An efficient synthesis of 3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one derivatives via an iminophosphorane

Article abstract of DOI:10.1002/jhet.1825

The iminophosphorane (3), obtained from reaction of ethyl 3-amino-4-cyano-1-phenyl-1H-pyrrole-2-carboxylate (2) with triphenylphosphine, hexachloroethane, and triethylamine, reacted with aromatic isocyanates to give carbodiimides (4). Further reaction of

Full text of DOI:10.1002/jhet.1825

Month 2014
An Efficient Synthesis of 3H-Pyrrolo[3,2-d]pyrimidin-4(5H)-one
Derivatives via an Iminophosphorane
a
a
Ping He,a,b Yan-Mei Yan, and Ming-Wu Ding
*
aKey Laboratory of Pesticide & Chemical Biology of Ministry of Education, Central China Normal University,
Wuhan, 430079, People’s Republic of China
bCollege of Chemical Engineering and Food Science, Hubei University of Arts and Science, Xiangyang
441053, People’s Republic of China
*
E-mail: ding5229@yahoo.com.cn
Received May 28, 2012
DOI 10.1002/jhet.1825
Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com).
The iminophosphorane (3), obtained from reaction of ethyl 3-amino-4-cyano-1-phenyl-1H-pyrrole-2-
carboxylate (2) with triphenylphosphine, hexachloroethane, and triethylamine, reacted with aromatic
isocyanates to give carbodiimides (4). Further reaction of 4 with various amines, phenols, or ROH to give
2,3,5,7-tetrasubstituted 3H-pyrrolo[3,2-d]pyrimidine-4(5H)-ones (6) in satisfactory yields in the presence
of catalytic amount of sodium alkoxide or solid potassium carbonate.
J. Heterocyclic Chem., 00, 00 (2014).
INTRODUCTION
iminophosphorane (3) by treatment with triphenyl phosphine,
hexachloroethane, and triethylamine in dry acetonitrile
(Scheme 1).
Pyrrolo[3,2-d]pyrimidines (also called 9-deazapurines)
have been reported to exhibit widespread biological activities
and have been used as potent A1- and A2- adenosine receptor
antagonists [1], purine nucleoside phosphorylase inhibitors
[2–5]. Some derivatives of this ring system have also shown
good anticancer activity [6,7]. Many methods have been
reported for the synthesis of pyrrolo[3,2-d]pyrimidines.
One of the generally used approach involved elaboration of
a pyrrole ring onto the preformed pyrimidine bearing reactive
functionalities at C-4 and C-5 [8–11]; another used strategy
involvedthe formation of a pyrimidine ring onto the 3-amino-
pyrrole intermediate [12–14]. Although some 3H-pyrrolo
[3,2-d]pyrimidine-4(5H)-ones have been constructed via
3-amino-2-carboxylpyrroles, which seems to be a very useful
method, but the synthesis of 2,3,5,7-tetrasubstituted 3H-pyr-
rolo[3,2-d]pyrimidine-4(5H)-ones are rarely described.
On the other hand, aza-Wittig reactions have received
increased attention because of their utility in the synthesis
of nitrogen-containing heterocyclic compounds [15–20].
Recently, we have been interested in the synthesis of
fused pyrimidinones via aza-Wittig reaction, with the aim
of evaluating their fungicidal activities [21–26]. Herein, we
wish to report a new facile and efficient synthesis of
2,3,5,7-tetrasubstituted 3H-pyrrolo[3,2-d]pyrimidine-4(5H)-
ones via aza-Wittig reaction, starting from easily accessible
ethyl 3-amino-4-cyano-1-phenyl-1H-pyrrole-2-carboxylate.
The iminophosphorane (3) was allowed to react with
aromatic isocyanates to yield carbodiimides (4), which were
further treated with amines to provide guanidine intermediates
(5). In the presence of EtONa/EtOH, 5 were easily converted
to 2-amino-3H-pyrrolo[3,2-d]pyrimidine-4(5H)-one deriva-
tives (6) (Y = NR1R2) at RT in satisfactory yields (Scheme 2).
The results are listed in Table 1 (entry 6a–6j). The cyclization
reactions were achieved all in moderate to good yields
whatever the amine that used was cyclic or acyclic ones. It
is noteworthy that the product 6 contain a carbonitrile group,
which is very important in design of biologically active
heterocycles.
The structure of 3H-pyrrolo[3,2-d]pyrimidine-4(5H)-ones
(6) was confirmedbytheir spectrumdata. For example, the IR
spectra of 6arevealed CNandC═O absorption bands at 2214
1
and 1709cmꢀ1, respectively. The H-NMR spectrum of
6a shows two triplets at 3.16 and 3.43 ppm because of the
NCH2 and OCH2, respectively. The signals attributable
to the Ar—Hs and 6-H of the pyrrole ring are found at
7.30–7.47 and 7.63 ppm as mutiplet and singlet, respectively.
The MS spectrum of 6a shows molecular ion peak at m/z 397
with 53% abundance.
To expand the method of preparation of 3H-pyrrolo[3,2-d]
pyrimidine-4(5H)-ones, alcohols and phenols were further
used to react with carbodiimides (4). When alcohols were
added to the solution of carbodiimides (4), catalytic amount
of RONa was necessary for the reaction to occur to give
2-alkoxy-3H-pyrrolo[3,2-d]pyrimidine-4(5H)-ones derivatives
(6) (Y = OR). When carbodiimides (4) reacted with phenols,
the presence of catalytic amount of potassium carbonate can
RESULTS AND DISCUSSION
The ethyl 3-amino-4-cyano-1-phenyl-1H-pyrrole-2-carbox-
ylate (2), easily obtained by reaction of compound 1 with ethyl
2-bromoacetate in the basic condition [27], was converted to
© 2014 HeteroCorporation

P. He, Y.-M. Yan, and M.-W. Ding
Vol 000
Scheme 1
absorption in reciprocal centimeter. Elementary analyses were taken
on a Vario Elementary III elementary analysis instrument (Elementar
Company, Hanau, Germany).
Procedure for the preparation of compound 2. Compound
2 was obtained from the reaction of malononitrile with aniline and
ethyl orthoformate in the presence of K2CO3, followed by reacting
with ethyl 2-bromoacetate according to a literature report. White
crystals (yield: 75%); mp: 150–151ꢁC (Lit. [27] mp: 153–154ꢁC).
Ethyl-3-triphenylphosphoranylideneamino-4-cyano-1-phenyl-
1H-pyrrole-2-carboxylate (3). To a mixture of ethyl 3-amino-4-
cyano-1-phenyl-1H-pyrrole-2-carboxylate (2) (2.04 g, 8 mmol),
PPh3 (3.14 g, 12 mmol), and C2Cl6 (2.84 g, 12 mmol) in dry
CH3CN (40mL) was added dropwise NEt3 (2.42 g, 24mmol) at
RT. After stirred at 25ꢁC for 4 h, the solvent was removed under
reduced pressure, and the residue was recrystallized from EtOH
to give iminophosphorane (3) as white crystals, 3.91g (95%), mp
Scheme 2
1
122–123ꢁC; H-NMR (CDCl3): d 0.89 (t, J = 7.2 Hz, 3H, CH3),
3.82 (q, J = 7.2 Hz, 2H, CH2), 7.02 (s, 1H, C═C—H), 7.15–7.84
(m, 20H, Ar—H); MS: m/z (%) 515 (3, M+), 501 (48), 458 (29),
430 (100), 388 (55), 374 (99), 360 (61), 345 (65), 320 (45), 264
(47), 251 (47), 180 (38), 125 (27), 77 (47). Anal. Calcd for
C32H26N3O2P: C, 74.55; H, 5.08; N, 8.15; Found: C, 74.60; H,
5.11; N, 8.09.
General preparation of 2-amino-3H-pyrrolo[3,2-d]pyrimidine-
4(5H)-one (6a–6j).
To a solution of iminophosphorane
(3) (1.55 g, 3 mmol) in dry methylene dichloride (15 mL), aromatic
isocyanate (3mmol) was added under nitrogen at RT. After
the reaction mixture was left to stand for 10–12h at 0–5ꢁC, the
solvent was removed under reduced pressure, and a mixture of
ether/petroleum ether (1:2, 20mL) was added to precipitate
triphenylphosphine oxide. After filtration, the solvent was removed
to give carbodiimide (4), which was used directly without further
purification. To the solution of 4 prepared earlier in methylene
dichloride (15 mL), amine (3mmol) was added. After the reaction
mixture was allowed to stand for 2–8 h, the solvent was removed,
and anhydrous ethanol (10–15mL) with several drops of EtONa
in EtOH was added. The mixture was stirred for 1–4 h at RT. The
solution was then concentrated under reduced pressure, and the
residual was recrystallized from methylene dichloride/ethanol to
give 2-amino-3H-pyrrolo[3,2-d]pyrimidine-4(5H)-one.
make the reaction took place to give 6 (Y = OAr0) directly in
good yields. The results are listed in Table 1 (entry 6k–6r).
It is reasonable to assume that both of the reactions of carbo-
diimides (4) with alcohols and phenols take place through an
original nucleophilic addition to give the intermediates 5,
which consequently cyclized to produce 3H-pyrrolo[3,2-d]
pyrimidine-4(5H)-ones (6) under the basic condition.
In conclusion, we have developed an efficient way to
prepare various 3H-pyrrolo[3,2-d]pyrimidine-4(5H)-one
derivatives via reaction of carbodiimides with a variety of
amines, alcohols, and phenols. Because of its mild reaction
conditions, good yields, and easily changing substituents, it
will serves as a new tool for preparing of many biologically
and pharmaceutically active 3H-pyrrolo[3,2-d]pyrimidine-4
(5H)-ones.
7-Cyano-3,5-diphenyl-2-(4-morpholino)-3H-pyrrolo[3,2-d]
pyrimidine-4(5H)-one (6a).
1H-NMR (CDCl3): d 3.16
(t, J = 4.6 Hz, 4H, 2NCH2), 3.43 (t, J = 4.6 Hz, 4H, 2OCH2),
7.30–7.47 (m, 10H, Ar—H), 7.63 (s, 1H, Ar—H); IR
(potassium bromide): 2214 (CN), 1709 (C═O), 1606, 1581,
1563, 1506, 1349, 1247 cmꢀ1; MS: m/z (%) 397 (53, M+), 352
(65), 340 (100), 311 (60), 264 (34), 209 (30), 180 (31), 154
(24), 103 (21), 77 (55).
7-Cyano-3,5-diphenyl-2-(pyrrolidin-1-yl)-3H-pyrrolo[3,2-
d]pyrimidine-4(5H)-one (6b). 1H-NMR (CDCl3): d 1.70–1.74
(m, 4H, 2CH2), 3.07 (t, J = 6.4 Hz, 4H, 2NCH2), 7.27–7.45
(m, 10H, Ar—H), 7.56 (s, 1H, Ar—H); IR (potassium
bromide): 2212 (CN), 1700 (C═O), 1608, 1586, 1564, 1500,
1429, 1230 cmꢀ1; MS: m/z (%) 381 (74, M+), 352 (40), 276
(32), 77 (100).
EXPERIMENTAL
Melting points were determined using a X-4 model apparatus
(Beijing Taike Company, Beijing, People’s Republic of China)
and were uncalibrated. MS were measured on a Finnigan Trace
MS spectrometer (Thermo Company, Palo Alto, CA). NMR spectra
were recorded in CDCl3 on a Varian Mercury Plus 400 (400MHz)
spectrometer (Varian Company, Palo Alto, CA), and chemical shifts
(d) were given in parts per million using (CH3)4Si as an internal
reference (d = 0). IR were recorded on a PE-983 IR spectrometer
(PerkinElmer Company, Waltham, MA) as KBr pellets with
7-Cyano-3,5-diphenyl-2-(piperidin-1-yl)-3H-pyrrolo[3,2-d]
pyrimidine-4(5H)-one (6c).
1H-NMR (CDCl3): d 1.20–1.43
(m, 6H, 3CH2), 3.12 (t, J = 5.6 Hz, 4H, 2NCH2), 7.28–7.45
(m, 10H, Ar—H), 7.60 (s, 1H, Ar—H); IR (potassium bromide):
2210 (CN), 1701 (C═O), 1605, 1577, 1569, 1504, 1241 cmꢀ1
;
MS: m/z (%) 395 (82, M+), 366 (56), 352 (29), 311 (37), 290 (34),
276 (46), 209 (33), 160 (100), 103 (52), 84 (82), 77 (62).
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
3H-Pyrrolo[3,2-d]pyrimidin-4(5H)-one Derivatives
Table 1
Physical and analytical data of compounds 6.
Analysis %
Calcd/found
H
Compd
Ar
Y
Time
hours
mp
Yield
Molecular
Formula
[a]
(ꢁC)
%
C
N
6a
6b
6c
6d
6e
6f
Ph
Ph
4-morpholinyl
1-pyrrolidinyl
1-piperidinyl
-NEt2
2
2
2
4
4
4
8
8
6
6
8
5
3
4
5
8
3
1
249–250
287–288
241–242
180–181
179–180
101–103
84–86
80
85
80
89
90
80
86
78
82
85
65
67
75
80
85
65
75
65
C
23H19N5O2
69.51
69.80
72.42
72.49
72.89
72.99
72.04
72.14
72.97
73.14
74.49
74.54
75.12
75.24
73.78
73.83
67.33
67.14
68.81
68.68
74.25
74.46
74.63
74.69
74.98
75.17
69.02
69.28
65.72
65.79
71.55
71.67
71.34
71.29
67.37
67.28
4.82
4.93
5.02
5.16
5.35
5.46
5.52
5.48
6.12
6.18
7.11
7.08
7.52
7.63
6.65
6.77
5.42
5.65
5.02
4.99
3.99
4.13
4.34
4.45
4.66
4.85
3.79
3.84
3.09
3.22
3.93
3.75
4.90
4.99
4.04
4.16
17.62
17.51
18.36
18.51
17.71
17.58
18.26
18.38
17.02
17.15
14.98
15.13
14.13
14.32
15.93
15.86
15.70
15.92
17.45
17.56
13.85
13.95
13.39
13.56
12.95
13.08
12.38
12.44
12.26
12.35
12.84
12.94
15.13
15.33
14.97
14.84
C23H19N5O
C24H21N5O
C23H21N5O
C25H25N5O
C29H33N5O
C31H37N5O
C27H29N5O
C25H24ClN5O
C23H20FN5O
C25H16N4O2
C26H18N4O2
C27H20N4O2
C26H17FN4O3
C25H14ClFN4O2
C26H17FN4O2
C22H18N4O2
C21H15FN4O2
Ph
Ph
Ph
-N(n-Pr)2
Ph
-N(n-C5H11 2
)
6g
6h
6i
Ph
-N(n-C6H13 2
)
Ph
-N(n-Bu)2
-N(n-Pr)2
117–118
204–205
171–173
264–265
245–246
237–238
244–245
242–243
288–289
252–254
269–270
4-ClC6H4
4-FC6H4
Ph
6j
-NEt2
6k
6l
C6H5O-
Ph
4-MeC6H4O-
3,4-2Me-C6H3O-
4-MeOC6H4O-
4-ClC6H4O-
2-MeC6H4O-
i-PrO-
6m
6n
6o
6p
6q
6r
Ph
4-FC6H4
4-FC6H4
4-FC6H4
Ph
4-FC6H4
EtO-
aIsolated yields based on iminophosphorane (3).
7-Cyano-2-diethylamino-3,5-diphenyl-3H-pyrrolo[3,2-d]
pyrimidine-4(5H)-one (6d).
1H-NMR (CDCl3): d 0.82
(t, J=7.2Hz, 6H, 2CH3), 3.12 (q, J=7.2Hz, 4H, 2NCH2), 7.24–7.45
(t, J = 7.6 Hz, 4, 2NCH2), 7.22–7.45 (m, 10H, Ar—H), 7.59 (s, 1H,
Ar—H); IR (potassium bromide): 2215 (CN), 1705 (C═O), 1604,
1587, 1554, 1507, 1420, 1259 cmꢀ1; MS: m/z (%) 467 (77, M+), 424
(37), 410 (56), 396 (99), 354 (78), 340 (100), 326 (85), 311 (90),
264 (57), 251 (54), 180 (29), 103 (26), 91 (30), 77 (70).
(m, 10H, Ar—H), 7.61 (s, 1H, Ar—H); IR (potassium bromide):
2218 (CN), 1698 (C═O), 1611, 1589, 1568, 1501, 1239cmꢀ1
;
MS: m/z (%) 383 (23, M+), 354 (97), 311 (30), 278 (62), 264 (34),
235 (29), 209 (32), 180 (50), 103 (39), 77 (100).
7-Cyano-2-dihexylamino-3,5-diphenyl-3H-pyrrolo[3,2-d]
pyrimidine-4(5H)-one (6g).
1H-NMR (CDCl3): d 0.87
7-Cyano-3,5-diphenyl-2-dipropylamino-3H-pyrrolo[3,2-d]
pyrimidine-4(5H)-one (6e).
(t, J= 7.2 Hz, 6H, 2CH3), 1.09–1.28 (m, 16H, 8CH2), 3.01
(t, J= 7.2 Hz, 4H, 2NCH2), 7.22–7.46 (m, 10H, Ar—H), 7.60 ( s, 1H,
Ar—H); IR (potassium bromide): 2218 (CN), 1704 (C═O), 1618,
1588, 1560, 1511, 1427, 1254 cmꢀ1; MS: m/z (%) 495 (61, M+), 438
(36), 424 (45), 410 (100), 354 (49), 340 (64), 326 (82), 311 (82), 264
( 24 ), 251 (33), 180 (22), 103 (26), 77 (66).
1H-NMR (CDCl3): d 0.73
(t, J = 7.2Hz, 6H, 2CH3), 1.22–1.27 (m, 4H, 2CH2), 3.00
(t, J = 7.2 Hz, 4H, 2NCH2), 7.23–7.46 (m, 10H, Ar—H), 7.60 (s,
1H, Ar—H); IR (potassium bromide): 2211 (CN), 1707 (C═O),
1600, 1587, 1565, 1511, 1250cmꢀ1; MS: m/z (%) 411 (100, M+),
368 (54), 340 (83), 311 (72), 292 (55), 264 (78), 100 (47), 77 (85).
7-Cyano-2-dipentylamino-3,5-diphenyl-3H-pyrrolo[3,2-d]
7-Cyano-2-dibutylamino-3,5-diphenyl-3H-pyrrolo[3,2-d]
pyrimidine-4(5H)-one (6h).
1H-NMR (CDCl3): d 0.84
pyrimidine-4(5H)-one (6f).
(t, J = 7.6 Hz, 6H, 2CH3), 1.08–1.26 (m, 12H, 6CH2), 3.02
1H-NMR (CDCl3): d 0.86
(t, J= 7.2 Hz, 6H, 2CH3), 1.15–1.20 (m, 8H, 4CH2), 3.03 (t, J=7.2Hz,
4H, 2NCH2), 7.22–7.44 (m, 10H, Ar—H), 7.60 (s, 1H, Ar—H); IR
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

P. He, Y.-M. Yan, and M.-W. Ding
Vol 000
(potassium bromide): 2211 (CN), 1701 (C═O), 1600, 1585, 1559, 1508,
1433, 1234 cmꢀ1; MS: m/z (%) 439 (62, M+), 410 (34), 396 (51), 382
(100), 339 (91), 311(84), 264 (81), 179 (38), 77 (88).
General preparation of 2-alkoxy-3H-pyrrolo[3,2-d]pyrimidine-
4(5H)-one (6q–6r). To the solution of carbodiimide (4) (3 mmol)
prepared earlier, anhydrous ROH (15 mL) and several drops of
RONa were added. The mixture was stirred at RT for 1–3 h. The
solution was condensed, and the residual was recrystallized from
methylene dichloride/petroleum ether to give 6q–6r.
7-Cyano-3,5-diphenyl-2-isopropoxy-3H-pyrrolo[3,2-d]pyrimidine-
4(5H)-one (6q). 1H-NMR (CDCl3): d 1.26 (d, J = 7.6 Hz, 6H,
2CH3), 5.45–5.50 (m, 1H, OCH), 7.15–7.47 (m, 10H, Ar—H),
7.63 (s, 1H, Ar—H); IR (potassium bromide): 2209 (CN), 1689
(C═O), 1583, 1547, 1223 cmꢀ1; MS: m/z (%) 370 (32, M+), 328
(100), 236 (50), 209 (89), 181 (33), 154 (53), 77 (34).
3-(4-Chlorophenyl)-7-cyano-2-dipropylamino-5-phenyl-3H-
pyrrolo[3,2-d]pyrimidine-4(5H)-one (6i).
1H-NMR (CDCl3):
d 0.76 (t, J = 7.2 Hz, 6H, 2CH3), 1.27–1.33 (m, 4H, 2CH2), 3.00
(t, J = 7.2 Hz, 4H, 2NCH2), 7.19–7.44 (m, 9H, Ar—H), 7.61
(s, 1H, Ar—H); IR (potassium bromide): 2215 (CN), 1685
(C═O), 1604, 1577, 1567, 1503, 1240 cmꢀ1; MS: m/z (%) 445
(40, M+), 404 (90), 374 (100), 345 (65), 306 (38), 264 (48), 153
(24), 111 (24), 77 (64).
7-Cyano-2-diethylamino-3-(4-fluorophenyl)-5-phenyl-3H-
pyrrolo[3,2-d]pyrimidine-4(5H)-one (6j). 1H-NMR (CDCl3):
d 0.88 (t, J = 7.2 Hz, 6H, 2CH3), 3.11 (q, J = 7.2 Hz, 4H, 2NCH2),
7.14–7.44 (m, 9H, Ar—H), 7.60 (s, 1, Ar—H); IR (potassium
bromide): 2211 (CN), 1701 (C═O), 1598, 1584, 1542, 1505,
1234 cmꢀ1; MS: m/z (%) 401 (59, M+), 371 (100), 329 (53),
278 (42), 264 (39), 153 (19), 121 (25), 103 (20), 95 (25), 77 (50).
7-Cyano-2-ethoxy-3-(4-fluorophenyl)-5-phenyl-3H-pyrrolo[3,2-d]
pyrimidine-4(5H)-one (6r).
1H-NMR (CDCl3):
d
1.28
(t, J = 7.2 Hz, 3H, CH3), 4.51 (q, J = 7.2 Hz, 2H, OCH2),
7.14–7.45 (m, 9H, Ar—H), 7.64 (s, 1H, Ar—H); IR (potassium
bromide): 2198 (CN), 1701 (C═O), 1576, 1541, 1210 cmꢀ1; MS:
m/z (%) 374 (92, M+), 346 (71), 252 (20), 236 (49), 209 (100),
181 (32), 154 (41), 103 (44), 77 (40).
General preparation of 2-aryloxy-3H-pyrrolo[3,2-d]pyrimidine-
4(5H)-one (6k–6p). To the solution of carbodiimide (4) (3mmol)
prepared earlier in anhydrous acetonitrile (15 mL), phenol (3mmol)
and potassium carbonate (0.2g, 1.5 mmol) were added. The
mixture was stirred at 40–50ꢁC for 3–8 h. After cooling, 30mL
water was added, and stir was continued until all the product was
precipitated, then filtered and washed with ethanol; the residual
wasrecrystallized from methylenedichloride/ethanoltogive6k–6p.
7-Cyano-3,5-diphenyl-2-phenoxy-3H-pyrrolo[3,2-d]pyrimidine-4
(5H)-one (6k). 1H-NMR (CDCl3): d 7.51–7.16 (m, 15H, Ar—H),
7.64 (s, 1H, Ar—H); IR (potassium bromide): 2207 (CN), 1700
(C═O), 1601, 1549, 1235, 1221 cmꢀ1; MS: m/z (%) 404 (80, M+),
311 (22), 285 (100), 256 (9), 180 (15), 153 (9), 103 (7), 77 (33).
7-Cyano-3,5-diphenyl-2-(4-methylphenoxy)-3H-pyrrolo[3,2-d]
pyrimidine-4(5H)-one (6l). 1H-NMR (CDCl3): d 2.36 (s, 3H,
CH3), 7.02–7.52 (m, 14H, Ar—H), 7.64 (s, 1H, Ar—H); IR
(potassium bromide): 2178 (CN), 1702 (C═O), 1594, 1548,
1230 cmꢀ1; MS: m/z (%) 418 (16, M+), 311 (10), 299 (100), 180
(29), 153 (19), 103 (17), 77 (79).
Acknowledgment. We gratefully acknowledge financial support of
this work by the National Natural Science Foundation of China
(No. 21172085) and the Educational Commission of Hubei Province
of China (No. Q20122509).
REFERENCES AND NOTES
[1] Grahner, B.; Winiwarter, S.; Lanzner, W.; Mueller, C. E. J Med
Chem 1994, 37, 1526.
[2] Miles, R. W.; Tyler, P. C.; Furneaux, R. H.; Bagdassarian, C. K.;
Schramm, V. L. Biochemistry 1998, 37, 8615.
[3] Gandhi, V.; Kilpatrick, J. M.; Plunkett, W.; Ayres, M.; Harman,
L.; Du, M.; Bantia, S.; Davisson, J.; Wierda, W. G.; Faderl, S.; Kantarjian,
H.; Thomas, D. Blood 2005, 106, 4253.
[4] Schramm, V. L. Nucleos Nucleot Nucl 2004, 23, 1305.
[5] Kamath, V. P.; Juarez-Brambila, J. J.; Morris, C. B.; Winslow,
C. D.; Morris, P. E. Org Process Res Dev 2009, 13, 928.
[6] Otmar, M.; Masojıdková, M.; Votruba, I.; Holý, A. Bioorg Med
Chem 2004, 12, 3187.
7-Cyano-2-(3,4-dimethylphenoxy)-3,5-diphenyl-3H-pyrrolo
[3,2-d]pyrimidine-4(5H)-one (6m). 1H-NMR (CDCl3): d 2.25
(s, 6H, 2CH3), 6.89–7.52 (m, 13H, Ar—H), 7.63 (s, 1H, Ar—H); IR
(potassium bromide): 2194 (CN), 1705 (C═O), 1603, 1556, 1267,
1209cmꢀ1; MS: m/z (%) 432 (100, M+), 313 (94), 298 (25), 180
(13), 103 (12), 91 (27), 77 (81).
7-Cyano-3-(4-fluorophenyl)-2-(4-methoxyphenoxy)-5-phenyl-
3H-pyrrolo[3,2-d]pyrimidine-4(5H)-one (6n). 1H-NMR (CDCl3):
d 3.82 (s, 3H, OCH3), 6.91–7.44 (m, 13H, Ar—H), 7.64 (s, 1H,
Ar—H); IR (potassium bromide): 2187 (CN), 1707 (C═O), 1592,
1534, 1245, 1208 cmꢀ1; MS: m/z (%) 452 (74, M+), 329 (16), 315
(100), 300 (57), 272 (28), 180 (9), 77 (8).
2-(4-Chlorophenoxy)-7-cyano-3-(4-fluorophenyl)-5-phenyl-
3H-pyrrolo[3,2-d]pyrimidine-4(5H)-one (6o). 1H-NMR
(CDCl3): d 7.11–7.46 (m, 13H, Ar—H), 7.65 (s, 1H, Ar—H); IR
(potassium bromide): 2196 (CN), 1701 (C═O), 1589, 1545, 1233,
1211cmꢀ1; MS: m/z (%) 456 (50, M+), 319 (100), 284 (96), 256
(18), 180 (41), 153 (26), 121 (12), 99 (21), 77 (84).
[7] Pudziuvelyte, E.; Ríos-Luci, C.; León, L. G.; Cikotiene, I.;
Padrón, J. M. Bioorg Med Chem 2009, 17, 4955.
ꢀꢀ
[8] Otmar, M.; Masojídková, M.; Budesínský, M.; Holý, A.
Tetrahedron 1998, 54, 2931.
[9] Otmar, M.; Masojídková, M.; Holý, A. Tetrahedron 1997,
53, 391.
[10] Zhao, L.; Tao, K.; Li, H.; Zhang, J. Tetrahedron 2011, 67, 2803.
[11] Evans, G. B.; Furneaux, R. H.; Hutchison, T. L.; Kezar,
H. S.; Morris, P. E.; Schramm, V. L.; Tyler, P. C. J Org Chem 2001,
66, 5723.
[12] Salaheldin, A. M.; Oliveira-Campos, A. M. F.; Rodrigues, L.
M. Arkivoc 2008, xiv, 180.
[13] Garcia-Lopez, M. T.; de las Heras, F. G.; Stud, M. J Chem Soc
Perkin Trans 1 1978, 483.
[14] Lim, M. I.; Ren, W. Y.; Otter, B. A.; Klein, R. S. J Org Chem
1983, 48, 780.
[15] Palacios, F.; Alonso, C.; Aparicio, D.; Rubiales, G.; de los
Santos, J. M. Tetrahedron 2007, 63, 523.
[16] Fresneda, P. M.; Molina, P. Synlett 2004, 1.
[17] Marsden, S. P.; McGonagle, A. E.; McKeever-Abbas, B. Org
Lett 2008, 10, 2589.
7-Cyano-3-(4-fluorophenyl)-2-(2-methylphenoxy)-5-phenyl-3H-
1H-NMR (CDCl3):
[18] Wang, H. Q.; Zhou, W. P.; Wang, Y. Y.; Lin, C. R. J Agric
Food Chem 2008, 56, 7321.
[19] Smith, C. J.; Smith, C. D.; Nikbin, N.; Ley, S. V.; Baxendale,
I. R. Org Biomol Chem 2011, 9, 1927.
pyrrolo[3,2-d]pyrimidine-4(5H)-one (6p).
2.10 (s, 3H, CH3), 7.16–7.47 (m, 13H, Ar—H), 7.63 (s, 1H,
d
Ar—H); IR (potassium bromide): 2201 (CN), 1703 (C═O), 1585,
1543, 1229 cmꢀ1; MS: m/z (%) 436 (19, M+), 329 (14), 299 (34),
218 (8), 180 (15), 153 (25), 121 (23), 95 (30), 77 (100).
[20] Ramazani, A.; Rezaei, A. Org Lett 2010, 12, 2852.
[21] Huang, N. Y.; Nie, Y. B.; Ding, M. W. Synlett 2009, 611.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
3H-Pyrrolo[3,2-d]pyrimidin-4(5H)-one Derivatives
[22] Huang, N. Y.; Liang, Y. J.; Ding, M. W.; Fu, L. W.; He, H. W.
[25] Xu, S. Z.; Wu, J.; Cao, M. H.; Ding, M. W. J Heterocycl Chem
2010, 47, 68.
[26] He, P.; Nie, Y. B.; Wu, J.; Ding, M. W. Org Biomol Chem
2011, 9, 1429.
[27] Gewald, K.; Schäfer, H.; Bellmann, P.; Hain, U. J Prakt Chem /
Chem-Ztg 1992, 334, 491.
Bioorg Med Chem Lett 2009, 19, 831.
[23] Liu, M. G.; Hu, Y. G.; Ding, M. W. Tetrahedron 2008,
64, 9052.
[24] Li, W. J.; Liu, M.; Feng, L. L.; Ding, M. W. Chem Res Chin
Univ 2010, 26, 60.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet