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Letters in Organic Chemistry, 2015, 12, 447-458 447

Metal-free Synthesis of 2,4,6-Trisubstituted Pyrimidines using
,-

Unsaturated Ketones and Benzamidine via Tandem Annulation-Oxidation
Pathway
Kamlesh S. Vadagaonkar,a Hanuman P. Kalmode,a Kaliyappan Murugan,b* and Atul C. Chaskara,c*

a
Department of Dyestuff Technology, Institute of Chemical Technology, Mumbai 400019, India;
b
National Taiwan University, Taipei 10617, Taiwan; cNational Centre for Nanosciences and
Nanotechnology, University of Mumbai, Mumbai-400098
Received May 12, 2014: Revised October 20, 2014: Accepted April 24, 2015

Abstract: A tandem metal-free synthesis of partly and fully substituted pyrimidines has been
accomplished from
,-unsaturated ketones and benzamidine in presence of triethyl amine. The
reaction proceeds via [3+3] annulation-oxidation sequence and the protocol has been found successful
for the synthesis of a wide range of pyrimidine derivatives.

Keywords: Benzamidine, Metal-free synthesis, Triethyl amine, Tandem [3+3] annulation-oxidation pathway,
,-Unsaturated
ketones.

INTRODUCTION stituted pyrimidines from -enaminones by cyclocondensa-

Substituted pyrimidines [1,2], an important class of aza- tion with carboxamides in the presence of a strong base.
heterocycles, are found in many natural products [3,4,5], However, these methods require an expensive metal catalyst,
bioactive molecules [6,7,8] and functional materials [9]. higher reaction temperature and starting materials that were
They are also widely used in drug discovery owing to their prepared by using multistep protocols. Thus, the develop-
presence in many established drugs such as voriconazole, ment of simpler, efficient and economically viable method-
avitriptan, crestor, gleevec, aggrenox, etc. [10,11]. Hence the ologies for the synthesis of pyrimidine derivatives is highly
development of economically and ecologically viable novel desired [25].
methodologies for the synthesis of substituted pyrimidines
,-Unsaturated ketones are easy to synthesize and have
has received the attention of the organic chemist community. been used to prepare various synthetic intermediates and
Amongst the numerous synthetic methodologies developed, heterocycles. To the best of our knowledge the use of these
the most common and well known synthetic approach in- substrates as precursors for the synthesis of pyrimidine de-
volves [3+3] annulation between N-C-N fragment such as rivatives using triethyl amine is hitherto unknown. In con-
amidines/guanidine and a C-C-C fragment exemplified by tinuation with our interest in development of straightforward
1,3-dicarbonyl compounds or their synthetic equivalents and simple synthetic protocol [26], we sought to develop a
[12,13,14]. C-C-N and C-N-C fragments also undergo [3+3] new method for the preparation of substituted pyrimidines.
annulation and offer pyrimidines [15]. The [4+2] annulations In this communication, we wish to report a highly efficient
[16,17,18] of C-C-N-C/ C-C-C-N with C-N or of C-N-C-N and metal-free protocol for the synthesis of substituted
with C-C and the [5+1] annulations [19,20] of N-C-C-C-N pyrimidines by the [3+3] annulation of various
,-
with C1 or C-N-C-C-C with N1 is also well documented. unsaturated ketones with benzamidine in the presence of
Recently, propargylic alcohols have been used as precursors triethyl amine in acetonitrile followed by oxidative aromati-
for the synthesis of pyrimidine derivatives (Scheme 1). zation with molecular oxygen.
Propargylic alcohols react with amidines in the presence of
transition metal catalysts such as Cu(OTf)2 and MnO2 in a
tandem approach [21,22] to give pyrimidines. Obera et al. RESULTS AND DISCUSSION
[23] reported an [2+2+2] intermolecular cycloaddition of Initially, the annulation reaction of 1,3-diphenyl-2-en-1-
alkynes with aryl nitriles in the presence of NbCl5 to form one 1a with benzamidine 2 was selected as a model reaction,
tetrasubstituted pyrimidine derivatives (Scheme 1). In addi- wherein the effect of different metal catalysts, bases, tem-
tion, Campagne et al. [24] disclosed the synthesis of disub- perature and solvents was studied. A 24% yield of 2,4,6-
triphenylpyrimidine 3a was obtained when 5 mol % of
*Address correspondence to these authors at the Department of Dyestuff Pd(OAc)2 was used alongwith triethyl amine in toluene at
Technology, Institute of Chemical Technology, Mumbai 400019, India and
National Centre for Nanosciences and Nanotechnology, University of 120 °C under oxygen atmosphere (Table 1, entry 1). When
Mumbai, Mumbai-400098, India; Tel: +91-22- 3361 1111/ 2707; Fax: +91- the temperature was reduced to 100 °C and 80 °C the yields
22- 3361 1020; E-mail: [email protected]
a obtained were 33% and 38%, respectively (Table 1, entries 2
These authors contributed equally to this work.

1875-6255/15 $58.00+.00 © 2015 Bentham Science Publishers

448 Letters in Organic Chemistry, 2015, Vol. 12, No. 7 Vadagaonkar et al.

Previous work: R1

OH NH Cu(II)/ Mn(IV)
N

R1 H2N Ph 120-150 oC
R2 N Ph
R2
R1

NbCl5 R2
R1 N
Ph N
120-150 oC
R2 Ph N Ph

Present work: R1
O NH R2
R2 TEA/CH3CN N
R1 H2N Ph 80 oC
R3 N Ph
R3

Scheme 1. Representative synthetic approaches of substituted pyrimidines.

Table 1. Optimization of reaction conditionsa.

O NH
Catalyst, Base N

H2N N
O2 (1.0 atm.),
5h

1a 2 3a

Entry Catalyst (mol%) Base (equiv.) Solvent Temp. °C Yield (%)c

1 Pd(OAc)2 (5) TEA (1.5) Toluene 120 24

2 Pd(OAc)2 (5) TEA (1.5) Toluene 100 33
3 Pd(OAc)2 (5) TEA (1.5) Toluene 80 38
4 Pd(OAc)2 (5) TEA (1.5) CH3CN 80 48
5 Pd(OAc)2 (5) TEA (1.5) CH3CN 80 37b
6 Cu(OAc)2 (10) TEA (1.5) CH3CN RT ---
7 Cu(OAc)2 (10) TEA (1.5) CH3CN 80 65
8 --------------- TEA (1.5) CH3CN RT ---
9 --------------- TEA (1.5) CH3CN 80 72
10 --------------- TEA (2.0) CH3CN 80 80
11 --------------- TEA (3.0) CH3CN 80 76
12 --------------- Na2CO3 (2.0) CH3CN 80 26
13 --------------- Cs2CO3 (2.0) CH3CN 80 19
14 --------------- DBU (2.0) CH3CN 80 35
15 --------------- TEA (2.0) DCE 80 29
16 --------------- TEA (2.0) DME 80 40
17 --------------- TEA (2.0) DMF 80 52
18 --------------- TEA (2.0) THF 80 43
19 --------------- --------------- CH3CN 80 ---
a
Reaction conditions: 1a (1.0 equiv.), 2 (1.0 equiv.), Catalyst (for entry 1-7, 5-10 mol %), Base (1.5-3.0 equiv.) in 10 mL of solvent for 5 h, O2 (1.0 atm.). bunder N2. cIsolated yields.
Metal
free Synthesis of 2,4,6-Trisubstituted Pyrimidines Letters in Organic Chemistry, 2015, Vol. 12, No. 7 449

