reaction was performed
in the 2-methyl-substituted analogue [OMMIm]Cl, which
displays similar acidic properties.13 Moreover, increasing the
acidity of the solvent by addition of HCl has definitely a
negative effect as shown above. To evidence a possible cata-
lytic effect, we performed the cyclization reation in dichloro-
ethane using 0.5 equiv of [OMIm]Cl. The cyclization pro-
ceeded, but due to higher dilution, we only observed 70%
transformation after 1 h of irradiation at 110 °C.
In summary, we have designed an original, efficient, and
sustainable route to highly substituted aromatic and hetero-
aromatic fused 2-alkyamino-4-phenylquinazolines in three
steps from simple (hetero)aromatic amines. The key step
involves an intramolecular Friedel-Crafts-type cyclization
under mild conditions. The reaction is performed in the
easily accessible [OMIm]X ionic liquid, which plays the dual
roles of an excellent solvent of polar molecules particularly
suitable for using microwave technology and a key reagent
by generating N-heterocyclic carbenes. The cyclization may
be performed using traditional heating, but the use of micro-
wave irradiation shortens the reaction time (10 min instead
of 1 h).
4-Phenyl-2-propylaminopyrido[3,2-f]quinazoline (3a): yield
62%; mp 185-186 °C; 1H NMR (300 MHz, DMSO-d6) δ 8.65
(d, 1H, J=4 Hz), 8.11 (d, 1H, J=9 Hz), 7.75 (d, 1H, J=9 Hz),
7.58-7.51 (m, 5H), 7.15 (m, 1H), 3.89 (m, 4H), 1.64-1.58
(m, 6H); HRMS calcd for C20H19N4 (Mþ) 315.1604, found
315.1596.
Unlike what has been reported so far in the literature,
there is no need of strongly basic catalyst for the carbene
generation. Indeed, the intrinsic basicity of the reacting
molecules, (hetero)aromatic guanidines, is sufficient to de-
protonate the imidazolium-based ionic liquid, thus initiating
4-Phenyl-2-(piperidin-1-yl)-pyrido[3,2-f]quinazoline (3b): yield
81%; mp 181-182 °C; 1H NMR (300 MHz, DMSO-d6) δ
8.65-8.64 (m, 1H), 8.11 (d, 1H, J = 9 Hz), 7.75 (d, 1H, J =
9 Hz), 7.58-7.51 (m, 5H), 7.15 (m, 1H), 3.89 (m, 4H), 1.64-1.58
(m, 6H); 13C NMR (75 MHz, DMSO-d6): δ 167.3, 157.9, 154.9,
147.9, 146.0, 141.1, 136.4, 132.5, 129.9, 129.5, 129.1, 128.3,
124.9, 120.8, 111.5, 44.2, 25.4, 24.3; HRMS calcd for C22H21-
N4 (Mþ) 341.1760, found 341.1751.
(13) Indeed the characteristic source of reactivity of the imidazolium
cation is the high acidity of its C2-H position (pKa=21-24), whose abstrac-
tion results in a highly stabilized N-heterocyclic carbene; see: (a) Thomazeau, C.;
Olivier-Bourbigou, H.; Magna, L.; Luts, S.; Gilbert, B. J. Am. Chem. Soc. 2003,
125, 5264. (b) Amyes, T. L.; Diver, S. T.; Richard, J. P.; Rivas, F. M.; Toth, K.
J. Am. Chem. Soc. 2004, 126, 4366. (c) Sowmiah, S.; Srinivasadesikan, V.; Tseng,
M.-C.; Chu, Y.-H. Molecules 2009, 14, 3780.
(14) N-Heterocyclic carbene palladium(II) complexes have been used as
catalysts for various reactions included Friedel-Crafts-type processes; see:
Liu, Z; Shi, M. Tetrahydron: Asymmetry 2009, 20, 119. Liu, Z.; Zhang, T.;
Shi, M. Organometallics 2008, 27, 2668.
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Debray et al.
JOCNote
2-Morpholino-4-phenylpyrido[3,2-f]quinazoline (3c): yield 81%;
mp181-182 °C;1H NMR (300 MHz, DMSO-d6) δ 8.69-8.68(m,
1H), 8.15 (d, 1H, J=9 Hz), 7.78 (d, 1H, J=9 Hz), 7.59-7.50 (m,
5H), 7.20-7.15 (m, 1H), 3.87 (t, 4H), 3.70 (t, 4H); 13C NMR (75
MHz, DMSO-d6) δ 168.1, 158.7, 155.5, 148.9, 146.9, 141.6, 137.4,
133.4, 130.5, 130.3, 129.8, 129.0, 125.5, 121.7, 112.9, 66.7, 44.6;
HRMS calcd for C21H19N4O (Mþ) 343.1553, found 343.1546.
4-Phenyl-2-(pyrrolidin-1-yl)-pyrido[3,2-f]quinazoline (3d): yield
81%; mp 205-206 °C; 1H NMR (400 MHz, DMSO-d6) δ
8.70-8.68 (m, 1H), 8.15 (d, 1H, J = 9 Hz), 7.83 (d, 1H, J =
9 Hz), 7.59-7.51 (m, 5H), 7.22-7.19 (m, 1H), 3.66 (m, 4H), 1.99
(m, 4H); 13C NMR (75 MHz, DMSO-d6) δ 168.1, 157.7, 155.6,
148.4, 146.0, 141.9, 136.9, 133.5, 130.8, 130.3, 129.9, 129.0, 125.8,
121.7, 112.2, 47.2, 25.7; HRMS calcd for C21H19N4 (Mþ) 327.1604,
found 327.1595.
140.4, 130.2, 129.6, 129.5, 128.6, 128.5, 124.2, 123.0, 118.8,
106.3, 103.4, 44.8, 25.8, 24.9; HRMS calcd for C21H21N4 (Mþ)
329.1760, found 329.1750.
5,7-Dimethyl-2-(piperidyl-1-yl)pyrazolo[4,3-e]pyrimidine (11):
yield 92%; mp 105-106 °C ; 1H NMR (300 MHz, DMSO-d6) δ
7.72-7.68 (m, 2H), 7.55-7.53 (m, 3H), 3.88-3.76 (m, 4H),
1.64-1.54 (m, 6H); 13C NMR (75 MHz, DMSO-d6) δ 162.6,
159.4, 156.4, 140.4, 137.6, 129.9, 128.9, 128.2, 103.9, 44.6, 32.4,
25.3, 24.3, 15.2; HRMS calcd for C18H22N5 (Mþ) 308.1869,
found 308.1859.
X-ray Crystallography. Crystal data for C20H18N4: Mr,
314.39 g mol-1; crystal dimensions (mm), 0.30 ꢀ 0.26 ꢀ 0.10;
3
crystal system, triclinic; space group, P-1; unit cell dimensions
˚
˚
˚
and volume, a = 8.770(6) A, b =10.038(4) A, c = 10.810(5) A,
3
˚
R =107.39(4)°, β =102.58(7)°, γ =108.01(4)°, V = 812(1) A ,
no. of formula units in the unit cell Z = 2; calculated density
6-Methyl-4-phenyl-2-(piperidin-1-yl)quinazoline (8): yield 76%;
1
mp 104-106 °C; H NMR (300 MHz, DMSO-d6) δ 7.70-7.74
r
calcd, 1.286 g/cm3; linear absorption coefficient, m 0.617 mm-1
;
˚
(m, 2H), 7.50-7.58 (m, 6H), 3.97-4.02 (m, 4H), 2.38 (s, 3H),
1.72-1.77 (m, 6H); 13C NMR (75 MHz, DMSO-d6) δ 19.3, 25.2;
26.0, 44.4, 117.0, 118.3, 120.4, 122.7, 123.4, 125.2, 127.9, 130.0,
135.3, 145.3, 157.7, 166.3; HRMS calcd for C20H22N3 (Mþ)
304.1808, found 304.1797.
radiation and wavelength, l Cu KR=1.54178 A; temperature of
measurement, 293.0 K, 2 Qmax 150°; no. of measured and
independent reflections, 3397 and 3215; Rint, 0.04; R [I >
2.0σ(I)] = 0.0649, wR = 0.0775, GoF = 1.98, refined on F;
residual electron density, 0.32. The data collection was scaned
in ω mode on a Bruker AXS-Enraf-Nonius CAD4 diffracto-
meter.
4-Phenyl-2-(piperidin-1-yl)cyclopenta[g]quinazoline (9): yield
72%; mp 122-123 °C °C; 1H NMR (300 MHz, CDCl3) δ
7.67-7.64 (m, 2H), 7.55 (d, 1H, J = 8.4 Hz), 7.43-7.42 (m,
3H), 6.95 (d, 1H, J = 8.4 Hz), 3.91-3.90 (m, 4H), 3.17 (t, 2H),
2.97 (t, 2H), 2.13 (q, 2H), 1.60-1.58 (m, 6H); 13C NMR (75 MHz,
CDCl3) δ 168.9, 158.6, 150.7, 149.5, 138.7, 138.3, 129.9, 129.3,
128.1, 126.0, 118.9, 116.1, 44.9, 34.3, 30.3, 25.9, 25.0, 24.7; HRMS
calcd for C22H23N3 (Mþ) 330.1964, found 330.1953.
Acknowledgment. Financial support has been provided
ꢀ
^
by Region Rhone-Alpes (cluster chimie). J.D. is the recipi-
ent of a fellowship from the Departement de Chimie
ꢀ
Moleculaire.
4-Phenyl-2-(piperidin-1-yl)-5H-pyrrolo[2,3-f]quinazoline (10):
yield 73%; mp 175-177 °C; 1H NMR (300 MHz, DMSO-d6) δ
8.96 (s, 1H), 7.92 (d, 1H, J=8.7 Hz), 7.62 (m, 5H), 7,23 (d, 1H,
J=8.7 Hz), 7.03 (m, 1H), 6.49 (m, 1H), 3.84 (m, 4H), 1.61-1.56
(m, 6H); 13C NMR (75 MHz, DMSO-d6) δ 164.6, 157.5, 152.4,
Supporting Information Available: Experimental proce-
dures and spectral data for all new compounds, including
crystallographic data for compounds 3a. This material is avail-
able free of charge via the Internet at http://pubs.acs.org.
J. Org. Chem. Vol. 75, No. 6, 2010 2095