Arch. Pharm. Chem. Life Sci. 2005, 338, 433−440
Substituted Pyridine and Pyrimidine Derivatives
439
2,6-Bis-[3Ј-ethyl-5Ј,6Ј,7Ј,8Ј-tetrahydro-4ЈH-cyclohepta[b]thien-car-
boxylate-2Ј-yl]pyrrolo[3,4-f]isoindole-1,3,5,7-tetraone (7)
refluxed for 3 h. The solvent was evaporated under reduced pres-
sure, the residue was dissolved in water and neutralized with 1N
hydrochloric acid. The solid formed was collected by filtration and
crystallized from the proper solvent to give the corresponding thiox-
opyrimidines 11aϪf, respectively (Table 4).
IR (KBr, cmϪ1): 1723 (CϭO, ester), 1677 (CϭO, imide). 1H-NMR
(DMSO-d6) δ: 1.30-1.95 (m, 20H, 10 ϫ CH2, cycloheptyl ring), 2.05
(t, 6H, 2 ϫ CH3), 4.25 (q, 4H, 2 ϫ CH2), 7.90 (s, 2H, Ar-H). MS
m/z (%): 660 (Mϩ, 35) corresponding to the molecular formula
C34H32N2O8S2 and at 514 (100, base peak).
4a-Hydroxy-8-[hydroxyl-(4-methoxyphenyl)methyl]-4-(4-methoxy-
phenyl)-3,4,4a,5,6,7-hexahydro-1H-quinazolin-2-thione (11b)
Synthesis of 2,7-Bis-[substituted bipyridinyl or cyclohepta[b]thien]-
benzo[l,m,n][3,8]phen-anthroline Derivatives 5 and 8
IR (KBr, cmϪ1): 3400Ϫ3100 (OH, NH), 1195 (CϭS). 1H-NMR
(DMSO-d6) δ: 0.95Ϫ2.15 (m, 6H, 3 ϫ CH2), 3.70 (s, 1H, CH-Ar),
3.85 (s, 6H, 2 ϫ OCH3), 4.46 (bs, 1H, OH, which is exchangeable
with D2O), 5.40 (s, 1H, CH-pyrimidine), 7.10Ϫ7.65 (m, 8H, Ar-H),
7.85 (bs, 1H, NH which is exchangeable with D2O), 10.10 (bs, 1H,
OH, which is exchangeable with D2O), 10.20 (br, 1H, NH). MS
(m/z,%): 426 (Mϩ, 28) corresponding to the molecular formula
A mixture of compound 1 or 2 (2 mmol) and naphthalene tetracar-
boxylic dianhydride (0.268 g, 1 mmol) in glacial acetic acid (50 mL)
was heated under reflux for 6 h. The obtained solid was filtered off,
washed with acetic acid, and crystallized from DMF/H2O (2:1) and
AcOH, respectively, to afford the corresponding derivatives 5 and 8
(Table 4).
C
23H26N2O4S and at 319 (100, base peak).
2,7-Bis-[2ЈЈ-chloro-6ЈЈ-ethoxy-4Ј-thien-2Ј-yl-[2Ј,4ЈЈ]bipyridinyl-5Ј-
carbonitril-6Ј-yl]benzo[l,m,n]phenanthroline-1,3,6,8-tetraone (5)
4a-Hydroxy-9-[hydroxyl-(4-methoxyphenyl)methyl]-4-(4-methoxy-
phenyl)-1,3,4,4a,5,6,7,8-octa-hydrocycloheptapyrimidine-2-thione
(11e)
IR (KBr, cmϪ1): 2215 (CϵN), 1685 (two CϭO), 1636 (CϭN). MS
m/z (%): 945 (Mϩ 15) corresponding to the molecular formula
IR (KBr, cmϪ1): 3380Ϫ3200 (OH, NH), 1198 (CϭS). 1H-NMR
(CDCl3) δ: 1.20-2.10 (m, 8H, 4 ϫ CH2), 3.50 (s, 1H, CH-Ar), 3.90
(s, 6H, 2 ϫ OCH3), 4.30 (bs, 1H, OH, which is exchangeable with
D2O), 5.20 (s, 1H, CH-pyrimidine), 6.80Ϫ7.30 (m, 8H, Ar-H), 7.80
(bs, 1H, NH which is exchangeable with D2O), 9.80 (bs, 1H, OH,
which exchangeable with D2O), 10.50 (br, 1H, NH). MS m/z (%):
440 (Mϩ, 18) corresponding to the molecular formula C24H28N2O4S
and at 318 (100, base peak).
,
C48H26Cl2N8O6S2 and at 296 (100, base peak).
2,7-Bis-[3Ј-ethyl-5Ј,6Ј,7Ј,8Ј-tetrahydro-4ЈH-cyclohepta[b]thien-car-
boxylat-2Ј-yl]benzo[l,m,n][3,8]phenanthroline-1,3,6,8-tetraone (8)
IR (KBr, cmϪ1): 1715 (CϭO, ester), 1675 (CϭO, imide). 1H-NMR
(DMSO-d6) δ: 1.25Ϫ1.85 (m, 20H, 10 ϫ CH2, cycloheptyl ring),
2.15 (t, 6H, 2 ϫ CH3), 4.05 (q, 4H, 2 ϫ CH2), 7.85 (d, 4H, Ar-H).
MS m/z (%): 710 (Mϩ, 100) corresponding to the molecular formula
C38H34N2O8S2 and also as base peak.
Synthesis of Thiazolopyrimidine Derivatives 12aϪf
A mixture of compounds 11aϪf (10 mmol), chlororacetic acid
(0.95 g, 10 mmol) and anhydrous sodium acetate (1.72 g, 20 mmol)
in glacial acetic acid (30 mL) and acetic anhydride (10 mL) was
refluxed for 3 h. The reaction mixture was poured into water, the
formed solid was filtered off and crystallized from the proper sol-
vent to give the corresponding thiazolopyrimidine derivatives
12aϪf, respectively (Table 4).
Synthesis of 2,7-Bis-(aryl)-1,6-dioxa-dispirodecane-4-one Deriva-
tives 10aϪf
To a mixture of bis-arylmethylene derivatives (9aϪf) [19] (100
mmol) in acetone/dioxane (50 mL, 3:2 ratio) and sodium hydroxide
(2 g) in few drops of water, hydrogen peroxide (6 mL, 30%) was
added dropwise with stirring for 15 min. The reaction mixture was
stirred for further 8 h at room temperature, then left overnight at
Ϫ5°C. The solid formed was collected by filtration and crystallized
from proper solvent to give the corresponding bis-spiro compounds
10aϪf, respectively (Table 4).
5a-Hydroxy-9-[hydroxyl-4-(4-methoxyphenyl)methyl]-5-(4-meth-
oxyphenyl)-5a,6,7,8-tetrahydro-5H-thiazolo[2,3-b]quinazolin-3-one
(12b)
IR (KBr, cmϪ1): 3390Ϫ3310 (OH), 1683 (CϭO). MS m/z (%): 466
2,6-Bis-(4-methoxyphenyl)-1,6-dioxadispiro[2.1.2.3]decan-4-one
(10b)
(Mϩ 100, base peak) corresponding to the molecular formula
,
C25H26N2O5S.
IR (KBr, cmϪ1): 1729 (CϭO). 1H-NMR (DMSO-d6) δ: 1.15Ϫ2.10
(m, 6H, 3 ϫ CH2), 3.65 (s, 2H, 2 ϫ CH-Ar), 3.95 (s, 6H, 2 ϫ
OCH3), 7.35Ϫ7.75 (m, 8H, 2 ϫ Ar-H). MS m/z (%): 366 (Mϩ, 100),
as base peak and corresponds to the molecular formula C22H22O5.
4a-Hydroxy-9-[hydroxyl-4-(4-methoxyphenyl)methyl]-5-(4-meth-
oxyphenyl)-4,4a,5,6,7,8-hexa-hydro-1-thia-3a,10-diaza-cyclohepta-
[f]inden-3-one (12e)
IR (KBr, cmϪ1): 3375Ϫ3290 (OH), 1680 (CϭO). MS m/z (%): 480
2,7-Bis-(4-methoxyphenyl)-1,6-dioxadispiro[2.1.2.4]undecan-4-one
(10e)
(Mϩ 100, base peak) corresponding to the molecular formula
,
C
26H28N2O5S.
IR (KBr, cmϪ1): 1713 (CϭO). 1H-NMR (DMSO-d6) δ: 1.10Ϫ2.20
(m, 8H, 4 ϫ CH2), 3.60 (s, 2H, 2 ϫ CH-Ar), 3.90 (s, 6H, 2 ϫ
OCH3), 7.20Ϫ7.80 (m, 8H, 2 ϫ Ar-H). MS m/z (%): 380 (Mϩ, 16)
corresponding to the molecular formula C23H24O5 and at 348 (100,
base peak).
Synthesis of thiazoloarylarylmethylene derivatives 13aϪf
Method A: To a mixture of compounds 11a-f (10 mmol), chlo-
roacetic acid (0.95 g, 10 mmol) and anhydrous sodium acetate (1.72
g, 20 mmol) in glacial acetic acid (30 mL)/acetic anhydride (10 mL)
and p-nitrobenzaldehyde (1.51 g, 10 mmol) was added. The reaction
mixture was heated under reflux for 3 h, then cooled and poured
into water. The solid formed was collected by filtration and crys-
Synthesis of Thioxopyrimidine Derivatives 11aϪf
A mixture of compounds 10aϪf (10 mmol), thiourea (1.34 g,
20 mmol) and potassium hydroxide (1 g) in ethanol (50 mL) was
2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim