Efficient synthesis of benzothieno[3,2-d]-1,2,4-triazolo [1,5-a]pyrimidin-5(1H)-ones via a tandem aza-Wittig/heterocumulene-mediated annulation

Article abstract of DOI:10.1002/jhet.158

(Chemical Equation Presented) The carbodiimides 2, obtained from reactions of iminophosphorane 1 with isocyanates, reacted with hydrazine to give selectively 3-amino-2-arylaminobenzothieno[3,2-d]pyrimidin-4(3H)-ones 4. Reactions of 4 with triphenylphosphi

Full text of DOI:10.1002/jhet.158

September 2009
Efficient Synthesis of Benzothieno[3,2-d]-1,2,4-triazolo
[1,5-a]pyrimidin-5(1H)-ones via a Tandem aza-Wittig/
Heterocumulene-Mediated Annulation
903
Sheng-Zhen Xu,a,b Min-Hui Cao,b Chang-Shui Chen,b and Ming-Wu Dinga*
aKey Laboratory of Pesticide and Chemical Biology of Ministry of Education, Central China
Normal University, Wuhan 430079, People’s Republic of China
bCollege of Basic Science, HuaZhong Agricultural University, Wuhan 430070,
People’s Republic of China
*E-mail: ding5229@yahoo.com.cn
Received November 5, 2008
DOI 10.1002/jhet.158
Published online 2 September 2009 in Wiley InterScience (www.interscience.wiley.com).
The carbodiimides 2, obtained from reactions of iminophosphorane 1 with isocyanates, reacted with
hydrazine to give selectively 3-amino-2-arylaminobenzothieno[3,2-d]pyrimidin-4(3H)-ones 4. Reactions
of 4 with triphenylphosphine, hexachloroethane, and Et3N produced iminophosphoranes 5. A tandem
aza-Wittig reaction of iminophosphorane 5 with isocyanate, acyl chloride generated benzothieno[3,2-d]-
1,2,4-triazolo[1,5-a]pyrimidin-5(1H)-ones 7 and 9 in satisfactory yields. The effects of the nucleophiles
on cyclization have been investigated.
J. Heterocyclic Chem., 46, 903 (2009).
INTRODUCTION
reaction, with the aim of evaluating their fungicidal
activities [16–20]. Reported herein is a new efficient
synthesis of 2-substituted benzothieno[3,2-d]-1,2,4-tria-
zolo[1,5-a] pyrimidin-5(1H)-one 7 and 9 from easily
accessible iminophosphorane 1 [21].
Thienopyrimidines are very important heterocycles
because of their significant antifungal and antibacterial
activities [1–4] as well as their good anticonvulsant and
angiotensin or H1 receptor antagonistic activities [5–7].
The chemistry of thienopyrimidinones have also
received attention because of their starting materials, 2-
amino-3-carboxythiophenes, which can be conveniently
synthesized. On the other hand, heterocycles containing
1,2,4-triazole nucleus also exhibit various biological
activities; several of them have been used as fungicidal,
bactericidal, insecticidal, antitumor, and anti-inflamma-
tory agents [8–13]. The introduction of a triazole ring
into the thienopyrimidine system is expected to influ-
ence the biological activities significantly.
RESULTS AND DISCUSSION
Carbodiimides 2, obtained from aza-Wittig reactions of
iminophosphorane 1 with aromatic or alkyl isocyanates,
reacted with hydrazine to give selectively 2-arylamino-3-
aminobenzothieno[3,2-d]pyrimidin-4(3H)-ones 4 in 80–
87% yields at room temperature (Table 1, Scheme 1).
The formation of 4 can be rationalized in terms of an
initial nucleophilic addition of hydrazine to give inter-
mediate 3 which directly cyclized across the strong
nucleophilic hydrazine group rather than the aryl(alkyl)-
amine one. Compounds 4 were further converted to
functionalized iminophosphoranes 5 via reaction with
triphenylphosphine, hexachloroethane, and Et3N in
72–78% yields (Table 1, Scheme 1).
The aza-Wittig reactions of iminophosphoranes have
received increasing attention in view of their useful util-
ities in the synthesis of nitrogen heterocyclic compounds
under mild conditions [14,15]. Recently, we have been
interested in the synthesis of triazolo-quinazolinones,
thienopyrimidinones, and imidazolinones via aza-Wittig
C
V
2009 HeteroCorporation

Table 1
Physical and analytical data of compounds 7.
Analysis %
(Calcd./Found)
Comp.
R1
R2 or R3
Time (hours)
2
Mp (ꢀC)
246–247
Yield %a
80
Molecular Formula
C16H14N4OS
C
H
N
4a
Ph
62.32
62.08
56.07
56.29
63.33
63.12
56.91
56.79
58.31
58.19
71.82
71.78
67.71
67.58
72.15
72.02
69.65
69.82
70.05
70.22
68.07
68.19
67.47
67.60
62.95
63.08
57.75
57.88
62.23
62.38
68.63
68.75
62.05
62.18
68.07
68.18
58.60
58.48
59.50
59.58
59.80
59.88
63.98
64.05
64.76
64.68
65.49
65.54
60.82
60.92
64.76
64.85
61.52
61.59
67.36
67.39
65.04
65.29
70.03
70.22
3.92
3.74
3.23
3.12
4.38
4.16
5.14
5.43
5.59
5.33
4.43
4.54
4.01
4.24
4.67
4.84
5.09
5.24
5.33
5.45
4.05
4.11
3.69
3.73
3.52
5.57
2.74
2.67
3.18
3.23
4.38
4.44
3.52
3.54
4.05
3.96
3.93
4.05
4.28
4.45
5.61
5.85
4.56
4.75
4.92
5.15
5.25
5.45
5.95
6.25
4.92
5.13
5.16
5.03
4.85
4.67
3.64
3.77
3.58
3.67
18.17
18.37
16.34
16.57
17.38
17.25
20.42
20.11
11.12
11.22
9.85
4b
4c
4d
4e
5a
5b
5c
5d
5e
7a
7b
7c
7d
7e
7f
4-ClC6H4
4-CH3C6H4
i-Pr
2
2
>300
82
83
79
77
74
72
78
77
75
84
82
86
85
84
85
83
86
76
74
77
80
83
67
72
82
72
65
74
62
C16H11ClN4OS
C17H14N4OS
>300
2
207–208
199–201
258–260
260–261
259–261
207–208
202–204
>300
C
C
C
13H14N4OS
14H16N4OS
34H25N4OPS
n-Bu
2
Ph
6
9.77
9.29
9.17
9.62
4-ClC6H4
4-CH3C6H4
i-Pr
6
C34H24ClN4OPS
C35H27N4OPS
C31H27N4OPS
C32H29N4OPS
C24H17N5OS
C23H15N5OS
C24H16ClN5OS
C23H13ClN5OS
C23H14ClN5OS
C25H19N5OS
C24H16ClN5OS
C24H17N5OS
C20H16ClN5OS
C21H18ClN5OS
C17H19N5OS
C20H17N5OS
C21H19N5OS
C22H21N5OS
6
9.52
6
10.48
10.42
10.21
10.05
16.54
16.37
17.10
17.00
15.29
15.14
14.64
14.69
15.78
15.69
16.01
15.86
15.29
15.16
16.54
16.65
17.09
16.98
16.52
16.35
20.51
20.39
18.65
18.50
17.98
17.89
17.36
17.19
19.70
19.57
17.98
17.79
17.93
17.97
14.96
14.98
14.86
14.65
14.20
14.01
n-Bu
6
4-CH3C6H4
Ph
Ph
4
Ph
4
>300
4-CH3C6H4
4-ClC6H4
Ph
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-CH3C6H4
4-CH3C6H4
4-CH3C6H4
i-Pr
4
>300
4
>300
4
>300
4-CH3C6H4
4-ClC6H4
Ph
4
>300
7g
7h
7i
4
298–299
290–291
>300
4
4-ClC6H4
4-ClC6H4
i-Pr
8
7j
n-Bu
8
282–284
>300
7k
7l
i-Pr
8
i-Pr
Ph
8
>300
7m
7n
7o
7p
9a
9b
9c
9d
Ph
4-CH3C6H4
4-CH3C6H4
i-Pr
4
>300
n-Bu
8
>300
n-Bu
8
>300
C
C
18H21N5OS
21H19N5OS
n-Bu
Ph
8
294–296
187–189
212–214
>300
n-Bu
CH3
24
24
24
24
C16H19N4OS
21H18N4OS
C18H12N4OS
23H14N4OS
n-Bu
Ph
C
Ph
CH3
Ph
Ph
277–279
C
a Yields based on iminophosphorane 1 or 5.

September 2009 Efficient Synthesis of Benzothieno[3,2-d]-1,2,4-triazolo
[1,5-a]pyrimidin-5(1H)-ones via a Tandem aza-Wittig/Heterocumulene-Mediated Annulation
905
Scheme 1
Scheme 3
iminophosphorane 5 and acyl chloride in the presence of
Et3N affording the intermediate imidoyl chloride 8,
which undergoes cyclization to give 9.
The structure of the synthesized compound 5, 7, 9
were confirmed by their spectral data. For example, the
IR spectra of 7k revealed C¼¼O absorption bands at
When iminophosphoranes 5 in anhydrous CH2Cl2
were treated with isocyanate at room temperature, the
color of the reaction mixture quickly turned red, disap-
pearing after few minutes, and 2-aminobenzothieno[3,2-
d]-1,2,4-triazolo-[1,5-a]pyrimdin-5(1H)-ones 7 were iso-
lated as crystalline solids in good yields (67–86%, Table
1, Scheme 2). Presumably, the conversion of 5 into 7
involves initial aza-Wittig reaction between the imino-
phosphorane 5 and the isocyanate to give a carbodiimide
6 as highly reactive intermediate, which easily under-
goes ring closure across the amino group to give the
otherwise not readily available 2-amino substituted ben-
1
1672 cmꢁ1. The H NMR spectral data of 7k show the
signals of ANH at 9.89 ppm as singlet. The ArAH sig-
nals appeared at 7.50–8.34 (m, 4H, ArAH). The MS
spectrum of 7k shows an obvious molecule ion peak at
m/z 341 with 34% abundance.
In summary, we have developed an efficient synthesis
of 2-substituted benzothieno[3,2-d]-1,2,4-triazolo[1,5-a]
pyrimidin-5(1H)-one. Due to the easily accessible and
versatile starting material, this method has the potential
in the synthesis of many biologically and pharmaceuti-
cally active thienopyrimidinones derivatives.
zothieno[3,2-d]-1,2,4-triazolo[1,5-a]
pyrimidin-5(1H)-
ones 7. It is noteworthy that the reaction can be easily
carried out at room temperature under mild, neutral con-
dition, and the separation of 7 from the reaction mixture
was also easily carried out by simple filtration.
EXPERIMENTAL
Melting points were determined using a X-4 model appara-
tus and were uncorrected. MS were measured on a Finnigan
Trace MS spectrometer. NMR spectra were recorded in CDCl3
on a Varian Mercury Plus 400 (400 Hz) spectrometer and
chemical shifts (d) were given in ppm using (CH3)4Si as an in-
ternal reference (d ¼ 0). IR were recorded on a PE-983 infra-
Iminophosphorane 5 reacted with acyl chlorides in the
presence of Et3N in CH2Cl2 at room temperature to give
2-substituted
pyrimidin-5(1H)-ones
benzothieno[3,2-d]-1,2,4-triazolo[1,5-a]
in good yields (62–74%,
9
Table 1, Scheme 3). The formation of 9 can be
viewed as an initial aza-Wittig reaction between the
red spectrometer as KBr pellets with absorption in cmꢁ1
.
Elementary analyses were taken on a Vario EL III elementary
analysis instrument.
Preparation of compounds 4. To a solution of imino-phos-
phorane 1 (1.44 g, 3 mmol) in anhyd. CH2Cl2 (10 mL) was
added isocyanate (3 mmol) under N2 at r.t. After the reaction
mixture was left unstirred for 8–12 h at 0–5ꢀC, the solvent
was removed off under reduced pressure and Et2O/petroleum
ether (1:2, 12 mL) was added to precipitate triphenylphosphine
oxide. Removal of the solvent gave carbodiimides 2, which
were used directly without further purification. To the solution
of 2 prepared above in CH2Cl2 (10 mL) was added hydrazine
(0.18 g, 3 mmol). The mixture was stirred for 2 h at r. t. and
filtered to give 4.
Scheme 2
3-Amino-2-phenylamino-benzo[4,5]thieno[3,2-d]pyrimidin-
1
4(3H)-one (4a). H NMR (400 MHz, CDCl3): d (ppm): 4.65
(s, 1H, NH), 4.72 (s, 2H, NH2), 7.15–8.06 (m, 9H, ArAH). IR
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

906
S.-Z. Xu, M.-H. Cao, C.-S. Chen, and M.-W. Ding
Vol 46
(KBr): 3412 (NH), 1674 (C¼¼O), 1530, 1380, 698 cmꢁ1. MS:
m/z (%) 308 (47, Mþ), 292 (33), 200 (19), 145 (28), 77 (87).
3-Amino-2-(4-chlorophenylamino)-benzo[4,5]thieno[3,2-d]
2CH3), 3.94 (m, 1H, NCH), 4.60 (s, 1H, NH), 7.23–8.20 (m,
19H, ArAH). IR (KBr): 3430 (NH), 1673 (C¼¼O), 1531, 1377,
696 cmꢁ1. MS: m/z (%) 534 (47, Mþ), 272 (37), 200 (37), 146
(68), 77 (79).
1
pyrimidin-4(3H)-one (4b). H NMR (400 MHz, CDCl3): d
(ppm): 4.71 (s, 1H, NH), 4.86 (s, 2H, NH2), 7.43–7.68 (m, 6H,
ArAH), 7.87 (d, J ¼ 8.0 Hz, 1H, ArAH), 8.25 (d, J ¼ 7.6 Hz,
1H, ArAH). IR (KBr): 3428 (NH), 1676 (C¼¼O), 1531, 1385,
693 cmꢁ1. MS: m/z (%) 342 (35, Mþ), 327 (24), 200 (34), 146
(43), 77 (26).
2-(Butylamino)-3-(triphenylphosphoranylidene)aminobenzo
[4,5]thieno[3,2-d]pyrimidin-4(3H)-one (5e). H NMR (400
1
MHz, CDCl3) d (ppm): 0.90 (t, J ¼ 7.0 Hz, 3H, CH3), 1.22–
1.37 (m, J ¼ 7.0 Hz, 4H, 2CH2), 3.50(m, 2H, NCH2), 4.61 (s,
1H, NH), 7.27–8.22 (m, 19H, ArAH). IR (KBr): 3431 (NH),
1671 (C¼¼O), 1529, 1376, 697 cmꢁ1. MS: m/z (%) 548 (58,
Mþ), 286 (25), 200 (56), 146 (52), 77 (71).
3-Amino-2-(4-methylphenylamino)-benzo[4,5]thieno[3,2-d]
1
pyrimidin-4(3H)-one (4c). H NMR (400 MHz, CDCl3): d
(ppm): 2.66 (s, 3H, CH3), 4.73 (s, 1H, NH), 4.77 (s, 2H, NH2),
7.23–8.46 (m, 8H, ArAH). IR (KBr): 3420 (NH), 1678
(C¼¼O), 1531, 1377, 693 cmꢁ1. MS: m/z (%) 322 (52, Mþ),
306 (47), 200 (34), 146 (52), 77 (47).
General procedure for the preparation of 2-arylamino
benzothieno[3,2-d]-1,2,4-triazolo[1,5-a]pyrimidin-5(1H)-ones
7a–7p. To a solution of iminophosphorane 5 (1 mmol) in
anhyd. CH2Cl2 (15 mL) was added aromatic isocyanate
(1 mmol) under N2 at r.t. The color of the reaction mixture
became red, then decolorized after few minutes. The colorless
solution was stirred at r.t for 4–8 h. The white precipitated
solid was collected by filtration and recrystallized from
CH2Cl2AEtOH to give 7a–7p.
3-Amino-2-isopropylamino-benzo[4,5]thieno[3,2-d]pyrimi-
1
din-4(3H)-one (4d). H NMR (400 MHz, CDCl3) d (ppm):
1.16 (d, J ¼ 6.4 Hz, 6H, 2CH3), 3.40–3.60 (m, 1H, NCH),
4.66 (d, J ¼ 6.8 Hz, 1H, NH), 4.74 (s, 2H, NH2), 7.40–7.61
(m, 2H, ArAH), 7.83 (d, J ¼ 8.4 Hz, 1H, ArAH), 8.15 (d, J
¼ 7.6 Hz, 1H, ArAH). IR (KBr): 3417 (NH), 1676 (C¼¼O),
1535, 1371, 694 cmꢁ1. MS: m/z (%) 274 (47, Mþ), 258 (17),
200 (47), 146 (44), 77 (45).
1-(4-Methylphenyl)-2-phenylamino-benzo[4,5]thieno[3,2-d]
1
[1,2,4]triazolo[1,5-a]pyrimidin-5(1H)-one (7a). H NMR (400
MHz, CDCl3/TFA) d (ppm): 2.54 (s, 3H, CH3), 6.72–8.07 (m,
13H, ArAH). IR (KBr): 3409 (NH), 1671 (C¼¼O), 1575, 1487,
737 cmꢁ1. MS: m/z (%) 422 (43, Mþ), 277 (62), 201 (28), 146
(86), 91 (77), 77 (58).
3-Amino-2-butylamino-benzo[4,5]thieno[3,2-d]pyrimidin-
1
4-(3H)-one (4e). H NMR (400 MHz, CDCl3): d (ppm): 0.92
(t, J ¼ 7.0 Hz, 3H, CH3), 1.20–1.37 (m, 4H, CH2), 3.55
(m, 2H, NCH2), 4.61 (s, 1H, NH), 4.75 (s, 2H, NH2), 7.43–
7.58 (m, 2H, ArAH), 7.85 (d, J ¼ 8.0 Hz, 1H, ArAH), 8.26
(d, J ¼ 7.6 Hz, 1H, ArAH). IR (KBr): 3411 (NH), 1676
(C¼¼O), 1533, 1372, 694 cmꢁ1. MS: m/z (%) 288 (58, Mþ),
272 (31), 200 (55), 146 (37), 77 (58).
Preparation of iminophosphorane 5. To a mixture of 4
(8 mmol), PPh3 (3.14 g, 12 mmol) and C2Cl6 (2.84 g, 12
mmol) in dry CH3CN (40 mL), was added dropwise NEt3
(2.42 g, 24 mmol) at room temperature. The color of the reac-
tion mixture quickly turned yellow and the mixture was stirred
4–6 h at room temperature. After completion of the reaction
(monitored with TLC), the solvent was removed under reduced
pressure and the residue was recrystallized from EtOH to give
iminophosphoranes 5.
1-Phenyl-2-phenylamino-benzo[4,5]thieno[3,2-d][1,2,4]
tri-azolo[1,5-a]pyrimidin-5(1H)-one (7b). 1H NMR (400
MHz, CDCl3/TFA) d (ppm): 7.10–8.13 (m, 14H, ArAH). IR
(KBr): 3412 (NH), 1671 (C¼¼O), 1577, 1490, 744 cmꢁ1. MS:
m/z (%) 408 (67, Mþ), 277 (78), 201 (22), 146 (93), 77 (100).
2-(4-Chloro-phenylamino)-1-(4-methylphenyl)-benzo[4,5]-
1
thieno[3,2-d][1,2,4]triazolo[1,5-a]pyrimidin-5(1H)-one (7c). H
NMR (400 MHz, CDCl3/TFA) d (ppm): 2.55 (s, 3H, CH3),
6.88–8.03 (m, 12H, ArAH). IR (KBr): 3421 (NH), 1672
(C¼¼O), 1572, 1496, 743 cmꢁ1. MS: m/z (%) 457 (23, Mþ),
277 (64), 200 (35), 146 (90), 91 (77), 77 (76).
1-(4-Chlorophenyl)-2-(4-chloro-phenylamino)-benzo[4,5]-
1
thieno[3,2-d][1,2,4]triazolo[1,5-a]pyrimidin-5(1H)-one (7d). H
NMR (400 MHz, CDCl3/TFA) d (ppm): 6.82–8.09 (m, 12H,
ArAH). IR (KBr): 3420 (NH), 1673 (C¼¼O), 1574, 1492, 742
cmꢁ1. MS: m/z (%) ¼ 477 (34, Mþ), 277 (75), 201 (19), 145
(89), 77 (63).
2-Phenylamino-3-(triphenylphosphoranylidene)aminoben-
zo[4,5]thieno[3,2-d]pyrimidin-4(3H)-one
1
(5a). H
NMR
(400 MHz, CDCl3) d (ppm): 4.66 (s, 1H, NH), 7.09–8.25
(m, 24H, ArAH). IR (KBr): 3420 (NH), 1670 (C¼¼O), 1533,
1381, 696 cmꢁ1. MS: m/z (%) 568 (52, Mþ), 292 (20), 276
(57), 200 (13), 145 (24), 77 (50).
2-(4-Chloro-phenylamino)-1-phenyl-benzo[4,5]thieno[3,2-d]
1
[1,2,4]triazolo[1,5-a]pyrimidin-5(1H)-one (7e). H NMR (400
MHz, CDCl3/TFA) d (ppm): 7.19–8.08 (m, 13H, ArAH). IR
(KBr): 3421 (NH), 1673 (C¼¼O), 1573, 1490, 743 cmꢁ1. MS:
m/z (%) ¼ 442 (50, Mþ), 277 (67), 201 (32), 145 (87), 77
(61).
2-(4-Chlorophenyl)amino-3-(triphenylphosphoranylidene)
amino-benzo[4,5]thieno[3,2-d]pyrimidin-4(3H)-one (5b). H
1
NMR (400 MHz, CDCl3) d (ppm): 4.73 (s, 1H, NH), 7.20–
8.30 (m, 23H, ArAH). IR (KBr): 3428 (NH), 1676 (C¼¼O),
1531, 1385, 693 cmꢁ1. MS: m/z (%) 602 (32, Mþ), 327 (9),
276 (26), 200 (12), 146 (51), 77 (22).
1-(4-Methylphenyl)-2-(4-methyl-phenylamino)-benzo[4,5]-
1
thieno[3,2-d][1,2,4]triazolo[1,5-a]pyrimidin-5(1H)-one (7f). H
NMR (400 MHz, CDCl3/TFA) d (ppm): 1.80 (s, 3H, CH3),
2.54 (s, 3H, CH3), 6.72–8.02 (m, 12H, ArAH). IR (KBr): 3419
(NH), 1671 (C¼¼O), 1575, 1493, 742 cmꢁ1. MS: m/z (%) 436
(29, Mþ), 277 (64), 201 (19), 146 (84), 91 (73), 77 (89).
1-(4-Chlorolphenyl)-2-(4-methyl-phenylamino)-benzo[4,5]
2-(4-Methylphenyl)amino-3-(triphenylphosphoranylidene)
amino-benzo[4,5]thieno[3,2-d]pyrimidin-4(3H)-one (5c). H
1
NMR (400 MHz, CDCl3) d (ppm): 2.55 (s, 3H, CH3), 4.78 (s,
1H, NH), 7.23–8.46 (m, 23H, ArAH). IR (KBr): 3434 (NH),
1668 (C¼¼O), 1529, 1378, 690 cmꢁ1. MS: m/z (%) 582 (56,
Mþ), 306 (31), 200 (14), 146 (55), 77 (83).
1
thieno[3,2-d][1,2,4]triazolo[1,5-a]pyrimidin-5(1H)-one (7g). H
NMR (400 MHz, CDCl3/TFA) d (ppm): 2.41 (s, 3H, CH3),
7.40–8.00 (m, 12H, ArAH). IR (KBr): 3422 (NH), 1672
(C¼¼O), 573, 1490, 744 cmꢁ1. MS: m/z (%) 457 (65, Mþ), 277
(58), 200 (31), 146 (82), 91 (67), 77 (78).
2-(Isopropylamino)-3-(triphenylphosphoranylidene)
aminobenzo[4,5]thieno[3,2-d]pyrimidin-4(3H)-one
1
(5d). H
NMR (400 MHz, CDCl3) d (ppm): 1.17 (d, J ¼ 6.4 Hz, 6H,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

September 2009 Efficient Synthesis of Benzothieno[3,2-d]-1,2,4-triazolo
[1,5-a]pyrimidin-5(1H)-ones via a Tandem aza-Wittig/Heterocumulene-Mediated Annulation
907
2-(4-Methyl-phenylamino)-1-phenyl-benzo[4,5]thieno[3,2-d]
[1,2,4]triazolo[1,5-a]pyrimidin-5(1H)-one (7h). H NMR (400
MHz, CDCl3/TFA) d (ppm): 2.03 (s, 3H, CH3), 6.76–8.06 (m,
13H, ArAH). IR (KBr): 3412 (NH), 1671 (C¼¼O), 1577, 1491,
742 cmꢁ1. MS: m/z (%) 423 (54, Mþ), 277 (56), 201 (25), 146
(85), 91 (66), 77 (79).
General procedure for the preparation of 2-substituted
benzothieno[3,2-d]-1,2,4-triazolo[1,5-a]pyrimidin-5(1H)-ones
9a–9d. To a solution of iminophosphorane 5 (2 mmol) in
anhyd. CH2Cl2 (10 mL) were added acyl chloride (2 mmol)
and Et3N (0.20 g, 2 mmol) under N2 at r.t. The solution was
stirred at r.t for 24 h. The white precipitated ammonium salt
was separated by filtration and the filtrate was concentrated to
dryness. The residue was recrystallized from CH2Cl2AEtOH to
give 9a–9d.
1
1-(4-Chlorophenyl)-2-isopropylamino-benzo[4,5]thieno-[3,2-d]
1
[1,2,4]triazolo[1,5-a]pyrimidin-5(1H)-one (7i). H NMR (400
MHz, CDCl3/TFA) d (ppm): 1.33 (d, J ¼ 7.0 Hz, 6H, 2CH3),
4.09 (d, J ¼ 6.9 Hz, 1H, NCH), 7.37–8.14 (m, 8H, ArAH). IR
(KBr): 3414 (NH), 1672 (C¼¼O), 1567, 1489, 743 cmꢁ1. MS:
m/z (%) 409 (46, Mþ), 277 (46), 201 (22), 145 (100), 77 (69).
2-Butylamino-1-(4-chlorophenyl)-benzo[4,5]thieno[3,2-d]-
1-Butyl-2-methyl-benzo[4,5]thieno[3,2-d][1,2,4]triazolo-[1,5-a]
1
pyrimidin-5(1H)-one (9a). H NMR (400 MHz, CDCl3) d
(ppm): 1.02 (t, J ¼ 7.0 Hz, 3H, CH3), 1.40–1.49 (m, 2H,
CH2), 1.81–1.88 (m, 2H, CH2), 2.57 (s, 3H, CH3), 4.13 (t, J ¼
6.9 Hz, 2H, NCH2), 7.42–8.26 (m, 4H, ArAH). IR (KBr):
1672 (C¼¼O), 1572, 1493, 740 cmꢁ1. MS: m/z (%) 312 (57,
Mþ), 277 (69), 201 (17), 145 (60), 77 (86).
1
[1,2,4]triazolo[1,5-a]pyrimidin-5(1H)-one (7j). H NMR
(400 MHz, CDCl3/TFA) d (ppm): 0.93 (t, J ¼ 7.0 Hz, 3H,
CH3), 1.31–1.38 (m, 2H, CH2), 1.60–1.69 (m, 2H, CH2), 3.44
(t, J ¼ 6.9 Hz, 2H, NCH2), 7.47–8.13 (m, 8H, ArAH). IR
(KBr): 3415 (NH), 1673 (C¼¼O), 1566, 1488, 742 cmꢁ1. MS:
m/z (%) 423 (59, Mþ), 277 (67), 200 (24), 146 (88), 77 (75).
1-Isopropyl-2-isopropylamino-benzo[4,5]thieno[3,2-d]-[1,2,4]
1-Butyl-2-phenyl-benzo[4,5]thieno[3,2-d][1,2,4]triazolo-[1,5-a]
1
pyrimidin-5(1H)-one (9b). H NMR (400 MHz, CDCl3) d
(ppm): 0.92 (t, J ¼ 7.0 Hz, 3H, CH3), 1.30–1.39 (m, 2H,
CH2), 1.80–1.88 (m, 2H, CH2), 4.30 (t, J ¼ 6.9 Hz, 2H,
NCH2), 7.48–8.33 (m, 9H, ArAH). IR (KBr): 1674 (C¼¼O),
1573, 1495, 745 cmꢁ1. MS: m/z (%) 374 (65, Mþ), 277 (68),
200 (24), 146 (87), 77 (83).
1
triazolo[1,5-a]pyrimidin-5(1H)-one (7k). H NMR (400 MHz,
CDCl3) d (ppm): 1.35 (d, J ¼ 7.0 Hz, 6H, 2CH3), 1.75 (d, J ¼
7.0 Hz, 6H, 2CH3), 4.05 (t, J ¼ 6.9 Hz, 1H, NCH), 4.70 (s,
1H, NCH), 7.50–8.34 (m, 4H, ArAH), 9.89 (s, 1H, NH). IR
(KBr): 3411 (NH), 1672 (C¼¼O), 1574, 1490, 741 cmꢁ1. MS:
m/z (%) 341 (34, Mþ), 277 (55), 201 (37), 146 (73), 77 (65).
1-Isopropyl-2-phenylamino-benzo[4,5]thieno[3,2-d][1,2,4]
2-Methyl-1-phenyl-benzo[4,5]thieno[3,2-d][1,2,4]triazolo-
[1,5-a]pyrimidin-5(1H)-one (9c). H NMR (400 MHz,
1
CDCl3/TFA) d (ppm): 2.42 (t, J ¼ 7.2 Hz, 3H, CH3), 7. 44 –7.
99 (m, 9H, ArAH). IR (KBr): 1671 (C¼¼O), 1571, 1491, 741
cmꢁ1. MS: m/z (%) 332 (57, Mþ), 277 (68), 201 (31), 146 (92),
77 (65).
1-Phenyl-2-phenyl-benzo[4,5]thieno[3,2-d][1,2,4]triazolo-
[1,5-a]pyrimidin-5(1H)-one (9d). H NMR (400 MHz,
CDCl3/TFA) d (ppm): 7.48–8.33 (m, 14H, ArAH). IR (KBr):
1673 (C¼¼O), 1575, 1494, 737 cmꢁ1. MS: m/z (%) 394 (100,
Mþ), 277 (64), 201 (25), 145 (73), 77 (76).
1
triazolo[1,5-a]pyrimidin-5(1H)-one (7l). H NMR (400
MHz, CDCl3/TFA) d (ppm): 1.86 (d, J ¼ 7.2 Hz, 6H, 2CH3),
4.80–4.91 (m, 1H, CH), 6.90–8.35 (m, 9H, ArAH). IR (KBr):
3416 (NH), 1672 (C¼¼O), 1577, 1493, 743 cmꢁ1. MS: m/z (%)
375 (42, Mþ), 277 (57), 201 (18), 146 (86), 77 (67).
1-Isopropyl-2-(4-methyl-phenylamino)-benzo[4,5]thieno-
1
[3,2-d][1,2,4]triazolo[1,5-a]pyrimidin-5(1H)-one (7m). H
NMR (400 MHz, CDCl3/TFA) d (ppm): 1.86 (d, J ¼ 7.0 Hz,
6H, 2CH3), 2.10 (s, 3H, ArACH3), 4.83 (d, J ¼ 6.9 Hz, 1H,
NCH), 6.97–8.37 (m, 8H, ArAH). IR (KBr): 3415 (NH), 1670
(C¼¼O), 1576, 1490, 742 cmꢁ1. MS: m/z (%) 389 (59, Mþ),
277 (77), 201 (16), 146 (92), 91 (71), 77 (86).
Acknowledgments. The authors gratefully acknowledge finan-
cial support of this work by the National Natural Science Founda-
tion of China (Project No. 20772041), the Key Project of Chinese
Ministry of Education (No. 107082), and the Doctors’ Research
Foundation of Huazhong Agricultural University (Project No.
52204-07092).
1-Butyl-2-(4-methyl-phenylamino)-benzo[4,5]thieno[3,2-d]
[1,2,4]triazolo[1,5-a]pyrimidin-5(1H)-one (7n). H NMR
1
(400 MHz, CDCl3/TFA) d (ppm): 1.02 (t, J ¼ 7.0 Hz, 3H,
CH3), 1.48–1.43 (m, 2H, CH2), 1.91–1.98 (m, 2H, CH2), 2.34
(s, 3H, ArACH3), 4.47 (t, J ¼ 6.9 Hz, 2H, NCH2), 7.22–8.43
(m, 8H, ArAH). IR (KBr): 3418 (NH), 1676 (C¼¼O), 1572,
1495, 749 cmꢁ1. MS: m/z (%) 403 (67, Mþ), 277 (69), 201
(21), 146 (80), 91 (68), 77 (79).
REFERENCES AND NOTES
[1] Walter, H. WO Pat. 9, 911, 631 (1999); Chem Abstr 1999,
130, 237580.
1-Butyl-2-(isopropylamino)-benzo[4,5]thieno[3,2-d][1,2,4]-
1
[2] Walter, H. WO Pat. 9, 914, 202 (1999); Chem Abstr 1999,
130, 252368.
triazolo[1,5-a]pyrimidin-5(1H)-one (7o). H NMR (400
MHz, CDCl3) d (ppm): 0.98 (t, J ¼ 7.0 Hz, 3H, CH3), 1.35 (t,
J ¼ 7.0 Hz, 6H, 2CH3), 1.40–1.49 (m, 2H, CH2), 1.80–1.88
(m, 2H, CH2),4.00–4.15 (m, 1H, NCH), 4.22 (t, J ¼ 6.9 Hz,
2H, NCH2), 7.55–8.33 (m, 4H, ArAH), 9.83 (s, 1H, NH). IR
(KBr): 3413 (NH), 1671 (C¼¼O), 1571, 1493, 733 cmꢁ1. MS:
m/z (%) 355 (55, Mþ), 277 (64), 200 (26), 146 (89), 77 (67).
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1
olo[1,5-a]pyrimidin-5(1H)-one (7p). H NMR (400 MHz,
CDCl3/TFA) d (ppm): 1.01 (t, J ¼ 7.0 Hz, 3H, CH3), 1.40–
1.47 (m, 2H, CH2), 1.85–1.99 (m, 2H, CH2), 4.41 (q, J ¼ 6.9
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(NH), 1675 (C¼¼O), 1576, 1492, 742 cmꢁ1. MS: m/z (%) 389
(63, Mþ), 277 (62), 201 (26), 146 (88), 77 (74).
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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S.-Z. Xu, M.-H. Cao, C.-S. Chen, and M.-W. Ding
Vol 46
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DOI 10.1002/jhet