Synthesis of novel 2-alkoxy(aralkoxy)-4H-[1,2,4]triazolo[1,5-a]quinazolin- 5-ones starting with dialkyl-N-cyanoimidocarbonates

Article abstract of DOI:10.1002/jhet.574

A novel series of 2-alkoxy(aralkoxy)-4H-[1,2,4]triazolo[1,5-a]quinazolines were synthesized employing N-cyanoimidocarbonates and 2-hydrazinobenzoic acid as building blocks. Chemical transformation of the inherent lactam moiety in the targeted 2-alkoxy(ara

Full text of DOI:10.1002/jhet.574

656
Synthesis of Novel 2-Alkoxy(aralkoxy)-4H-[1,2,4]triazolo[1,5-a]
quinazolin-5-ones Starting with Dialkyl-N-Cyanoimidocarbonates
Vol 48
Rashad Al-Salahia* and Detlef Geffkenb
aDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University,
Riyadh 11451, Saudi Arabia
bDepartment of Chemistry, Institute of Pharmacy, Hamburg University,
Hamburg 20146, Germany
*E-mail: salahi76@yahoo.com
Received May 3, 2010
DOI 10.1002/jhet.574
Published online 28 March 2011 in Wiley Online Library (wileyonlinelibrary.com).
A novel series of 2-alkoxy(aralkoxy)-4H-[1,2,4]triazolo[1,5-a]quinazolines were synthesized employ-
ing N-cyanoimidocarbonates and 2-hydrazinobenzoic acid as building blocks. Chemical transformation
of the inherent lactam moiety in the targeted 2-alkoxy(aralkoxy)[1,2,4]triazolo[1,5-a]quinazolines was
offered access to a variety of derivatives.
J. Heterocyclic Chem., 48, 656 (2011).
INTRODUCTION
and the corresponding alcohol according to an estab-
lished literature procedure was reported [7]. Based on the
high reactivity of N-cyanoimidocarbonates towards
hydrazines to produce 1,2,4-triazole derivatives [8–10],
analogously, reaction of 1 with 2 in ethanol under ice
cooling in the presence of triethylamine provided the in-
termediate 1,2,4-triazole derivative 4, which upon treat-
ment with hydrochloric acid (36%) produced the 2-
alkoxy(aralkoxy)[1,2,4]triazolo[1,5-a]quinazolin-5-ones
compounds 5a–g in 40–60% yield (Scheme 1) [11]. The
structure of the novel [1,2,4]triazolo[1,5-a]quinazolin-
Compounds with 1,2,4-triazoloquinazoline moiety
have been shown to exhibit diverse biological activities.
For example, the novel compound I is effective adeno-
sine antagonist whereas the related compound II was
found to be benzodiazepine receptor antagonist [1–4].
The recently reported 1,2,4-triazoloquinazolines of type
III were also found to exhibit promising antihistaminic
activity against histamine induced bronchospasm and
showed negligible sedation compared to chlorphenir-
amine maleate and could therefore serve as lead mole-
cules for further modification to obtain a clinically use-
ful class of non-sedative antihistamines [5,6]. In view of
the beforementioned biological activities of diverse tria-
zoloquinazolines and continuation of our ongoing stud-
ies dealing with the chemistry of N-cyanoimidocarbon-
ates and their precursors, we wish to report herein the
results of our study of cyclocondensation of N-cyanoi-
midocarbonates with hydrazinobenzoic acid to give 2-
alkoxy(aralkoxy)[1,2,4]triazolo[1,5-a]quinazolin-5-ones.
1
5-ones 5a–g was confirmed by IR, H NMR, 13C NMR
spectra, and microanalysis (see experimental). The IR
spectra of compounds 5a–g are characterized by a
strong (C¼¼O)-stretching band at 1685–1705 cmꢀ1
.
Alkylation of lactams with alkyl halides may give rise
to N- or/and O-alkylated products, the outcome of the
reaction being dependent on the pH of the reaction, tem-
perature, the nature of solvents, and the reactivity of the al-
kylating agents [12–14]. Accordingly, when the [1,2,4]tri-
azolo[1,5-a]quinazolin-5-ones 5a,b were allowed to react
with alkyl halides in a molar ratio of 1:1.5 in absolute di-
methyl formamide at room temperature in the presence of
potassium carbonate, the corresponding 4-alkyl[1,2,4]tria-
zolo[1,5-a]quinazolin-5-ones 6a–h resulted in 62–87%
yield [15]. Under these conditions, formation of the
RESULTS AND DISCUSSION
The preparation of several dialkyl N-cyanoimidocar-
bonates 1 from equimolar amounts of cyanogen bromide
C
V
2011 HeteroCorporation

May 2011
Synthesis of Novel 2-Alkoxy(aralkoxy)-4H-[1,2,4]triazolo[1,5-a]quinazolin-5-ones
Starting with Dialkyl-N-cyanoimidocarbonates
657
Scheme 1
isomeric lactim ethers was not observed (Scheme 2). The
products 6a–h were obtained as colored solid compounds
and their IR spectra display a strong (C¼¼O)-absorption
band at 1670–1685 cmꢀ1. Treatment of compounds
5a,b,e,f,g with lithium aluminum hydride in absolute tetra-
hydrofuran at room temperature furnished the aimed 4,5-
dihydro[1,2,4]triazolo[1,5-a] quinazolines 7a–e in 45–
70% yield [16]. The compounds 7a–e were obtained after
column chromatography as colorless solids, and their
structure was verified by elemental analyses and spectral
(NMR, MS, and IR) data. The IR revealed the disappear-
ance of a (C¼¼O) absorption band at 1685–1705 cmꢀ1
(previously found in compound 5) confirmed the forma-
tion of the products 7. When equimolar amounts of
[1,2,4]triazolo[1,5-a] quinazolin-5-ones 5a,b,e,f,g and
phosphorus pentasulfide were allowed to react in absolute
pyridine under reflux for 2 h, the targeted 2-alkoxy(aral-
koxy)-4H-[1,2,4]triazolo[1,5-a]quinazolin-5-thiones 8a–e
could be isolated in excellent yields of 85–97% as yellow
solids [17]. In the IR spectra, the compounds 8a–e dis-
played a weak absorption band of a (C¼¼S) around 1244–
Scheme 2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

658
R. Al-Salahi and D. Geffken
Vol 48
1257 cmꢀ1, and the 13C NMR spectra are characterized by
a (C¼¼S) resonance at 184.9–185.6 ppm. Reaction of the
[1,2,4]triazolo[1,5-a]quinazolin-5-thiones 8a,d with dif-
ferent alkyl halides in aqueous 0.5 M sodium hydroxide
solution afforded smoothly the expected thioethers 9a–d
in 58–73% yield [18]. Conversion of [1,2,4]triazoloqui-
nazolin-5-ones 5 into 5-chloro-[1,2,4]triazolo[1,5-a] qui-
nazolines 10 has been successfully achieved by chlorina-
tion with either oxalyl chloride in boiling 1,1,2-trichloro-
ethane for 19 h [10] or with phosphorus oxychloride in
boiling benzene for 2 h, followed by titration with a satu-
rated aqueous solution of potassium carbonate [19].
Although both methods gave acceptable yields, the reac-
tion of 5 with phosphorus oxychloride is more advanta-
geous with regard to short reaction time and higher yields.
The formation of 10 was accompanied by the gradual dis-
appearance of the characteristic (C¼¼O) band of 5 at
1685–1705 cmꢀ1. Hydrogenolysis of 5f on Pd/C in tetra-
hydrofuran cleanly afforded 1,2,4,5-tetrahydro[1,2,4]tria-
zolo[1,5-a]quinazolin-2,5-dione 11 as a colorless solid in
excellent yield of 95% and its structure was followed
unambiguously from IR spectrum which showed two
(CArom), 147.87 (C-guanidine), 159.93 (C¼¼O), 168.26 (C-iso-
urea). ms: m/z (%): 216 (Mþ, 100), 201 (Mþ-methyl, 15), 187
(30), 145 (27), 104 (17). Anal. Calcd. for C10H8N4O2
(216.20): C, 55.56; H, 3.73; N, 25.91. Found: C, 55.38; H,
3.83; N, 25.99.
2-Ethoxy-4H-[1,2,4]triazolo[1,5-a]quinazolin-5-one (5b). Yellow
solid; (yield: 60%), m.p. 244ꢁC (THF). IR (KBr) 1689 cmꢀ1
.
1H NMR (DMSO-d6): dH 1.38 (t, J ¼ 7.07 Hz, 3H, CH3), 4.35
(q, J ¼ 14.13 Hz, 2H, CH2), 7.47–8.16 (m, 4H, ArH), 13.01
(s, 1H, NH); 13C NMR (DMSO-d6): dC 14.86 (CH3), 65.64
(CH2), 114.26, 116.79, 125.50, 128.59, 135.75, 136.12 (CArom),
147.74 (C-guanidine), 159.92 (C¼¼O), 167.56 (C-isourea). ms:
m/z (%): 230 (Mþ, 95), 201 (Mþ-ethyl, 90), 187 (7), 160 (4),
134 (100), 104 (25). Anal. Calcd. for C11H10N4O2 (230.23): C,
57.39; H, 4.38; N, 24.34. Found: C, 57.18; H, 4.49; N, 24.40.
2-Isopropoxy-4H-[1,2,4]triazolo[1,5-a]quinazolin-5-one
(5c). Pale brown solid; (yield: 40%), m.p. 221ꢁC (THF). IR
1
(KBr) 1691 cmꢀ1. H NMR (DMSO-d6): dH 1.37 (d, J ¼ 7.35
Hz, 6H, ACH( CH3)2), 4.95–5.02 (m, 1H, CH( CH3)2), 6.96–
8.16 (m, 4H, ArH), 11.34 (s, 1H, NH); 13C NMR (DMSO-d6):
dC 22.16 (CH3), 73.10 (CH), 114.25, 116.83, 125.46, 128.61,
135.73, 136.64 (CArom), 147.60 (C-guanidine), 158.85 (C¼¼O),
167.47 (C-isourea). ms: m/z (%): 244 (Mþ, 35), 202 (Mþ-iso-
propyl, 100), 160 (7), 134 (80), 105 (40), 77 (30). Anal. Calcd.
for C12H12N4O2 (244.26): C, 59.01; H, 4.95; N, 22.94. Found:
C, 59.37; H, 4.88; N, 22.55.
(C¼¼O) absorption bands at 1707 and 1686 cmꢀ1
.
2-Pentyloxy-4H-[1,2,4]triazolo[1,5-a]quinazolin-5-one (5d). Ye-
llow solid; (yield: 50%), m.p. 234ꢁC (THF). IR (KBr) 1692
EXPERIMENTAL
cmꢀ1
.
1H NMR (DMSO-d6): dH 0.91 (t, J ¼ 7.41 Hz, 3H,
ACH2CH2CH2CH2CH3), 1.33–1.42 (m, 4H, ACH2CH2CH2
CH2CH3), 1.73–1.79 (m, 2H, ACH2CH2CH2CH2CH3), 4.30
(t, J ¼ 7.60 Hz, 2H, ACH2CH2CH2CH2CH3), 7.45–8.16 (m,
4H, ArH), 12.98 (s, 1H, NH); 13C NMR (DMSO-d6): dC 14.27
(ACH2CH2CH2CH2CH3), 22.14 (ACH2CH2CH2CH2CH3),
27.63 (ACH2CH2CH2CH2CH3), 28.47 (CH2CH2CH2CH2
CH3), 69.74 (ACH2CH2CH2CH2CH3), 114.21, 116.80,
125.45, 128.6, 135.72, 136.11 (CArom), 147.74 (C-guanidine),
159.91 (C¼¼O), 167.70 (C-isourea). ms: m/z (%): 272 (Mþ,
15), 202 (Mþ-pentyl, 100), 160 (5), 134 (60), 104 (15), 43
(67). Anal. Calcd. for C14H16N4O2 (272.31): C, 61.75; H,
5.92; N, 20.57. Found: C, 61.68; H, 6.02; N, 20.52.
Melting points were determined on open glass capillaries
using a Mettler FP 62 apparatus and are uncorrected. Elemen-
tal analyses were carried out with a Heraeus CHN-O-Rapid
Instrument. The IR (KBr) spectra were recorded on a Shi-
1
madzu FTIR 8300. H NMR (400.1 MHz) and 13C NMR spec-
tra were recorded on a Bruker AMX 400 spectrometer and
chemical shifts are giving in a (ppm) downfield from tetrame-
thylsilane (TMS) as an internal standard, DMSO is using as
solvent. Mass spectra were recorded on a Finnigan MAT 311A
and on a VG 70-250S (VG Analytical) instrument. Follow-up
of the reactions and checking the purity of compounds was
made by TLC on DC-Mikrokarten polygram SIL G/UV254
from the Macherey-Nagel Firm, Duren Thickness: 0.25 m.
,
2-Allyloxy-4H-[1,2,4]triazolo[1,5-a]quinazolin-5-one (5e). Ye-
llow solid; (yield: 55%), m.p. 215ꢁC (THF). IR (KBr) 1696
Column chromatography was conducted on silica gel (ICN
˚
Silica 100–200, active 60 A).
cmꢀ1
.
1H NMR (DMSO-d6): dH 4.86 (d, J ¼ 5.68 Hz, 2H,
ACH2¼¼CHCH2), 5.42–5.65 (m, 2H, ACH2¼¼CHCH2), 6.05–
6.15 (m, 1H, ACH2¼¼CHCH2), 7.48–8.17 (m, 4H, ArH), 13.01
(s, 1H, NH); 13C NMR (DMSO-d6): dC 69.60 (ACH2¼¼
CHCH2), 113.82 (ACH2¼¼CHCH2), 116.44, 118.25, 125.16,
128.13 (CArom), 134.11 (ACH2¼¼CHCH2), 135.30, 135.62
(CArom), 147.30 (C-guanidine), 159.45 (C¼¼O), 166.92 (C-iso-
urea). ms: m/z (%): 242 (Mþ, 100), 202 (Mþ-allyl, 23), 187
(9), 160 (5), 134 (18), 104 (37), 41 (40). Anal. Calcd. for
C12H10N4O2 (242.24): C, 59.50; H, 4.16; N, 23.13. Found: C,
59.20; H, 4.42; N, 22.85.
2-Alkoxy(aralkoxy)-4H-[1,2,4]triazolo[1,5-a]quinazolin-5-
ones (5a–g). General procedure. 10 mmol of 2-hydrazino-
benzoic acid 2 was added portion wise to a stirred solution of
1 (10 mmol) in EtOH (20 mL) at 0ꢁC. Afterwards, triethyl-
amine (30 mmol) was added drop-wise over a period of 30
min. After the addition was complete, the reaction mixture
was left to stirr overnight at room temperature. Acidification
of the mixture was performed by conc. HCl under ice cooling
followed by refluxing for 1–3 h. After cooling, the mixture
was poured into ice/water, the resulting solid was filtered,
washed with water and dried. Recrystallization from THF gave
analytically pure colored 5a–g.
2-Benzyloxy-4H-[1,2,4]triazolo[1,5-a]quinazolin-5-one
(5f). White solid; (yield: 58%), m.p. 258ꢁC (THF). IR (KBr)
1
1701 cmꢀ1. H NMR (DMSO-d6): dH 5.39 (s, 2H, CH2), 7.37–
2-Methoxy-4H-[1,2,4]triazolo[1,5-a]quinazolin-5-one (5a). Ye-
llow solid; (yield: 60%), m.p. 228ꢁC (THF). IR (KBr) 1685
8.16 (m, 9H, ArH), 13.04 (s, 1H, NH); 13C NMR (DMSO-d6):
dC 71.18 (CH2), 114.34, 116.81, 125.53, 127.74, 128.03,
128.85, 135.75, 136.11, 136.77 (CArom), 147.11 (C-guanidine),
160.40 (C¼¼O), 167.17 (C-isourea). ms: m/z (%): 292 (Mþ,
1
cmꢀ1. H NMR (DMSO-d6): dH 3.99 (s, 3H, CH3), 7.48–8.15
(m, 4H, ArH), 13.15 (s, 1H, NH), 13C NMR (DMSO-d6): dC
57.16 (CH3), 114.25, 116.83, 125.50, 128.58, 135.72, 136.12
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

May 2011
Synthesis of Novel 2-Alkoxy(aralkoxy)-4H-[1,2,4]triazolo[1,5-a]quinazolin-5-ones
Starting with Dialkyl-N-cyanoimidocarbonates
659
35), 250 (6), 248 (17), 201(12), 91(100). Anal. Calcd. for
C16H12N4O2 (292.30): C, 65.75; H, 4.14; N, 19.17. Found: C,
65.39; H, 4.04; N,19.06.
3H, NCH2CH3), 4.24 (q, J ¼ 14.31 Hz, 2H, NCH2CH3), 4.11
(s, 3H, OCH3), 7.58–8.29 (m, 4H, ArH); 13C NMR (DMSO-
d6): dC 12.81 (NCH2CH3), 52.34 (NCH2CH3), 57.18 (OCH3),
114.13, 116.22, 125.71, 128.79, 135.20, 135.42 (CArom),
148.49 (C-guanidine), 158.64 (C¼¼O), 167.99 (C-isourea). ms:
m/z (%): 244 (Mþ, 67), 230 (Mþ-methyl, 35), 216 (87), 91
(22). Anal. Calcd. for C12H12N4O2 (244.26): C, 59.01; H,
4.95; N, 22.94. Found: C, 58.79; H, 5.04; N, 22.58.
2-Phenethyloxy-4H-[1,2,4]triazolo[1,5-a]quinazolin-5-one
(5g). White solid; (yield: 56%), m.p. 227ꢁC (THF). IR (KBr)
1705 cmꢀ1
2H, AOCH2CH2Ph), 4.50 (t,
.
1H NMR (DMSO-d6): dH 3.20 (t, J ¼ 7.50 Hz,
J
¼
7.51 Hz, 2H,
AOCH2CH2Ph), 7.20–8.19 (m, 9H, ArH), 13.75 (s, 1H, NH);
13C NMR (DMSO-d6): dC 34.94 (AOCH2CH2Ph), 70.23
(AOCH2CH2Ph), 116.81, 114.32, 126.80, 125.51, 128.59,
128.74, 129.37, 136.14, 138.33 (CArom), 147.72 (C-guanidine),
159.91 (C¼¼O), 167.57 (C-isourea). ms: m/z (%): 306 (Mþ,
53), 292 (MþACH2, 15), 202 (Mþ-phenethyl, 80), 134 (15),
105 (100), 91 (28). Anal. Calcd. for C17H14N4O2 (306.33): C,
66.66; H, 4.61; N, 18.29. Found: C, 66.32; H, 4.94; N, 18.33.
2-Alkoxy(aralkoxy)-4-alkyl(aralkyl)-4H-[1,2,4]triazolo[1,5-
a]quinazolin-5-ones (6a–h). General procedure. To a solu-
tion of 5a,b (1 mmol) in DMF (5 mL) was added potassium
carbonate (1.2 mmol) portion wise over a period of 10 min at
room temperature. After stirring for 20 min, the appropriate
alkyl halide (1.5 mmol) was added drop wise, and the reaction
mixture was stirred for 18 h at room temperature. The mixture
was poured into ice/water, the precipitate was filtered off,
washed with water and dried. Analytically pure products 6a–h
were obtained after recrystallization from THF.
4-Allyl-2-methoxy-4H-[1,2,4]triazolo[1,5-a]quinazolin-5-one
(6e). Yellow solid; (yield: 82%), m.p. 132ꢁC (THF). IR (KBr)
1
1680 cmꢀ1. H NMR (DMSO-d6): dH 4.13 (s, 3H, CH3), 4.83
(d, J ¼ 4.60 Hz, 2H, ACH2¼¼CHCH2), 5.30–5.42 (m, 2H,
ACH2¼¼CHCH2), 6.04–6.30 (m, 1H, ACH2¼¼CHCH2), 7.46–
8.31 (m, 4H, ArH); 13C NMR (DMSO-d6): dC 45.53
(ACH2¼¼CHCH2), 57.14 (CH3), 114.47 (CArom), 116.10
(ACH2¼¼CHCH2), 117.18, 125.83, 128.82, 131.66 (CArom),
135.42 (ACH2¼¼CHCH2), 135.86 (CArom), 148.79 (C-guani-
dine), 157.81 (C¼¼O), 168.43 (C-isourea). ms: m/z (%): 256
(Mþ, 70), 216 (100), 187 (11), 160 (5), 104 (42), 41 (53).
Anal. Calcd. for C13H12N4O2 (256.27): C, 60.93; H, 4.72; N,
21.86. Found: C, 60.79; H, 5.01; N, 21.76.
2-Ethoxy-4-prop-2-ynyl-4H-[1,2,4]triazolo[1,5-a]quinazolin-
5-one (6f). White solid; (yield: 87%), m.p. 147ꢁC (THF). IR
1
(KBr) 1685 cmꢀ1. H NMR (DMSO-d6): dH 1.64 (t, J ¼ 7.26
Hz, 3H, OCH2CH3), 3.58 (s, 1H, HCBCCH2), 4.64 (q, J ¼
14.32 Hz, 2H, OCH2CH3), 5.10 (s, 2H, HCBCCH2), 7.77–8.48
(m, 4H, ArH); 13C NMR (DMSO-d6): dC 14.18 (CH3), 32.99
(HCBCCH2), 65.77 (OCH2), 74.88 (HCBCCH2), 78.13
(HCBCCH2), 122.45, 125.83, 129.68, 131.61(CArom), 148.46
(C-guanidine), 163.58 (C¼¼O), 167.53 (C-isourea). ms: m/z
(%): 268 (Mþ, 78), 253 (12), 239 (10), 197 (80), 169 (12),
145 (13), 107 (25), 39 (100). Anal. Calcd. for C14H12N4O2
(268.28): C, 62.68; H, 4.51; N, 20.88. Found: C, 62.45; H,
4.75; N, 21.08.
4-(4-Bromobenzyl)-2-methoxy-4H-[1,2,4]triazolo[1,5-a]qui-
nazolin-5-one (6a). Yellow solid; (yield: 83%), m.p. 194ꢁC
(THF). IR (KBr) 1676 cmꢀ1 1H NMR (DMSO-d6): dH 4.12
.
(s, 3H, CH3), 5.37 (s, 2H, CH2), 7.50–8.33 (m, 8H, ArH); 13C
NMR (DMSO-d6): dC 46.21 (CH2), 57.23 (CH3), 114.28,
116.13, 118.45, 121.03, 125.88, 128.96, 130.50, 131.68,
135.65, 136.02 (CArom), 148.80 (C-guanidine), 159.02 (C¼¼O),
167.84 (C-isourea). ms: m/z (%): 385 (Mþ, 100), 355 (10),
305 (13), 201 (70), 171 (90), 90 (30). Anal. Calcd. for
C17H13BrN4O2 (385.22): C, 53.01; H, 3.40; N, 14.54. Found:
C, 52.78; H, 3.47; N, 14.43.
4-Cyclopropylmethyl-2-ethoxy-4H-[1,2,4]triazolo[1,5-a]qui-
nazolin-5-one (6g). White solid; (yield: 70%), m.p. 116ꢁC
(THF). IR (KBr) 1677 cmꢀ1 1H NMR (DMSO-d6): dH 0.63–
.
2-Methoxy-4-phenethyl-4H-[1,2,4]triazolo[1,5-a]quinazolin-
5-one (6b). White solid; (yield: 85%), m.p. 155ꢁC (THF). IR
0.69 (m, 5H, ACH2C3H5), 1.56 (t, J ¼ 7.12 Hz, 3H, CH3), 4.17
(s, 2H, ACH2C3H5), 4.47 (q, J ¼ 14.34 Hz, 2H, OCH2), 7.68–
8.38 (m, 4H, ArH); 13C NMR (DMSO-d6): dC 3.93 (2C-cyclo-
propyl), 9.81 (C-cyclopropyl), 14.85 (CH3), 48.37 (ACH2C3H5),
65.80 (OCH2), 114.17, 116.23, 125.85, 128.93, 135.43, 135.97
(CArom), 148.78 (C-guanidine), 158.94 (C¼¼O), 167.20 (C-iso-
urea). ms: m/z (%): 284 (Mþ, 76), 256 (13), 230 (28), 145 (34),
104 (11), 91 (88). Anal. Calcd. for C15H16N4O2 (284.32): C,
63.37; H, 5.67; N, 19.71. Found: C, 63.55; H, 5.74; N, 19.50.
4-(2,4-Dichlorobenzyl)-2-ethoxy-4H-[1,2,4]triazolo[1,5-a]qui-
nazolin-5-one (6h). White solid; (yield: 73%), m.p. 203ꢁC
1
(KBr) 1675 cmꢀ1. H NMR (DMSO-d6): dH 3.04 (t, J ¼ 7.54
Hz, 2H, ANCH2CH2Ph), 4.02 (s, 3H, OCH3), 4.31 (t, J ¼
7.51 Hz, 2H, ANCH2CH2Ph), 7.22–8.20 (m, 9H, ArH); 13C
NMR (DMSO-d6): dC 33.08 (ANCH2CH2Ph), 44.66
(ANCH2CH2Ph), 57.21(OCH3), 114.18, 116.11, 125.82,
126.88, 128.87, 135.42, 135.84, 138.39 (CArom), 148.59 (C-
guanidine), 158.76 (C¼¼O), 167.97 (C-isourea). ms: m/z (%):
320 (Mþ, 90), 229 (70), 216 (100), 188 (15), 160 (11), 145
(12), 104 (40). Anal. Calcd. for C18H16N4O2 (320.35): C,
67.49; H, 5.03; N, 17.49. Found: C, 67.49; H, 5.15; N, 17.18.
4-Benzyl-2-methoxy-4H-[1,2,4]triazolo[1,5-a]quinazolin-5-
one (6c). Yellow solid; (yield: 82%), m.p. 134ꢁC (THF). IR
1
(THF). IR (KBr) 1676 cmꢀ1. H NMR (DMSO-d6): dH 1.63 (t,
J ¼7.02 Hz, 3H, CH3), 4.61 (q, J ¼ 14.02 Hz, 2H, CH2), 5.31
(s, 2H, CH2Ph), 7.31–8.19 (m, 7H, ArH); 13C NMR (DMSO-
d6): dC 14.73 (CH3), 44.96 (CH2Ph), 65.80 (CH2), 114.34,
116.1, 125.81, 127.83, 129.01, 129.70, 131.62, 132.40, 133.15,
135.83, 136.17 (CArom), 148.63 (C-guanidine), 159.27 (C¼¼O),
167.19 (C-isourea). ms: m/z (%): 390 (Mþþ1, 18), 389 (Mþ,
54), 230 (23), 187 (5), 143 (12), 90 (58). Anal. Calcd. for
C18H14Cl2N4O2 (389.24): C, 55.54; H, 3.63; N, 14.39. Found:
C, 55.17; H, 3.75; N, 14.37.
(KBr) 1678 cmꢀ1 1H NMR (DMSO-d6): dH 4.13 (s, 3H,
.
CH3), 5.34 (s, 2H, CH2), 7.50–8.30 (m, 9H, ArH); 13C NMR
(DMSO-d6): dC 46.75 (CH2), 57.21(CH3), 114.24, 116.86,
117.79, 125.80, 128.89, 129.11, 131.66, 132.45, 135.86,
135.52 (CArom), 148.85 (C-guanidine), 158.96 (C¼¼O), 167.86
(C-isourea). ms: m/z (%): 306 (Mþ, 100), 277 (8), 262 (5),
201 (22), 91 (55). Anal. Calcd. for C17H14N4O2 (306.33): C,
66.66; H, 4.61; N, 18.29. Found: C, 66.46; H, 4.69; N, 17.93.
4-Ethyl-2-methoxy-4H-[1,2,4]triazolo[1,5-a]quinazolin-5-one
(6d). White solid; (yield: 62%), m.p. 135ꢁC (THF). IR (KBr)
2-Alkoxy(aralkoxy)-4,5-dihydro[1,2,4]triazolo[1,5-a]quina-
zolines (7a–e). General procedure. A solution of 5 (1 mmol)
in dry THF (5 mL) was added drop wise to a stirred
1672 cmꢀ1
.
1H NMR (DMSO-d6): dH 1.37 (t, J ¼ 7.04 Hz,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

660
R. Al-Salahi and D. Geffken
Vol 48
suspension of LiAlH4 (3 mmol) in dry THF (10 mL). After
stirring at room temperature for 3 h, water (0.4 mL) was added
carefully and the mixture was stirred for an additional 30 min.
The reaction mixture was filtered and the solvent removed
under reduced pressure, the residue was dissolved in THF and
passed through a short column chromatography, the solvent
was removed under reduced pressure, and the obtained solid
was recrystallized from EtOAc/n-hexane.
4,5-Dihydro-2-methoxy[1,2,4]triazolo[1,5-a]quinazoline
(7a). White solid; (yield: 60%), m.p. 133ꢁC (EtOAc-hexane).
1H NMR (DMSO-d6): dH 3.90 (s, 3H, CH3), 4.20 (s, 2H, CH2-
quinazoline), 7.28–7.82 (m, 4H, ArH), 7.95 (s, 1H, NH); 13C
NMR (DMSO-d6): dC 43,22 (CH2-quinazoline), 56.35 (OCH3),
112.72, 119.64, 124.50, 126.23, 130.75, 134.16 (CArom),
155.18 (C-guanidine), 165.29 (C-isourea). ms: m/z (%): 201
(Mþ-1, 100), 186 (14), 143 (5), 129 (11), 89 (9). Anal. Calcd.
for C10H10N4O (202.22): C, 59.40; H, 4.98; N, 27.71. Found:
C, 59.15; H, 5.18; N, 27.38.
4,5-Dihydro-2-ethoxy[1,2,4]triazolo[1,5-a]quinazoline
(7b). White solid; (yield: 61%), m.p. 142ꢁC (EtOAc-hexane).
1H NMR (DMSO-d6): dH 1.31 (t, J ¼ 7.21 Hz, 3H, CH3), 4.24
(q, J ¼ 14.40 Hz, 2H, CH2), 4.49 (s, 2H, CH2-quinazoline),
7.08–7.33 (m, 4H, ArH), 7.76 (s, 1H, NH); 13C NMR (DMSO-
d6): dC 14.94 (CH3), 42.38 (CH2-quinazoline), 64.71 (OCH2),
112.71, 119.70, 124.52, 126.79, 128.79, 134.14 (CArom),
154.99 (C-guanidine), 167.37 (C-isourea). ms: m/z (%): 216
(Mþ, 100), 187 (8), 145 (13), 104 (11), 76 (18). Anal. Calcd.
for C11H12N4O (216.24): C, 61.10; H, 5.59; N, 25.91. Found:
C, 60.86; H, 5.57; N, 25.63.
145 (6), 105 (35). Anal. Calcd. for C17H16N4O (292.34): C,
69.85; H, 5.52; N, 19.16. Found: C, 69.51; H, 5.56; N, 18.93.
2-Alkoxy(aralkoxy)-4H-[1,2,4]triazolo[1,5-a]quinazolin-5-
thiones (8a–e). General procedure. Compound 5 (1 mmol)
was refluxed with phosphorus pentasulfide (1 mmol) in abso-
lute pyridine (5 mL) for 2 h. Afterwards the reaction mixture
was cooled and poured into ice/water, the yellow precipitate
was separated by filtration and washed thoroughly with water.
Recrystallization from aqueous DMF furnished analytically
pure 8a–e.
2-Methoxy-4H-[1,2,4]triazolo[1,5-a]quinazolin-5-thione
(8a). Yellow solid; (yield: 85%), m.p. 230ꢁC (DMF). IR
(KBr) 1250 cmꢀ1 1H NMR (DMSO-d6): dH 4.02 (s, 3H,
.
CH3), 7.52–7.96 (m, 4H, ArH), 14.72 (s, 1H, NH); 13C NMR
(DMSO-d6): dC 56.84 (CH3), 114.21, 122.43, 125.83, 131.77,
132.41, 135.88 (CArom), 149.59 (C-guanidine), 162.78 (C-iso-
urea), 185.01(C¼¼S). ms: m/z (%): 232 (Mþ, 100), 216 (40),
203 (4), 175 (7), 120 (23), 102 (13). Anal. Calcd. for
C10H8N4OS (232.27): C, 51.71; H, 3.47; N, 24.12; S, 13.80.
Found: C, 51.99; H, 3.22; N, 4.52; S,13.65.
2-Ethoxy-4H-[1,2,4]triazolo[1,5-a]quinazolin-5-thione
(8b). Yellow solid; (yield: 92%), m.p. 226ꢁC (DMF). IR
1
(KBr) 1248 cmꢀ1. H NMR (DMSO-d6): dH 1.39 (t, J ¼ 7.28
Hz, 3H, CH3), 4.40 (q, J ¼ 14.20 Hz, 2H, CH2), 7.51–8.62
(m, 4H, ArH), 14.70 (s, 1H, NH); 13C NMR (DMSO-d6): dC
14.39 (CH3), 65.46 (CH2), 114.20, 122.90, 125.79, 131.39,
132.39 (CArom), 145.63 (C-guanidine), 162.12 (C-isourea),
184.94 (C¼¼S). ms: m/z (%): 246 (Mþ,100), 230 (10), 218
(45), 202 (8), 150 (42). Anal. Calcd. for C11H10N4OS
(246.29): C, 53.64; H, 4.09; N, 22.75; S, 13.02. Found: C,
53.42; H, 3.87; N, 22.32; S, 13.17.
2-Allyloxy-4,5-dihydro[1,2,4]triazolo[1,5-a]quinazoline
(7c). White solid; (yield: 55%), m.p. 105ꢁC (EtOAc-hexane).
2-Allyloxy-4H-[1,2,4]triazolo[1,5-a]quinazolin-5-thione
(8c)? Yellow solid; (yield: 95%), m.p. 190ꢁC (DMF). IR
1H NMR (DMSO-d6): dH 4.76 (d,
J
¼
6.76 Hz, 2H,
ACH2¼¼CHCH2), 4.92 (s, 2H, CH2-quinazoline), 5.32–5.43
(m, 2H, ACH2¼¼CHCH2), 6.09–6.16 (m, 1H, ACH2¼¼CHCH2),
7.48–8.10 (m, 4H, ArH), 8.25 (s, 1H, NH); 13C NMR (DMSO-
d6): dC 69.63 (CH2-quinazoline), 113.87 (ACH2¼¼CHCH2),
116.45 (ACH2¼¼CHCH2), 118.20, 119.24, 125.33, 128.12,
134.57 (CArom), 135.20 (ACH2¼¼CHCH2), 135.52 (CArom),
159.37 (C-guanidine), 166.70 (C-isourea). ms: m/z (%): 228
(Mþ, 100), 209 (3), 187 (85), 116 (25). Anal. Calcd. for
C12H12N4O (228.26) : C, 63.15; H, 5.30; N, 24.55. Found: C,
63.43; H, 5.23; N, 24.42.
1
(KBr) 1244 cmꢀ1. H NMR (DMSO-d6): dH 4.85 (d, J ¼ 6.36
Hz, 2H, ACH2¼¼CHCH2), 5.31–5.46 (m, 2H, ACH2¼¼CHCH2),
6.08–6.15 (m, 1H, ACH2¼¼CHCH2), 7.48–8.62 (m, 4H, ArH),
14.72 (s, 1H, NH); 13C NMR (DMSO-d6): dC 69.92
(ACH2¼¼CHCH2), 114.27 (CArom), 118.39 (ACH2¼¼CHCH2),
122.53, 125.92, 128.21, 131.83 (CArom), 132.42 (ACH2¼¼
CHCH2), 135.92 (CArom), 145.75 (C-guanidine), 167.31 (C-iso-
urea), 185.08 (C¼¼S). ms: m/z (%): 258 (Mþ, 94), 242 (25),
216 (20), 150 (11), 120 (15). Anal. Calcd. for C12H10N4OS
(258.30): C, 55.80; H, 3.90; N, 21.69; S, 12.41. Found: C,
55.65; H, 3.97; N, 21.73; S, 12.18.
2-Benzyloxy-4,5-dihydro[1,2,4]triazolo[1,5-a]quinazoline
(7d). White solid; (yield: 70%), m.p. 158ꢁC (EtOAc-hexane).
1H NMR (DMSO-d6): dH 4.50 (s, 2H, CH2-quinazoline), 5.26
(s, 2H, OCH2Ph), 7.11–7.46 (m, 9H, ArH), 7.81 (s, 1H, NH);
13C NMR (DMSO-d6): dC 69.94 (OCH2Ph), 112.27, 119.23,
124.10, 126.30, 127.02, 127.95, 128.27, 128.95, 133.67,
136.40 (CArom), 154.55 (C-guanidine), 166.87 (C-isourea). ms:
m/z (%): 278 (Mþ, 100), 233 (7), 201 (6), 187 (18), 91 (100).
Anal. Calcd. for C16H14N4O (278.32): C, 69.05; H, 5.07; N,
20.13. Found: C, 69.35; H, 5.10; N,19.83.
2-Benzyloxy-4H-[1,2,4]triazolo[1,5-a]quinazolin-5-thione
(8d). Yellow solid; (yield: 97%), m.p. 210ꢁC (DMF). IR
(KBr) 1253 cmꢀ1 1H NMR (DMSO-d6): dH 5.42 (s, 2H,
.
CH2), 7.37–8.62 (m, 9H, ArH), 14.74 (s, 1H, NH); 13C NMR
(DMSO-d6): dC 70.60 (CH2), 114.24, 122.40, 125.37, 128.06,
128.10, 128.90, 131.72, 132.33, 135.38 (CArom), 145.90 (C-
guanidine), 167.34 (C-isourea), 185.62 (C¼¼S). ms: m/z (%):
308 (Mþ, 25), 275 (10), 218 (100), 186 (13), 150 (45), 91
(60). Anal. Calcd. for C16H12N4OS (308.36): C, 62.32; H,
3.92; N, 18.17; S, 10.40. Found: C, 61.96; H, 4.05; N, 17.87;
S,10.06.
4,5-Dihydro-2-phenethyloxy[1,2,4]triazolo[1,5-a]quinazoline
(7e). White solid; (yield: 64%), m.p. 119ꢁC (EtOAc-hexane).
1H NMR (DMSO-d6): dH 3.04 (t,
J
¼
7.40 Hz, 2H,
2-Phenethyloxy-4H-[1,2,4]triazolo[1,5-a]quinazolin-5-thione
(8e). Yellow solid; (yield: 89%), m.p. 221ꢁC (DMF). IR (KBr)
OCH2CH2Ph), 4.39 (t, J ¼ 7.51 Hz, 2H, OCH2CH2Ph), 4.48
(s, 2H, CH2-quinazoline), 7.10–7.32 (m, 9H, ArH), 7.77 (s,
1H, NH); 13C NMR (DMSO-d6): dC 34.90 (OCH2CH2Ph),
68.95 (OCH2CH2Ph), 113.33, 119.27, 126.80, 128.51, 129.37,
135.74, 136.11, 138.33 (CArom), 154.90 (C-guanidine), 166.85
(C-isourea). ms: m/z (%): 292 (Mþ, 39), 188 (100), 173 (5),
1257 cmꢀ1
.
1H NMR (DMSO-d6): dH 3.11 (t, J ¼ 6.35 Hz,
2H, OCH2CH2Ph), 4.55 (t, J ¼ 6.63 Hz, 2H, OCH2CH2Ph),
7.24–8.61 (m, 9H, ArH), 14.70 (s, 1H, NH); 13C NMR
(DMSO-d6): dC 34.45 (OCH2CH2Ph), 69.72 (OCH2CH2Ph),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

May 2011
Synthesis of Novel 2-Alkoxy(aralkoxy)-4H-[1,2,4]triazolo[1,5-a]quinazolin-5-ones
Starting with Dialkyl-N-cyanoimidocarbonates
661
114.23, 122.42, 125.00, 125.82, 126.30, 128.28, 128.85,
131.76, 135.83, 137.80 (CArom), 145.63 (C-guanidine), 165.20
(C-isourea), 184.91 (C¼¼S). ms: m/z (%): 322 (Mþ, 78), 218
(31), 187 (11) 134 (15), 91 (28). Anal. Calcd. for C17H14N4OS
(322.39): C, 63.34; H, 4.38; N, 17.38; S, 9.95. Found: C,
62.95; H, 4.65; N, 17.02; S,10.03.
2-Alkoxy(aralkoxy)-5-alkyl(aralkyl)sulfanyl[1,2,4]triazolo[1,
5-a]quina-zolines (9a–d). General procedure. Compound 8a,d
(1 mmol) was dissolved in aqueous 0.5 M sodium hydroxide
solution (10 mL), alkyl halide (1.5 mmol) was added drop
wise over a period 2 min, the mixture was left to stirr for 5–
20 min at room temperature, and the obtained solid was sepa-
rated by filtration, washed thoroughly with water and dried.
Recrystallization of the crude products from EtOH afforded
9a–d as colored pure solids.
cooled and MeOH (0.2 mL) was added drop wise, the obtained
solid was filtered, washed with hexane, dried and recrystallized
from THF-hexane.
Method-B: Compound 5 (1 mmol) was refluxed with Phos-
phorus oxychloride (1 mL) in benzene (7 mL) for 2 h. The
solvent was evaporated and the residue was treated with satu-
rated aqueous solution of potassium carbonate. The solid was
filtered, washed thoroughly with water, dried and recrystallized
from THF-hexane.
5-Chloro-2-methoxy[1,2,4]triazolo[1,5-a]quinazoline (10a).
White solid; (yield: 80%), m.p. 148ꢁC (THF-hexane). 1H
NMR (DMSO-d6): dH 3.99 (s, 3H, CH3), 7.48–8.15 (m, 4H,
ArH); 13C NMR (DMSO-d6): dC 57.16 (CH3), 114.20, 116.83,
125.51, 128.57, 135.74, 136.19 (CArom), 141.11 (C-guanidine),
159.90 (CACl), 168.26 (C-isourea). ms: m/z (%): 234 (Mþ,
100), 216 (50), 169 (40), 128 (10), 102 (15). Anal. Calcd. for
C10H7ClN4O (234.65): C, 51.19; H, 3.01; N, 23.88. Found: C,
51.12; H, 3.18; N, 23.98.
5-Chloro-2-ethoxy[1,2,4]triazolo[1,5-a]quinazoline (10b).
White solid; (yield: 89%), m.p. 134ꢁC (THF-hexane). 1H
NMR (DMSO-d6): dH 1.37 (t, J ¼ 7.07 Hz, 3H, CH3), 4.34 (q,
J ¼ 14.13 Hz, 2H, CH2), 7.49–8.15 (m, 4H, ArH); 13C NMR
(DMSO-d6): dC 14.83 (CH3), 65.67 (CH2), 114.17, 116.75,
125.52, 128.80, 135.18, 136.13 (CArom), 142.20 (C-guanidine),
159.92 (CACl), 167.38 (C-isourea). ms: m/z (%): 248 (Mþ,
78), 220 (32), 201 (4), 128 (12), 91 (50). Anal. Calcd. for
C11H9ClN4O (248.67): C, 53.13; H, 3.65; N, 22.53. Found: C,
53.33; H, 3.98; N, 22.33.
5-Allylsulfanyl-2-methoxy[1,2,4]triazolo[1,5-a]quinazoline
1
(9a). White solid; (yield: 70%), m.p. 123ꢁC (EtOH). H NMR
(DMSO-d6): dH 4.07 (s, 3H, CH3), 4.09 (d, J ¼ 10.12 Hz, 2H,
ACH2¼¼CHCH2), 5.22–5.50 (m, 2H, ACH2¼¼CHCH2) 5.99–
6.09 (m, 1H, ACH2¼¼CHCH2), 7.63–8.22 (m, 4H, ArH); 13C
NMR (DMSO-d6): dC 32.03 (ACH2¼¼CHCH2), 56.67 (CH3),
114.81, 116.99 (CArom), 118.94 (ACH2¼¼CHCH2), 125.54
(CArom), 132.59 (ACH2¼¼CHCH2), 133.54 (CArom), 135.57 (C-
guanidine), 165.88 (C-thioether), 169.24 (C-isourea). ms: m/z
(%): 272 (Mþ, 31), 258 (5), 200 (11), 145 (20), 104 (34).
Anal. Calcd. for C13H12N4OS (272.33): C, 57.34; H, 4.44; N,
20.57; S, 11.77. Found: C, 57.70; H, 4.32; N, 20.53; S, 11.48.
2-Benzyloxy-5-methylsulfanyl[1,2,4]triazolo[1,5-a]quinazo-
1
line (9b). Yellow solid; (yield: 73%), m.p. 185ꢁC (EtOH). H
5-Chloro-2-pentyloxy[1,2,4]triazolo[1,5-a]quinazoline (10c).
1
NMR (DMSO-d6): dH 2.45 (s, 3H, CH3), 5.34 (s, 2H, CH2),
7.20–8.86 (m, 9H, ArH); 13C NMR (DMSO-d6): dC 12.69
(CH3), 69.78 (CH2), 113.19, 114.79, 123.25, 125.45, 125.78,
127.78, 128.26, 131.87, 132.14, 135.45 (CArom), 136.69 (C-
guanidine), 152.67 (C-thioether), 168.11 (C-isourea). ms: m/z
(%): 322 (Mþ, 24), 232 (13), 201 (22), 104 (43), 91 (25).
Anal. Calcd. for C17H14N4OS (322.39): C, 63.34; H, 4.38; N,
17.38; S, 9.95. Found: C, 63.02; H, 4.32; N, 17.24; S, 10.01.
2-Methoxy-5-prop-2-ynylsulfanyl[1,2,4]triazolo[1,5-a]quin-
azoline (9c). Pale brown solid; (yield: 61%), m.p. 190ꢁC
(EtOH). 1H NMR (DMSO-d6): dH 3.23 (s, 1H, HCBCCH2-),
4.20 (s, 3H, CH3), 4.45 (s, 2H, HCBCCH2-), 7.60–8.34 (m, 4H,
ArH); 13C NMR (DMSO-d6): dC 18.45 (HCBCCH2-),
57.11(CH3), 79.57 (HCBCCH2), 80.74 (HCBCCH2-), 115.23,
117.04, 125.64, 125.79, 126.28, 133.91, 136.16 (CArom), 151.02
(C-guanidine), 165.08 (C-thioether), 169.60 (C-isourea). ms: m/z
(%): 270 (Mþ, 100), 201 (8), 187 (13), 104 (4), 91 (21). Anal.
Calcd. for C13H10N4OS (270.31): C, 57.76; H, 3.73; N, 20.73; S,
11.86. Found: C, 57.61; H, 3.90; N, 21.08; S, 11.55.
2-Methoxy-5-methylsulfanyl[1,2,4]triazolo[1,5-a]quinazoline
(9d). Yellow solid; (yield: 60%), m.p. 146ꢁC (EtOH). 1H
NMR (DMSO-d6): dH 2.73 (s, 3H, SCH3), 4.07 (s, 3H, OCH3),
7.66–8.22 (m, 4H, ArH); 13C NMR (DMSO-d6): dC 31.45
(SCH3), 56.64 (OCH3), 114.21, 122.27, 125.32, 131.81,
132.52, 135.88 (CArom), 140.47 (C-guanidine), 159.22 (C-thio-
ether), 166.20 (C-isourea). ms: m/z (%): 246 (Mþ, 37), 232
(54), 145 (6), 120 (8), 102 (31). Anal. Calcd. for C11H10N4OS
(246.29): C, 53.64; H, 4.09; N, 22.75; S, 13.02. Found: C,
53.91; H, 3.86; N, 22.45; S, 12.81.
Pale brown solid; (yield: 81%), m.p. 110ꢁC (THF-hexane). H
NMR (DMSO-d6): dH 0.96 (t, J ¼ 7.45 Hz, 3H, ACH2CH2
CH2CH2CH3), 1.37–1.47 (m, 4H, ACH2CH2CH2CH2CH3),
1.83–1.89 (m, 2H, ACH2CH2CH2CH2CH3), 4.43 (t, J ¼ 7.60
Hz, 2H, ACH2CH2CH2CH2CH3), 7.45–8.16 (m, 4H, ArH);
13C NMR (DMSO-d6): dC 13.75 (ACH2CH2CH2CH2CH3),
21.70 (CH2CH2CH2CH2CH3), 27.35 (ACH2CH2CH2CH2CH3),
28.16 (ACH2CH2CH2CH2CH3), 69.52 (ACH2CH2CH2CH2
CH3), 114.70, 116.81, 126.54, 127.95, 135.57 (CArom), 146.63
(C-guanidine), 155.33 (CACl), 166.57 (C-isourea). ms: m/z
(%): 290 (Mþ, 66), 220 (90), 160 (5), 134 (18), 104 (31), 43
(27). Anal. Calcd. for C14H15ClN4O (290.75): C, 57.83; H,
5.20; N, 19.27. Found: C, 57.93; H, 5.29; N, 18.98.
2-Benzyloxy-5-chloro[1,2,4]triazolo[1,5-a]quinazoline (10d).
1
White solid; (yield: 90%), m.p. 130ꢁC (THF-hexane). H NMR
(DMSO-d6): dH 5.79 (s, 2H, CH2), 7.37–8.45 (m, 9H, ArH),
13C NMR (DMSO-d6): dC 71.34 (CH2), 115.20, 117.42,
125.50, 126.71, 127.14, 128.07, 128.70, 132.41, 135.90, 136.11
(CArom), 136.77 (C-guanidine), 155.93 (CACl), 165.25 (C-iso-
urea). ms: m/z (%): 310 (Mþ, 89), 220 (32), 189 (4), 104 (21),
91 (100). Anal. Calcd. for C16H11ClN4O (310.75): C, 61.84; H,
3.57; N, 18.03. Found: C, 61.80; H, 3.82; N, 17.88.
5-Chloro-2-phenethyloxy[1,2,4]triazolo[1,5-a]quinazoline (10e).
1
White solid; (yield: 91%), m.p. 140ꢁC (THF-hexane). H NMR
(DMSO-d6): dH 3.15 (t, J ¼ 7.50 Hz, 2H, CH2CH2Ph), 4.65 (t,
J ¼ 7.51 Hz, 2H, CH2CH2Ph), 7.22–8.37 (m, 9H, ArH); 13C
NMR (DMSO-d6): dC 35.09 (CH2CH2Ph), 69.61 (CH2CH2Ph),
114.59, 124.40, 124.83, 126.72, 128.74, 129.30, 134.29, 134.94,
138.49 (CArom), 153.37 (C-guanidine), 156.84 (CACl), 168.61
(C-isourea). ms: m/z (%): 324 (Mþ, 100), 220 (3), 145 (32),
104 (11), 90 (34). Anal. Calcd. for C17H13ClN4O (324.77): C,
62.87; H, 4.03; N, 17.25. Found: C, 62.57; H, 4.22; N, 17.15.
2-Alkoxy(aralkoxy)-5-chloro[1,2,4]triazolo[1,5-a]quinazo-
lines (10a–e). General procedure. Method-A: Compound 5
(2 mmol) was refluxed with oxalyl chloride (6 mmol) in 1,1,2-
trichloroethane (12 mL) for 19 h at 105ꢁC. The solution was
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

662
R. Al-Salahi and D. Geffken
Vol 48
[5] Alagarsamy, V.; Solomon, V. R.; Murugan, M. Bioorg Med
Chem 2007, 15, 4009.
1,2,4,5-Tetrahydro[1,2,4]triazolo[1,5-a]quinazolin-2,5-
dione (11). A mixture of 5f (1 mmol) and Pd-C 10% (120
mg) as a catalyst was hydrogenated in THF (75 mL) for 2 h.
The suspension was filtered off and the solvent evaporated.
The resulting solid was suspended in EtOAc (2 mL) and fil-
tered again to afford analytically pure 11 as white solid; ꢀ(y1ield:
.
1H
[6] Alagarsamy, V.; Giridhar, R.; Yadav, M. R. Bioorg Med
Chem Lett 2005, 15, 1877.
[7] Michael, A. O.; Ward, H. O. EP 519868; Chem Abstr 1992,
118, 168717.
[8] Selby, T. P.; Lepone, G. E. J Heterocycl Chem 1984, 21, 61.
[9] Webb, L. R.; Labaw, C. S. J Heterocycl Chem 1982, 19,
1205.
95%), m.p. 177ꢁC (EtOAc). IR (KBr) 1707, 1686 cm
NMR (DMSO-d6): dH 7.45–8.15 (m, 4H, ArH), 11.84 (s, 1H,
NH), 12.98 (s, 1H, NH); 13C NMR (DMSO-d6): dC 114.18,
116.64, 125.11, 128.58, 135.71, 136.24 (CArom), 147.43 (C-
guanidine), 160.04 (C¼¼O), 167.01 (C¼¼O). ms: m/z (%) 202
(Mþ, 100), 106 (3), 134 (70), 105 (25), 76 (15). Anal. Calcd.
for C9H6N4O2 (202.17): C, 53.47; H, 2.99; N, 27.71. Found:
C, 53.67; H, 3.02; N, 27.52.
[10] Somorai, T.; Jerkovich, G.; Dvortsak, P. J Heterocycl Chem
1982, 19, 1157.
[11] Heckendorn, R.; Winkler, T. Helv Chim Acta 1980, 63, 1.
[12] Sheehan, J. C.; Nafissi-V, M. M. J Org Chem 1970, 12,
4246.
[13] Takahata, H.; Hashizume, T.; Yamazaki, T. Heterocycles
1979, 12, 1449.
[14] Muin, D. Z.; Misic-V, M. M.; Petrovic, S. D. J Serb Chem
Soc 2004, 69, 711.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet