8
70
Chem. Pharm. Bull.
Vol. 63, No. 11 (2015)
7
-(Benzo[d][1,3]dioxol-5-yl)-5-thioxo-5,6-dihydrotetrazolo-
1,5-f]pyrimidine-8-carbonitrile (7)
To a solution of thioxodihydropyrimidine derivative 5
4-(Benzo[d][1,3]dioxol-5-yl)-2-(ethylthio)-6-thioxo-1,6-
dihydropyrimidine-5-carbonitrile (11)
A mixture of chloropyrimidine derivative 10 (3.19g,
[
(2.92g, 0.01mol) in glacial acetic acid (30mL), sodium 0.01mol), thiourea (0.76g, 0.01mol), in ethanol (20mL) was
azide (0.65g, 0.01mol), was added. The reaction mixture refluxed for 6h, cooled. The precipitated solid was filtered,
was refluxed for 5h and allowed to cool. The solid formed dried and recrystallized from ethanol to afford compound 11
was collected, dried and recrystallized from ethanol to give as orange crystals, mp 212–214°C, yield 88%. FT-IR (KBr,
−
1
1
compound 7 as brown crystals, mp >300°C, yield 63%. cm ): 3194 νNH, 2218 νC≡N, 1667 νC=N, 1240 νC=S. H-NMR
−1
1
FT-IR (KBr, cm ): 3217 νNH, 2216 νC≡N, 1612 νC=N. H-NMR (300MHz, DMSO-d ): 13.02 (brs, 1H, –NH, D O-exchange-
6
2
(
300MHz, DMSO-d ): 7.77–7.07 (m, 3H, Ar-H), 6.13 (s, 2H, able), 7.16–6.95 (m, 3H, Ar-H), 6.16 (s, 2H, O–CH –O), 3.50
6
2
O–CH –O) and 3.40 (brs, 1H, –NH, D O-exchangeable). (q, 2H, –CH CH , J=6.9Hz) and 1.06 (t, 3H, –CH CH ,
2
2
2
3
2
3
+
·
+·
MS m/z: 298 (M ). Anal. Calcd for C H N O S (298.28): C, J=6.9Hz). MS m/z: 317 (M ). Anal. Calcd for C H N O S
8.32; H, 2.03; N, 28.17; S, 10.75. Found: C, 48.23; H, 1.98; N, (317.39): C, 52.98; H, 3.49; N, 13.24; S, 20.21. Found: C, 52.89;
8.23; S, 10.89.
-(Benzo[d][1,3]dioxol-5-yl)-10-oxo-1-thioxo-2,10-
dihydro-1H-pyrimido[6,1-b]quinazoline-4-carbonitrile (8)
A mixture of thioxodihydropyrimidine derivative 5 (2.92g,
12
6
6
2
14 11
3
2 2
4
2
H, 3.36; N, 13.11; S, 20.03.
6 -(Ben zo[d ][1,3]dioxol-5-yl)-2,4 -dioxo-1, 2,3,4 -
tetrahydropyrimidine-5-carbonitrile (12)
3
A solution of tetrahydropyrimidine 1 (2.73g, 0.01mol)
0
(
.01mol), and anthranilic acid (1.37g, 0.01mol) in ethanol in sodium hydroxide (20mL, 10%), was refluxed for 8h,
50mL) was refluxed for 6h, cooled, filtered, dried and re- cooled, acidified with dil. HCl to give precipitates, which
crystallized from ethanol to afford compound 8 as pale brown were filtered, dried and recrystallized from ethanol to give
−1
crystals, mp 270–272°C, yield 68%. FT-IR (KBr, cm ): compound 12 as yellow crystals, mp 268–270°C, yield 70%.
−1
3346, 3209 νNH, 2216 νC≡N, 1645 νC=O pyrimidinone, 1605 FT-IR (KBr, cm ): 3440 νNH, 2232 νC≡N, 1702 νC=O, 1660
1
1
νC=N, 1247 νC=S. H-NMR (300MHz, DMSO-d ): 8.10 (brs,
ν
, H-NMR (300MHz, DMSO-d ): 13.09 (s, 2H, –2NH,
6
C=N . 6
1
H, –NH, D O-exchangeable), 7.50–7.13 (m, 7H, Ar-H), D O-exchangeable), 7.25–7.09 (m, 3H, Ar-H), 6.17 (s, 2H, O–
2
2
+
·
13
6.17 (s, 2H, O–CH –O). MS m/z: 374 (M ). Anal. Calcd for CH –O). C-NMR (75MHz, DMSO-d ): 90.17, 102.10, 108.39,
2
2
6
C H N O S (374.37): C, 60.96; H, 2.69; N, 14.97; S, 8.56. 109.02, 114.81, 122.51, 123.70, 147.08, 150.47, 158.50, 160.21,
1
9
10
4
3
+
·
Found: C, 60.82; H, 2.58; N, 14.89; S, 8.47.
176.04. MS m/z: 257 (M ). Anal. Calcd for C H N O (257.2):
12 7 3 4
4
-(Benzo[d][1,3]dioxol-5-yl)-2-(ethylthio)-6-oxo-1,6- C, 56.04; H, 2.74; N, 16.34. Found: C, 55.98; H, 2.63; N, 16.22.
dihydropyrimidine-5-carbonitrile (9)
4 -A m i n o -7- (1, 3 - b e n z o d ioxol -5 -yl) -9 - oxo -9H -
A solution of tetrahydropyrimidine 1 (2.73g, 0.01mol) in pyrimido[4′,5′:4,5][1,3]thiazolo[3,2-a]pyrimidine-8-carbonitrile
ethanolic solution of sodium ethoxide (20mL), ethyl iodide (13)
(1.82g, 0.01mol), was added then refluxed for 6h. Left to cool,
A solution of enaminonitrile 2 (1.69g, 0.005mol) in for-
the solid was filtered, dried and recrystallized from ethanol mamide (10mL) was heated under reflux for 4h, cooled and
to give compound 9 as yellow crystals, mp 274–275°C, yield poured onto ice. The product was collected by filtration, dried
−1
5
5%. FT-IR (KBr, cm ): 3167 νNH, 3082 νCH aromatic, 2969 and recrystallized from ethanol to give pyrimidothiazolopy-
ν
aliphatic, 2234 νC≡N, 1705 νC=O pyrimidinone, 1672 νC=N
.
rimidine 13 as brown crystals, mp 154–156°C, yield 42%.
CH
1
−1
H-NMR (300MHz, DMSO-d ): 13.10 (s, 1H, –NH, D O-ex- FT-IR (KBr, cm ): 3313, 3190 νNH2, 2207 νC≡N, 1668 νC=O.
changeable), 7.24–7.10 (m, 3H, Ar-H), 6.17 (s, 2H, O–CH –O),
6
2
1
H-NMR (300MHz, DMSO-d ): 9.44 (brs, 2H, –NH , D O-
2
6 2 2
3
.45 (q, 2H, –CH CH , J=6.0Hz) and 1.55 (t, 3H, –CH CH , exchangeable), 8.40 (s, 1H, pyrimidine-H ), 7.42–6.84 (m,
2 3 2 3 2
13
+·
J=6.0Hz). C-NMR (75MHz, DMSO-d ): 14.30, 14.57, 62.78, 3H, Ar-H), 6.13 (s, 2H, O–CH –O). MS m/z: 364 (M ). Anal.
6
2
100.08, 102.54, 108.99, 109.34, 126.21, 129.97, 154.42, 154.80, Calcd for C H N O S (364.34): C, 52.75; H, 2.21; N, 23.07; S,
16 8 6 3
+
·
178.65. MS m/z: 301 (M ). Anal. Calcd for C H N O S 8.80. Found: C, 52.61; H, 2.12; N, 23.18; S, 8.74.
14 11 3 3
(
301.32): C, 55.80; H, 3.68; N, 13.95; S, 10.64. Found: C, 55.68;
7-(1,3-Benzodioxol-5-yl)-4,9-dioxo-1,4-dihydro-9H-
pyrimido[4′,5′:4,5][1,3]thiazolo[3,2-a]pyrimidine-8-carbonitrile
H, 3.75; N, 13.78; S, 10.60.
4
-(Benzo[d][1,3]dioxol-5-yl)-6-chloro-2-(ethylthio)- (14)
pyrimidine-5-carbonitrile (10)
A solution of enaminonitrile 2 (1.69g, 0.005mol) in formic
A mixture of S-alkylated pyrimidine 9 (3.01g, 0.01mol), acid (10mL) was heated under reflux for 10h, cooled and then
was heated under reflux in phosphorus oxychloride (7mL, poured onto ice. The precipitate solid was collected by filtra-
0.01mol) and phosphorus pentchloride (2.5g, 0.01mol) for 8h, tion, dried and recrystallized from ethanol to give compound
cooled and poured onto ice. The precipitated solid was filtered 14 as brown crystals, mp 234–236°C, yield 45%. FT-IR (KBr,
−
1
1
off, dried and recrystallized from ethanol to give compound cm ): 3392 νNH, 2219 νC≡N, 1683 νC=O. H-NMR (300MHz,
0 as brown crystals, mp 220–222°C, yield 73%. FT-IR (KBr, DMSO-d ): 12.67 (s, 1H, –NH, D O-exchangeable), 8.44 (s,
1
6
2
−1
cm ): 3205 ν
aromatic, 2914 νCH aliphatic, 2222 νC≡N
,
1H, pyrimidine-H ), 8.23–7.14 (m, 3H, Ar-H) and 6.19 (s, 2H,
H-NMR (300MHz, DMSO-d ): 7.30–6.95 (m, O–CH –O). MS m/z: 365 (M ). Anal. Calcd for C H N O S
CH
2
1
+·
1655 νC=N
.
6
2
16
7
5
4
3
H, Ar-H), 6.17 (s, 2H, O–CH –O), 3.43 (q, 2H, –CH CH , (365.32): C, 52.60; H, 1.93; N, 19.17; S, 8.78. Found: C, 52.54;
2
2
3
J=7.5Hz), 1.06 (t, 3H, –CH CH , J=7.5Hz). MS m/z: 319 H, 1.79; N, 19.02; S, 8.78.
2
3
+
·
(
M ). Anal. Calcd for C H ClN O S (319.77): C, 52.59; H,
7- (1, 3 - B e n z o d ioxol -5 -yl) - 4 - c h lo r o -9 - oxo -9H -
14
10
3
2
3
.15; Cl, 11.09; N, 13.14; S, 10.03. Found: C, 52.45; H, 3.03; Cl, pyrimido[2′,1′:2,3][1,3]thiazolo[4,5-d][1,2,3]triazine-8-
11.00; N, 13.02; S, 10.14.
carbonitrile (15)
A solution of sodium nitrite in 10mL H O was added to a
2
cold solution of enaminonitrile 2 (1.69g, 0.005mol), in acetic