and 3). Considering this relation between temperature and We next investigated the scope and limitations of this re-
yield, we carried out the reaction at 80 °C in acetonitrile and action by using different
,-unsaturated ketones (Table 2).
obtained 48% yield (Table 1, entry 4). When the same reac-
,-Unsaturated ketone 1b bearing no substituent on the
tion was conducted under nitrogen atmosphere a lower yield styryl portion afforded pyrimidine 3b in 75% yield. Chal-
(37%) was obtained (Table 1, entry 5) indicating that the cones (1c-1o) bearing a halogen group on the styryl portion
aromatization proceeded in the presence of atmospheric oxy- produced pyrimidine derivatives (3c-3o) respectively in good
gen. When Cu(OAc)2 was used as the catalyst (Table 1, en- to excellent yield (75-90%, Table 2, entries 3-15). Steric
tries 6 and 7), the reaction failed at room temperature but hindrance due to a halogen group near the double bond of
gave better yield at 80 °C. Similarly, the reaction also failed unsaturated ketones (1d, 1i, 1m) hampered the reaction and
in the absence of metal catalyst at room temperature (Table afforded low yields. We attempted the synthesis of tetrasub-
1, entry 8). To our surprise, 72% yield of the product was stituted pyrimidine (3p) from 3-acetyl coumarin (1p) under
obtained with 1.5 equiv. of triethyl amine in the absence of similar reaction conditions and observed that the reaction
metal catalyst (Table 1, entry 9). The use of 2.0 equiv. of took slightly longer time (8 h) and gave relatively low yield
triethyl amine was found to give the best yield (Table 1, en- (68%). The extended conjugation in -ionone adversely in-
try 10). When other bases such as Na2CO3, Cs2CO3 and DBU fluenced the reaction rate (14 h) and resulted in the forma-
were used, the yields obtained were lower (Table 1, entries tion of 3q in 52% yield. (E)-Pent-3-en-2-one (1r) and (E)-5-
12-14). The choice of solvent was found to be a key factor methylhex-3-en-2-one (1s) also underwent the annulation
(Table 1, entries 15-18). The best result was obtained in ace- reaction and afforded the corresponding pyrimidines (3r and
tonitrile. The reaction did not proceed in the absence of a 3s) in 55 and 63% yields, respectively.
base (Table 1, entry 19).

Table 2. Straightforward synthesis of pyrimidine derivativesa.

Entry Carbonyl Compound Pyrimidine Time (h) Yieldb (%)

1 N 5 80

N
1a

3a

CH3

2 6 75
N
CH3
1b N

3b

3 N 4 84
F
N
1c
F
3c
450 Letters in Organic Chemistry, 2015, Vol. 12, No. 7 Vadagaonkar et al.

Table 2. contd….

Entry Carbonyl Compound Pyrimidine Time (h) Yieldb (%)

N
4 5 78
Cl N

1d Cl

3d

N
5 5 85
Cl
N
1e
Cl
3e

N
6 4.5 86
Br
N
1f
Br
3f

Cl

7 N 5 87

N
1g Cl

3g

Cl

8 N 4 88
F
N
1h Cl
F
3h
Metal
free Synthesis of 2,4,6-Trisubstituted Pyrimidines Letters in Organic Chemistry, 2015, Vol. 12, No. 7 451

Table 2. contd….

Entry Carbonyl Compound Pyrimidine Time (h) Yieldb (%)

Cl

N
9 4.5 77
Cl N
1i Cl
Cl

3i
Cl

10 N 4 89
Cl
N
1j Cl
Cl
3j
Cl

11 N 4 90
Br
N
1k Cl
Br
3k
CH3

12 4.5 78
N
F CH3
1l N

F
3l

CH3

13 N 5 75
Cl CH3
N
1m
Cl

3m
452 Letters in Organic Chemistry, 2015, Vol. 12, No. 7 Vadagaonkar et al.

Table 2. contd….

Entry Carbonyl Compound Pyrimidine Time (h) Yieldb (%)

CH3

14 4.5 79
N
Cl CH3
1n N

Cl
3n

CH3

15 4.5 80
N
Br CH3
1o N

Br
3o

CH3
N N
16 8 68
O O
CH3

1p
O O

3p

H3C CH3 O

CH3 CH3 N N
17 H3C 14 52
CH3
CH3
1q CH3

3q

CH3
O

N
CH3
18 9 55
H3C N
H3C

1r
3r
Metal
free Synthesis of 2,4,6-Trisubstituted Pyrimidines Letters in Organic Chemistry, 2015, Vol. 12, No. 7 453

Table 2. contd….

Entry Carbonyl Compound Pyrimidine Time (h) Yieldb (%)

O CH3

CH3 N

19 H3C H3C 10 63
N
CH3 CH3

1s 3s

a
Reaction conditions: chalcone (1.0 mmol), benzamidine (1.0 mmol), triethylamine (2.0 mmol), CH3CN (10 mL), 80 °C. bIsolated yields.

O R1
NH
R2 R2
R1 TEA (2.0 equiv.) N
H2N Ph
CH3CN, O2 (1 atm.), 80 oC
R3 1 2 R3 N Ph

H+

O
R2
R1
NH
O2
R3 NH
Ph
A

Protonation

HO R1 R1
O O
R2 H R2
R2 N N
R1 R1 NH2 R2 Base
NH -H2O
R1 N Ph R3 N Ph
R3 NH R3 N H H
Ph
Ph
B B' C D

Scheme 2. Plausible mechanism.

which is in equilibrium with its tautomer B'. An 1,2-

A tentative mechanism for the pyrimidine ring formation
intramolecular addition produces cyclic tertiary alcohol C
is proposed in Scheme 2. Initially, conjugate addition of
that undergoes dehydration to produce dihydropyrimidine D.
benzamidine to the
,-unsaturated ketone forms intermedi-
D get aromatized in presence of molecular oxygen to form
ate A (enolate), which on protonation generates an imine B
substituted pyrimidine.
454 Letters in Organic Chemistry, 2015, Vol. 12, No. 7 Vadagaonkar et al.

EXPERIMENTAL SECTION 138.32, 141.23, 164.49, 164.67, 164.74; HRMS (ESI-MS):

m/z [M + H] + calcd for C23H19N2: 323.1548; found:
Materials and Equipment
323.1559.
Chemical reagents were obtained from commercial com-
panies. All reactions were done in a round bottom flask and 4-(4-Fluorophenyl)-2,6-diphenylpyrimidine (3c) [27c]
monitored by TLC performed on aluminium plates (0.25
White solid; yield 1.58 g; mp 168-170 °C; 1H NMR (400
mm, E. Merck) precoated with silica gel (Merck 60 F-254).
MHz, CDCl3):  = 7.22-7.27 (m, 2H), 7.55 (d, J = 7.6 Hz,
Developed TLC plates were visualized under a short-
6H), 7.96 (s, 1H), 8.28-8.32 (m, 4H), 8.71 (d, J = 5.6 Hz,
wavelength UV lamp. Reactions were conducted under N 2
2H); 13C NMR (100 MHz, CDCl3):  = 109.96, 115.91,
and O2 atmosphere in anhydrous solvents such as toluene,
acetonitrile, DCE, DME, THF and DMF. Yields refer to 116.12, 127.34, 128.52, 128.55, 129.01, 129.33, 129.42,
130.80, 130.93, 133.70, 137.49, 138.08, 163.41, 163.69,
spectroscopically (1H, 13C NMR) homogeneous material
164.58, 164.92, 165.91; HRMS (ESI-MS): m/z [M + H] +
obtained after column chromatography, which was per-
calcd for C22H16FN2: 327.1297; found: 327.1303.
formed on silica gel (100-200 mesh size) supplied by S. D.
Fine Chemicals Limited, India. 1H and 13C NMR were re-
4-(2-Chlorophenyl)-2,6-diphenylpyrimidine (3d)
corded in CDCl3 and DMSO-d6 solution with a Bruker 400
and 300 MHz spectrometers. Chemical shifts () are reported White solid; yield 1.47 g; mp 120-122 °C; 1H NMR (400
relative to SiMe4 ( = 0.0) as an internal standard. The num- MHz, CDCl3):  = 7.45-7.55 (m, 9H), 7.85 (d, J = 5.6 Hz,
ber of protons (n) for a given resonance is indicated by nH. 1H), 8.03 (s, 1H), 8.28 (d, J = 4.4 Hz, 2H), 8.67 (d, J = 4.4
Signal multiplicities are designated by the following abbre- Hz, 2H); 13C NMR (100 MHz, CDCl3):  = 115.24, 127.31,
viations: s, singlet; d, doublet; t, triplet; q, quartet; m, mul- 127.45, 128.55, 129.02, 130.57, 130.75, 130.78, 130.97,
tiplet; dd, doublet of doublet; J, coupling constant in Hz. 131.77, 132.50, 137.33, 137.63, 138.01, 163.95, 164.70,
High-resolution mass spectra were obtained by using posi- 164.76; HRMS (ESI-MS): m/z [M + H] + calcd for
tive electrospray ionization (ESI) by Time of Flight (TOF) C22H16ClN2: 343.1002; found: 343.1005.
method.
4-(4-Chlorophenyl)-2,6-diphenylpyrimidine (3e) [25a]
General Procedure for the Synthesis of Pyrimidine White solid; yield 1.61 g; mp 166-168 °C; 1H NMR (400
Derivatives MHz, CDCl3):  = 7.51-7.55 (m, 8H), 7.95 (s, 1H), 8.22-8.28
(m, 4H), 8.71 (d, J = 5.2 Hz, 2H); 13C NMR (100 MHz,
A round bottom flask was charged with the substituted CDCl3):  = 110.01, 127.35, 128.53, 128.56, 128.62, 129.02,
chalcone 1 (1.0 mmol), benzamidine 2 (1.0 mmol), triethy- 129.21, 130.84, 130.98, 135.99, 137.04, 137.40, 138.02,
lamine (2.0 mmol) and acetonitrile (10 mL). The mixture 163.53, 164.61, 165.00; HRMS (ESI-MS): m/z [M + H] +
was heated to 80 °C for 4-14 h, and then cooled to r.t. calcd for C22H16ClN2: 343.1002; found: 343.1009.
Evaporation of the solvent gave a crude reaction mixture, to
which water (10 mL) was added and the resulting mixture 4-(4-Bromophenyl)-2,6-diphenylpyrimidine (3f) [27d]
was extracted with EtOAc (3  20 mL). The combined or-
White solid; yield 1.63 g; mp 168-170 °C; 1H NMR (400
ganic layer was washed with 1N HCl (20 mL), brine and
MHz, CDCl3):  = 7.54-7.55 (m, 6H), 7.68 (d, J = 8.4 Hz,
dried over anhydrous Na2SO4. The solvent was concentrated
2H), 7.94 (s, 1H), 8.15 (d, J = 8.4 Hz, 2H), 8.27 (t, J = 4.0,
under reduced pressure and residue obtained was purified by
3.2 Hz, 2H), 8.70 (t, J = 5.2, 2.0 Hz, 2H); 13C NMR (100
silica gel column chromatography (100-200 mesh) using n- MHz, CDCl3):  = 109.98, 125.49, 127.36, 128.53, 128.56,
hexane:Et2O (95:05) as the eluent to afford the correspond- 128.85, 129.02, 130.85, 130.99, 132.17, 136.44, 137.38,
ing pyrimidine 3. 138.00, 163.60, 164.62, 165.02; HRMS (ESI-MS): m/z [M +
H]+ calcd for C22H16BrN2: 387.0497; found: 387.0504.
Product Characterization
4-(3-Chlorophenyl)-2,6-diphenylpyrimidine (3g) [27e]
2,4,6-Triphenylpyrimidine (3a) [27a] White solid; yield 1.64 g; mp 146-148 °C; 1H NMR (400
White solid; yield 1.50 g; mp 184-186 °C; H NMR (4001 MHz, CDCl3):  = 7.47-7.56 (m, 8H), 7.97 (s, 1H), 8.15 (d, J
MHz, CDCl3):  = 7.56 (s, 9H), 8.02 (s, 1H), 8.30 (s, 4H), = 6.4 Hz, 1H), 8.29 (s, 3H), 8.72 (d, J = 6.0 Hz, 2H); 13C
8.75 (s, 2H); 13C NMR (100 MHz, CDCl3):  = 110.38, NMR (100 MHz, CDCl3):  = 110.34, 125.41, 127.38,
127.37, 128.54, 129.00, 130.72, 130.86, 137.61, 138.22, 127.49, 128.56, 128.58, 129.04, 130.23, 130.78, 130.89,
164.57, 164.82; HRMS (ESI-MS): m/z [M + H]+ calcd for 131.04, 135.16, 137.32, 137.93, 139.43, 163.38, 164.69,
C22H17N2: 309.1391; found: 309.1398. 165.12; HRMS (ESI-MS): m/z [M + H] + calcd for
C22H16ClN2: 343.1002; found: 343.1005.
2,4-Diphenyl-6-(p-tolyl)pyrimidine (3b) [27b]
4-(3-Chlorophenyl)-6-(4-fluorophenyl)-2-phenylpyrimidine
White solid; yield 1.41 g; mp 150-152 °C; 1H NMR (400 (3h)
MHz, CDCl3):  = 2.46 (s, 3H), 7.37 (d, J = 8.0 Hz, 2H),
7.55 (m, 6H), 7.99 (s, 1H), 8.21 (d, J = 8.0 Hz, 2H), 8.29 (d, White solid; yield 1.67 g; mp 166-168 °C; 1H NMR (400
J = 6.4 Hz, 2H), 8.74 (d, J = 6.8 Hz, 2H); 13C NMR (100 MHz, CDCl3):  = 7.22-7.26 (m, 2H), 7.49-7.55 (m, 5H),
MHz, CDCl3):  = 21.58, 110.02, 127.26, 127.35, 128.51, 7.91 (s, 1H), 8.13 (d, J = 6.8 Hz, 1H), 8.27-8.31 (m, 3H),
128.54, 128.97, 129.72, 130.65, 130.77, 134.78, 137.72, 8.69 (t, J = 4.8, 2.8 Hz, 2H); 13C NMR (100 MHz, CDCl3): 
Metal
free Synthesis of 2,4,6-Trisubstituted Pyrimidines Letters in Organic Chemistry, 2015, Vol. 12, No. 7 455

= 109.92, 115.97, 116.18, 125.40, 127.47, 128.53, 128.59, 132.50, 134.52, 137.73, 138.12, 141.37, 163.90, 164.61;
129.37, 129.46, 130.25, 130.86, 130.97, 133.44, 135.18, HRMS (ESI-MS): m/z [M + H]+ calcd for C23H18ClN2:
137.79, 139.30, 163.47, 163.97, 164.69, 166.01; HRMS 357.1158; found: 357.1152.
(ESI-MS): m/z [M + H]+ calcd for C22H15ClFN2: 361.0908;
found: 361.0917. 4-(4-Chlorophenyl)-2-phenyl-6-(p-tolyl)pyrimidine (3n)
White solid; yield 1.50 g; mp 166-168 °C; 1H NMR (400
4-(2-Chlorophenyl)-6-(3-chlorophenyl)-2-phenylpyrimidine MHz, CDCl3):
= 2.46 (s, 3H), 7.36 (d, J = 8.0 Hz, 2H),
(3i) 7.53 (m, 5H), 7.93 (s, 1H), 8.20 (dd, J = 8.4, 8.0 Hz, 4H),
White solid; yield 1.46 g; mp 142-144 °C; 1H NMR (400 8.70 (d, J = 6.0 Hz, 2H); 13C NMR (100 MHz, CDCl3):
=
MHz, CDCl3):
= 7.44-7.54 (m, 8H), 7.85 (t, J = 6.0, 2.4 21.58, 109.66, 127.25, 128.51, 128.53, 128.61, 129.18,
Hz, 1H), 7.99 (s, 1H), 8.12 (d, J = 6.8 Hz, 1H), 8.29 (s, 1H), 129.74, 130.76, 134.58, 136.10, 136.94, 138.12, 141.38,
8.66 (d, J = 4.0 Hz, 2H); 13C NMR (100 MHz, CDCl3):
= 163.40, 164.54, 164.92; HRMS (ESI-MS): m/z [M + H] +
115.26, 125.50, 127.36, 127.58, 128.56, 128.62, 130.27, calcd for C23H18ClN2: 357.1158; found: 357.1159.
130.61, 130.91, 130.97, 131.77, 132.48, 135.22, 137.38,
137.72, 139.16, 162.52, 164.83, 165.09; HRMS (ESI-MS): 4-(4-Bromophenyl)-2-phenyl-6-(p-tolyl)pyrimidine (3o)
m/z [M + H]+ calcd for C22H15Cl2N2: 377.0612; found: White solid; yield 1.52 g; mp 174-176 °C; 1H NMR (400
377.0621. MHz, CDCl3):
= 2.46 (s, 3H), 7.36 (d, J = 8.0 Hz, 2H),
7.54 (m, 3H), 7.68 (d, J = 8.4 Hz, 2H), 7.93 (s, 1H), 8.17 (m,
4-(3-Chlorophenyl)-6-(4-chlorophenyl)-2-phenylpyrimidine 4H), 8.70 (t, J = 5.6, 2.0 Hz, 2H); 13C NMR (100 MHz,
(3j) CDCl3):
= 21.59, 109.62, 125.38, 127.25, 128.52, 128.84,
White solid; yield 1.69 g; mp 140-142 °C; 1H NMR (400 129.74, 130.77, 132.14, 134.56, 136.56, 138.10, 141.39,
163.46, 164.55, 164.94; HRMS (ESI-MS): m/z [M + H] +
MHz, CDCl3):
= 7.50-7.53 (m, 7H), 7.87 (s, 1H), 8.10-8.24
calcd for C23H18BrN2: 401.0653; found: 401.0652.
(m, 4H), 8.67 (s, 2H); 13C NMR (100 MHz, CDCl3):
=
109.93, 125.39, 127.45, 128.53, 128.61, 129.24, 130.23,
4-Methyl-2-phenyl-5H-chromeno[4,3-d]pyrimidin-5-one
130.90, 131.01, 135.18, 135.67, 137.25, 137.71, 139.18, (3p)
163.51, 163.79, 164.69; HRMS (ESI-MS): m/z [M + H] +
calcd for C22H15Cl2N2: 377.0612; found: 377.0623. Yellow solid; yield 1.27 g; mp 254-256 °C; 1H NMR
(300 MHz, DMSO-d6):
= 2.30 (s, 3H), 6.67 (t, J = 7.2 Hz,
4-(4-Bromophenyl)-6-(3-chlorophenyl)-2-phenylpyrimidine 1H), 6.80 (d, J = 7.8 Hz, 1H), 6.91-7.03 (m, 2H), 7.49-7.59
(3k) (m, 3H), 8.08 (d, J = 6.9 Hz, 2H); 13C NMR (75 MHz,
DMSO-d6):
= 24.73, 115.34, 119.09, 120.72, 125.44,
White solid; yield 1.72 g; mp 130-132 °C; 1H NMR (400 127.08, 127.64, 128.66, 128.82, 131.44, 132.41, 153.88,
MHz, CDCl3):
= 7.49-7.55 (m, 5H), 7.68 (d, J = 8.4 Hz, 155.14, 164.18; HRMS (ESI-MS): m/z [M + H]+ calcd for
2H), 7.91 (s, 1H), 8.12-8.16 (m, 3H), 8.26 (s, 1H), 8.68 (t, J C18H13N2O2: 289.0977; found: 289.0991.
= 4.4, 3.2 Hz, 2H); 13C NMR (100 MHz, CDCl3):
=
109.97, 125.41, 125.72, 127.48, 128.54, 128.61, 128.86, 4-Methyl-2-phenyl-6-(2,6,6-trimethylcyclohex-1-en-1-
130.26, 130.92, 131.03, 132.24, 135.20, 136.17, 137.71, yl)pyrimidine (3q)
139.21, 163.62, 163.94, 164.77; HRMS (ESI-MS): m/z [M +
White solid; yield 0.97 g; mp 74-76 °C; 1H NMR (300
H]+ calcd for C22H15BrClN2: 421.0107; found: 421.0104. MHz, CDCl3):
= 1.08 (s, 6H), 1.43 (s, 3H), 1.57-1.61 (m,
2H), 1.74-1.83 (m, 2H), 2.09 (t, J = 6.6 Hz, 2H), 2.58 (s,
4-(4-Fluorophenyl)-2-phenyl-6-(p-tolyl)pyrimidine (3l) 3H), 6.83 (d, J = 0.3 Hz, 1H), 7.44-7.49 (m, 3H), 8.44-8.50
White solid; yield 1.47 g; mp 150-152 °C; 1H NMR (400 (m, 2H); 13C NMR (75 MHz, CDCl3):
= 19.27, 21.29,
MHz, CDCl3):
= 2.46 (s, 3H), 7.24 (distorted t, J = 8.4 Hz, 24.45, 28.93, 32.00, 34.41, 39.47, 120.18, 128.47, 128.49,
2H), 7.36 (d, J = 7.6 Hz, 2H), 7.54 (m, 3H), 7.92 (s, 1H), 128.75, 129.00, 130.30, 131.21, 138.50, 139.28, 163.98,
8.19 (d, J = 7.6 Hz, 2H), 8.27-8.31 (distorted q, J = 6.0, 1.6 166.10, 168.79; HRMS (ESI-MS): m/z [M + H]+ calcd for
Hz, 2H), 8.71 (d, J = 6.0 Hz, 2H); 13C NMR (100 MHz, C20H25N2: 293.2017; found: 293.2068.
CDCl3):
= 21.57, 109.58, 115.86, 116.08, 127.24, 128.51,
129.30, 129.39, 129.73, 130.72, 133.79, 134.65, 138.18, 4,6-Dimethyl-2-phenylpyrimidine (3r) [27f]
141.32, 163.37, 163.53, 164.48, 164.81, 165.86; HRMS White solid; yield 0.99 g; mp 82-84 °C; 1H NMR (400
(ESI-MS): m/z [M + H]+ calcd for C23H18FN2: 341.1454; MHz, CDCl3):
= 2.51 (s, 6H), 6.89 (s, 1H), 7.42-7.47
found: 341.1458. (m, 3H), 8.40-8.43 (m, 2H); 13C NMR (100 MHz, CDCl3):

= 24.06, 117.85, 128.12, 128.34, 130.16, 138.05, 164.08,
4-(2-Chlorophenyl)-2-phenyl-6-(p-tolyl)pyrimidine (3m) 166.64; HRMS (ESI-MS): m/z [M + H]+ calcd for C12H13N2:
185.1079; found: 185.1093.
White solid; yield 1.42 g; mp 124-126 °C; 1H NMR (400
MHz, CDCl3):
= 2.46 (s, 3H), 7.36 (d, J = 7.6 Hz, 2H),
4-Isopropyl-6-methyl-2-phenylpyrimidine (3s)
7.43-7.56 (m, 6H), 7.85 (t, J = 6.8, 2.0 Hz, 1H), 7.99 (s, 1H),
8.19 (d, J = 8.0 Hz, 2H), 8.68 (t, J = 5.2, 1.6 Hz, 2H); 13C White solid; yield 1.15 g; mp 102-104 °C; 1H NMR (400
NMR (100 MHz, CDCl3):
= 21.59, 114.89, 127.29, MHz, CDCl3):
= 1.33 (d, J = 6.8 Hz, 6H), 2.54 (s, 3H),
127.36, 128.53, 129.76, 130.56, 130.68, 130.71, 131.76, 2.96-3.03 (m, 1H), 6.90 (s, 1H), 7.45 (m, 3H), 8.46 (d, J =
456 Letters in Organic Chemistry, 2015, Vol. 12, No. 7 Vadagaonkar et al.

7.2 Hz, 2H); 13C NMR (100 MHz, CDCl3):
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C14H17N2: 213.1392; found: 213.1398. S. H.; Reep, B.; McDonald, O. B.; Wood, E. R.; Rusnak, D. W.;
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benzamidine. The protocol is simple, facile and practical. analogs as potent, highly selective, and orally bioavailable NHE-1
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of D-A type molecules for optoelectronic applications is cur- Synthesis and biological evaluation of new quinazoline and
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New Delhi, respectively for award of Senior Research Fel- [6] Nagourney, R. A.; Fox, P.; Schein, P. S. A comparison of the
lowships. The authors thank Prof. P. M. Bhate for help in biological and biochemical properties of 1-(4-Amino-2-
methylpyrimidin-5-yl)methyl-3-(2-chloroethyl)-3-nitrosourea and
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Web site along with the published article. Stefano, F.; Urban, F.; Shuttleworth, S. J.; Saghir, N.; Sheldrake,
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