A. El-Shafei et al. / Bioorg. Med. Chem. 17 (2009) 5096–5105
5103
5
3
.2.3. Reaction of (2) with benzoyl isothiocyanate: formation of
,5-diamino-4-(4-phenylazo-phenylazo)-pyrazol-3-yl-
20 18 8
C H N (370.4): C, 64.8; H, 4.90; N, 30.3. Found: C, 65.0; H, 4.6;
N, 30.6.
benzoylthiourea (3)
To a solution of benzoyl isothiocyanate, 2 (30.63 g, 0.1 mol) in
acetone (50 ml) was added. The reaction mixture was refluxed
for 2 h and then poured in to water; the resulting solid product
was filtered off and recrystallized from ethanol. Yield: 70%. Mp:
5
.2.8. Synthesis of 3,6-bis-(4-phenylazo-phenylazo)-2,5,7-
triaminopyrazolo[1,5-a]pyrimidine (9)
A mixture of 2 (30.63 g, 0.1 mol) and 1 (27.43 g, 0.1 mol) was
refluxed in DMF for 1 h. The reaction mixture was then poured
into water; the solid product was collected by filtration and
ꢀ1
1
1
2
90 °C. IR (KBr/
680 (CO) and 1300 (C@S). H NMR (DMSO, 200 MHz): d 5.1 (s,
H, NH ), 7.3–8.0 (m, 14H, Ar-H), 8.4 (s, 1H, NH), 9.0 (s, 1H, NH)
(420.4): C, 65.7; H,
2
m, cm ): 3350–3380 (NH ), 3280, 3330 (NH),
1
recrystallized from DMF/H
2
O mixture. Yield: 60%. Mp: >300 °C.
, NH), and 1600–1550
), 2.85 (s,
), 7.4–8.1 (m, 18H, Ar-H). MS: 581
M ), 522, 391, 337, 256, 201, 128 and 77. Anal. Calcd for
ꢀ1
2
IR (KBr/
m
, cm ): 3411, 3275, 3150 (NH
2
and 9.3 (s, 1H, NH). Anal. Calcd for C23
H
8
N
9
1
(
N@N). H NMR (DMSO, 200 MHz): d 2.75 (s, 2H, NH
2
4
.30; N, 30.0. Found: C, 65.4; H, 4.0; N, 29.8.
2
(
H, NH ), 6.92 (s, 2H, NH
2
2
+
5
.2.4. Synthesis of 7-amino-2-(4-phenylazophenylazo)-2,3-
C
4
30 24
H N14 (580.6): C, 62.1; H, 4.20; N, 33.8. Found: C, 62.4; H,
.0; N, 33.5.
dihydro-3-oxo-4H-pyrazolo[3,4-e]-as-triazine (4)
To a suspension of 3 (4.695 g, 0.01 mol) in acetic acid (20 ml),
concentrated HCl (2 ml) was added. The reaction mixture was re-
fluxed for 30 min., and then poured into water. The solid product
was collected by filtration and crystallization from acetic acid.
5
.2.9. Synthesis of 3-amino-4-(4-phenylazo-
phenylazo)pyrazole-5-diazonium salt from compound 2
A suspension of 2 (30.63 g, 0.1 mol) in acetic acid was heated to
produce a clear solution then cooled to 5 °C. A solution of sodium
nitrite (6.9 g, 0.1 mol) in water (30 ml) gradually added with stir-
ring. The reaction mixture was left in refrigerator for 2 h, and then
poured into cold water; the separated solid product was collected
by filtration and washed several times with water.
ꢀ
1
Yield: 60%. Mp: 175 °C. IR (KBr/
1
m
, cm ): 3450 (NH
700 (CO) and 1600 (N@N). H NMR (DMSO, 200 MHz): d 5.2 (s,
H, NH ), 7.3–8.0 (m, 9H, Ar-H) and 9.0 (s, 1H, NH). MS: 335
2
), 3320 (NH),
1
2
(
2
+
M ), 329, 323, 271, 237, 208, 167 and 57. Anal. Calcd for
16 12 8
C H N O (332.33): C, 57.8; H, 3.60; N, 33.7. Found: C, 58.0; H,
3
.4; N, 33.8.
5
.2.5. Synthesis of 2-amino-5-imino-4,5,6,7-tetrahydro-3-(4-
5.2.10. Coupling of diazonium salt of compound (2) with b-
naphthol, ethyl acetoacetate, malononitrile, ethyl cyanoacetate
1-phenylpyrazolin-5-one and acetylacetone
phenylazophenylazo)-pyrazolo[1,5-a]pyrimidine (5)
A solution of 2 (30.63 g, 0.1 mol), in pyridine (40 ml) and water
(
10 ml) was treated with ethyl acrylate (10.01 g, 0.1 mol); the mix-
General procedure for preparation of 10, 12, 13, 14, 17 and 18: A
solution of active hydrogen compounds (0.1 mol) in ethanol
(100 ml) was treated with a suspension of sodium acetate
(0.1 mol) in (50 ml) of water. A solution of diazonium salt of 2
(30.63 g, 0.1 mol) in acetic acid (50 ml) was then added with stir-
ring. The solid product, obtained on standing was collected by fil-
tration and washed several times with hot water. 10; Yield: 70%.
ture was refluxed for 4 h. The reaction mixture was then poured into
water and the solid product was collected by filtration and recrystal-
lized from ethanol. Yield: 90%. Mp: 240 °C. IR (KBr/
3
2
8
ꢀ1
m
, cm ): 3390–
), 3120 (NH) and 1600 (N@N). H NMR (DMSO,
00 MHz): d 2.1 (t, 2H, CH ), 2.7 (t, 2H, CH ), 5.1 (s, 2H, NH ), 7.1–
.0 (m, 9H, Ar-H) and 8.8 (s, 1H, NH). Anal. Calcd for C18
1
330 (NH
2
2
2
2
17 9
H N
ꢀ1
(
359.4): C, 60.2; H, 4.80; N, 35.1. Found: C, 60.3; H, 5.0; N, 35.4.
Mp: 105 °C. IR (KBr/
m
, cm ): 3450, 3400 (NH
2
), 3300 (OH), and
1
1
600–1580 (N@N). H NMR (DMSO, 200 MHz): d 2.3 (s, 1H,
5
.2.6. Synthesis of 2-amino-4,5,6,7-tetrahydro-3-(4-phenylazo-
2
OH), 5.1 (s, 2H, NH ), 7.1–7.8 (m, 15H, Ar-H) and 8.1 (s, 1H,
+
phenylazo)-pyrazolo[1,5-a]pyrimidin-5-one (6)
NH). MS: 461 (M ), 445, 318 and 290. Anal. Calcd for
O (461.5): C, 65.1; H, 4.10; N, 27.3. Found: C, 65.0; H,
To a suspension of 5 (35.94 g, 0.1 mol) in acetic acid (30 ml) was
treated with concentrated HCl (5 ml, 37.5%). The reaction mixture
was refluxed for 2 h, and then poured into water; the product was
filtered off and recrystallized from ethanol. Yield: 80%. Mp: 210 °C.
25 19 9
C H N
4.0; N, 27.4.
ꢀ
1
Compound 12; Yield: 70%. Mp: 110 °C. IR (KBr/
m
, cm 1):
3500–3300 (NH
NMR (DMSO, 200 MHz): d 1.0 (t, 3H, CH
CH ), 4.1 (q, 2H, CH –CH ), and 5.0 (s, 2H, NH
for C21 (397.4): C, 63.5; H, 4.80; N, 31.7. Found: C, 63.2;
2
, NH), 1715 (CO), 1610 and 1550 (2N@N).
H
ꢀ
1
1
IR (KBr/
m
, cm ): 3390, 3330 (NH
2
), 3120 (NH), 1670 (ring CO) and
600 (N@N). H NMR (DMSO, 200 MHz): d 2.5 (t, 2H, CH ), 2.9 (t,
H, CH ), 4.9 (s, 2H, NH ), 7.1–8.0 (m, 9H, Ar-H) and 8.4 (s, 1H,
3
–CH
2
), 2.2 (s, 3H,
2
). Anal. Calcd
1
2
2
3
3
2
19 9
H N
2
2
+
NH). MS: 360 (M ), 306, 255, 217, 197, 167, 92 and 77. Anal. Calcd
for C18 O (360.4): C, 60.0; H, 4.50; N, 31.1. Found: C, 59.9; H,
H, 5.0; N, 31.4.
ꢀ
H
16
N
8
Compound 13; Yield: 80%. Mp: 275 °C. IR (KBr/
m
, cm 1): 3500–
+
4
.2; N, 31.0.
3300 (NH
78, 257, 201, 140, 91 and 77. Anal. Calcd for C18
C, 56.4; H, 3.40; N, 40.2. Found: C, 56.2; H, 3.2; N, 40.1.
Compound 14; Yield: 75%. Mp: 165 °C. IR (KBr/
, cmꢀ1): 3500–
3300 (NH , NH), 2220 (conjugated CN), 1715 (ester CO), 1600 and
1590 (N@N). H NMR (DMSO, 200 MHz): d 1.2 (t, 3H, CH
(q, 2H, CH –CH ), 4.9 (s, 2H, NH ), 7.0–7.7 (m, 9H, Ar-H) and 8.1 (s,
1H, NH). Anal. Calcd for C20
32.5. Found: C, 55.5; H, 4.1; N, 32.8.
Compound 17; Yield: 75%. Mp: 240 °C. IR (KBr/
2
, NH), 2220 (CN), 1600 and 1610 (N@N). MS: 383 (M ),
2
13
H N11 (383.4):
5
.2.7. Reaction of (2) with ethyl acetoacetate and acetylacetone:
(
general procedure for the synthesis of 7 and 8)
m
Equimolar amounts of 2 (3.063 g, 0.01 mol) and ethyl acetoace-
2
1
tate (1.301 g, 0.01 mol) or acetylacetone (1.001 g, 0.01 mol) were
heated at 160 °C (bath temp.) for 8 h. The solid product was filtered
and crystallized from the proper solvent. Compound 7; Yield: 80%.
3 2
–CH ), 4.1
3
2
2
H
18
N
10
O
2
(430.4): C, 55.8; H, 4.20; N,
ꢀ1
Mp: >300 °C. IR (KBr/
m
, cm ): 3400 (NH
CO). H NMR (DMSO, 200 MHz): d 2.5 (s, 3H, CH
ring), 7.0–8.0 (m, 9H, Ar-H) and 11.1 (s, 1H, NH). Anal. Calcd for
O (372.4): C, 61.3; H, 4.30; N, 30.1. Found: C, 61.1; H, 4.2;
2
), 3330 (NH) and 1700
1
ꢀ1
(
3
), 5.6 (s, 1H, CH
m
, cm ): 3500–
3350 (chelated NH), 1670 (pyrazolone CO) and 1600, 1580 (N@N).
1
C
19
H
16
N
8
H NMR (DMSO, 200 MHz): d 5.1 (s, 2H, NH
lone CH), 7.2–7.8 (m, 15H, Ar-H), 8.0 (s, 1H, NH) and 9.1 (s, 1H,
NH). Anal. Calcd for C24 11 (477.48): C, 60.37; H, 4.01; N,
2
), 7.0 (s, 1H, pyrazo-
N, 30.0.
Compound 8; Yield: 70%. Mp: 220 °C. IR (KBr/
380 (NH ), 3310 d (NH), 1600 (N@N) and 1580 (C@C). H NMR
DMSO, 200 MHz): d 2.2 (s, 3H, CH ), 2.3 (s, 3H, CH ), 5.5 (s, 1H,
-ring), 5.7 (s, 2H, NH ), 7.1–8.0 (m, 9H, Ar-H). Anal. Calcd for
ꢀ
1
m
, cm ): 3420,
19
H N
1
3
(
H
2
32.27. Found: C, 60.33; H, 4.21; N, 32.29.
Compound 18; Yield: 75%. Mp: 240 °C. IR (KBr/m
, cm 1): 3400–
ꢀ
3
3
1
2
3300 (NH , NH), 1730 (CO), 1600 and 1580 (N@N). H NMR (DMSO,
6
2