JOURNAL OF CHEMICAL RESEARCH 2007 583
was collected and recrystallised from ethanol as white crystals; yield:
2.638 g (89%); m.p. 140–142°C. IR (cm-1):1640 (C=N). 1H NMR
(CDCl3, ppm): 9.0 (s, 1H, CH-pyrimidine), 7.3 (s, 1H, CH-pyridine),
2.8 (s, 3H, CH3), 3.0 (s, 3H, CH3). MS: m/z (%): 297 (M+, 100); 299
(M+, 44). Anal: calc. for C11H8ClN3Se (296.62): C, 44.51; H, 2.69; N,
14.16. Found: C, 44.31; H, 2.63; N, 14.49.
Ethyl 7,9-dimethylpyrido[3',2':4,5]selenolo[2,3-e][1,2,4]triazolo[4,3-c]
pyrimidine-3-acetate (19)
The hydrazine 17 (2.92 g, 10 mmol) was heated under reflux with
diethyl malonate (15 ml) for 6 h. The reaction mixture was then
cooled and triturated with ethanol (15 ml). The solid that separated
was collected and recrystallised from ethanol as pale yellow crystals
(2.91 g, 75%), m.p. 224–226°C. IR: nmax 1730 cm-1 (C=O). 1H NMR
(TFA): δ 8.0 (s, 1H, CH-pyridine), 8.7 (s,1H, CH-pyrimidine), 4.6 (s,
2H, CH2), 4.2 (m, 2H, CH2-ester), 3.2 (s, 3H, CH3), 3.6 (s, 3H, CH3).
1.4 (t, 3H, CH3-ester). MS: m/z (%) 389 (M+, 41),387 (M+, 19). Anal:
calc. for C16H15N5O2Se (388.3): C, 49.48; H, 3.86; N, 18.04. Found:
C, 48.98; H, 3.55; N, 18.24%.
7,9-Dimethylpyrido[3',2':4,5]selenolo[3,2-d]pyrimidine-4(3H)-
thione (14)
Compound 13 (2.96 g, 10 mmol) and thiourea (0.76 g; 10 mmol)
were heated under reflux in ethanol (20 ml) for 3 h, and then 20
ml of 10% sodium hydroxide was added to the reaction solution
followed by further reflux for 0.5 h. The solution was then filtered
hot and the cooled filtrate was acidified with acetic acid giving a
yellow precipitate, which was collected and recrystallised from
aqueous DMF as yellow crystals (2.65 g, 90%), m.p.>300°C. IR: νmax
3,7,9-Trimethylpyrido[3',2':4,5]selenolo[2,3-e][1,2,4]triazolo[4,3-c]
pyrimidine (20)
Compound 17 (2.92 g,10 mmol) in acetic anhydride (20 ml) was
heated under reflux for 6 h. The precipitate that formed while hot
was collected and recrystallised from dioxan: white crystals (2.52 g,
80%), m.p. >300°C. IR: νmax 3050 cm-1 (CH-aromatic). 1H NMR
(TFA): δ 7.9 (s, 1H, CH-pyridine), 8.7 (s, 1H, CH-pyrimidine), 3.0
(s, 3H, CH3), 3.2 (s, 3H, CH3), 3.4 (s, 3H, CH3-triazole). Anal: calc.
for C13H11N5Se (316.2): C, 49.36; H, 3.48; N, 22.15. Found: C,
49.23; H, 3.67; N, 21.80%.
1
3400 cm-1 (NH). H NMR (DMSO-d6): 15.7 (s, 1H, SH) 8.5 (s, 1H,
CH-pyrimidine), 7.2 (s, 1H, CH-pyridine), 2.6 (s, 3H, CH3), 2.8(s,
3H, CH3). MS: m/z (%) 295 (M+, 100). Anal: calc. for C11H9N3Se
(294.24): C, 44.89; H, 3.06; N, 14.28; S, 10.88. Found: C, 45.34; H,
3.28; N, 14.76; S, 10.52%.
Ethyl [(7,9-dimethylpyrido[3',2':4,5]selenolo[3,2-d]pyrimidin-4-yl)
thio]acetate (15)
Ethyl N-(2-cyano-4,6-dimethylselenolo[2,3-b]pyridin-3-yl)methan-
imidate (21)
Ethyl chloroacetate (1.23 g, 10 mmol) was added to the thione 14
(2.94 g, 10 mmol) and anhydrous potassium carbonate in DMF
(20 ml). The mixture was heated under reflux for 2 h, and after
cooling was poured into ice-water giving a white precipitate which
was collected and recrystallised from ethanol giving white crystals
(3.15 g, 83%), m.p. 162–164°C. IR: nmax 1640 cm-1 (C=O ester). 1H
NMR (DMSO-d6): δ 8.8 (s, 1H, CH-pyrimidine), 7.2 (s, 1H, CH-
pyridine), 2.6 (s, 3H, CH3), 2.9 (s, 3H, CH3), 1.4 (t, 3H, ester CH3),
4.5 (m, 4H, OCH2, SCH2). MS: m/z (%) 307 (M+-COOEt, 100).
Anal: calc. for C15H15N3O2SSe: C, 47.36; H, 3.94; N, 11.05; S, 8.42.
Found: C, 46.98; H, 4.23; N, 10.88; S, 8.12%.
The nitrile 2b (2.5 g, 10 mmol) and triethyl orthoformate (7 ml)
were refluxed in acetic anhydride (20 ml) for 5 h. The precipitate
that formed on cooling was collected; recrystallisation from ethanol
formed white crystals (2.88 g, 94%), m.p. 132–134°C. IR: νmax
2200 cm-1 (CN). 1H NMR (DMSO-d6): 8.0 (s, 1H, N=CH), 7.0 (s, 1H,
CH-pyridine), 4.2 (m, 2H, CH2-ethoxy), 2.4 (s, 3H, CH3-pyridine).
1.8 (s, 3H, CH3-pyridine), 1.2 (t, 3H, CH3-ethoxy), MS: m/z (%): 307
(M+, 100). Anal: calc. for C13H13N3OSe (306.23): C, 50.98; H, 4.24;
N, 13.72. Found: C, 50.57; H, 3.97; N, 13.83%.
3-Amino-3,4-dihydro-4-imino-7,9-dimethylpyrido[3',2':4,5]selenolo
[3,2-d]pyrimidine (22)
Aminodechlorination reactions: preparation of 16a, b
A mixture of 13 (2.96 g, 10 mmol) in piperidine or morpholine
(4 ml) was gently heated under reflux for 2 h, the reaction mixture was
triturated with ethanol (15 ml) and than left to cool. The precipitated
solid that formed was collected and recrystallised from ethanol.
7,9-Dimethyl-4-piperidinopyrido[3',2':4,5]selenolo[3,2-d]
pyrimidine (16a): White crystals (2.93 g, 85%), m.p. 132–134°C.
1H NMR (DMSO-d6): δ 8.6 (s, 1H, CH-pyrimidine), 7.3 (s, 1H,
CH-pyridine), 1.5 (m, 6H, 3CH2-piperidine), 2.8 (m, 4H, 2CH2-
piperidine), 2.7 (s, 3H, CH3), 3.0 (s, 3H, CH3), MS: m/z (%) 346 (M+,
100). The Anal: calc. for C16H18N4Se (345.3): C, 55.65; H, 5.21; N,
16.23. Found: C, 55.84; H, 5.34; N, 15.96%.
7,9-Dimethyl-4-morpholinopyrido[3',2':4,5]selenolo[3,2-d]
pyrimidine (16b): White crystals (3.15 g, 91%), m.p. 166–168°C.
1H NMR (DMSO-d6): 9.8 (s, 1H, CH-pyrimidine), 7.8 (s, 1H,
CH-pyridine), 4.3 (m, 4H, 2CH2-morpholine), 4.5 (m, 4H, 2CH2-
morpholine), 3.1 (s, 3H, CH3), 3.3 (s, 3H, CH3). MS: m/z (%) 348
(M+, 100%). Anal: calc. for C15H16N4OSe (347.3): C, 51.87; H, 4.61;
N, 16.13. Found: C, 51.57; H, 4.68; N, 15.88%.
The iminoether 21 (3.06 g, 10 mmol) was suspended in dioxan
(10 ml), hydrazine hydrate (99%, 2 ml) was added, the reaction
mixture was stirred at room temperature for 3 h. The solid product
that formed was collected and recrystallised from dioxan as white
crystals (2.54 g, 87%), m.p. >300°C. IR: νmax 3100 (NH), 3300,
3400 cm-1 (NH2). 1H NMR (DMSO-d6): δ 8.0 (s, 1H, CH-pyrimidine),
7.0 (s, 1H, CH-pyridine), 5.8 (s, 2H, NH2), 2.7 (s, 3H, CH3), 2.4 (s,
3H, CH3), MS: m/z (%) 292 (M+-1, 93). Anal: calc. for C11H11N5Se
(292.2): C, 45.20; H, 3.76; N, 23.97. Found: C, 45.31; H, 3.31; N,
24.28%.
7,9-Dimethylpyrido[3',2':4,5]selenolo[2,3-e][1,2,4]triazolo[1,5-c]
pyrimidine (23)
The amino-imine 22 (2.92 g, 10 mmol) was heated under reflux for
4 h in triethyl orthoformate (10 ml). A solid product that separated
while hot was collected and recrystallised from dioxan as
white crystals (2.35 g, 78%), m.p. >300°C. IR: νmax 3050 cm-1
1
(CH-aromatic). H NMR (TFA): δ 8.0 (s, 1H, CH-pyridine), 8.8 (s,
1H, CH-pyrimidine), 9.0 (s, 1H, CH-triazole), 3.4 (s, 3H, CH3), 3.0
(s, 3H, CH3). MS: m/z (%) 303 (M+, 100). Anal: calc. for C12H9N5Se
(302.2): C, 47.68; H, 2.98; N, 23.17. Found: C, 47.53; H, 3.06; N,
23.42%.
4-Hydrazino-7,9-dimethylpyrido[3',2':4,5]selenolo[3,2-d]pyrimidine (17)
The chloro-compound 13 (2.96 g, 10 mmol) in ethanol (20 ml)
was heated under reflux for 2 h with hydrazine hydrate (99%,
4 ml, 40 mmol). The product that formed while hot was collected
and recrystallised from dioxan to give white crystals (2.60 g, 89%),
Ethyl 7,9-dimethylpyrido[3',2':4,5]selenolo[2,3-e][1,2,4]triazolo[1,5-c]
pyrimidine-2-acetate (24)
m.p. >300°C. IR: νmax 3100, 3300, 3400 cm-1 (NHNH2). H NMR
1
Compound 22 (2.92 g, 10 mmol) was heated under reflux with diethyl
malonate (15 ml) for 6 h. The reaction mixture was then cooled and
triturated with ethanol (15 ml). The solid that separated was collected
and recrystallised from ethanol as pale yellow crystals (2.91 g, 75%),
(DMSO-d6): δ 8.8 (s, 1H, NH), 8.3 (s, 1H, CH-pyrimidine), 7.1 (s,
1H, CH-pyridine), 4.9 (s, 2H, NH2), 2.6 (s, 3H, CH3), 2.9 (s, 3H,
CH3). MS: m/z (%) 292 (M+-1). Anal: calc. for C11H11N5Se (292.2):
C, 45.20; H, 3.76; N, 23.97. Found: C, 44.70; H, 3.50; N, 23.74%.
1
m.p. 224–226°C. IR: νmax 1730 cm-1 (C=O). H NMR (TFA): δ 8.0
(s, 1H, CH-pyridine), 8.7 (s, 1H, CH-pyrimidine), 4.6 (s, 2H, CH2),
4.2 (m, 2H, CH2-ester), 3.2 (s, 3H, CH3), 3.6 (s, 3H, CH3), 1.4 (t, 3H,
CH3-ester). MS: m/z (%) 388 (16), 389 (M+, 89), 390 (17). Anal: calc.
for C16H15N5O2Se (388.3): C, 49.48; H, 3.86; N, 18.04. Found: C,
49.39; H, 4.03; N, 17.83%.
7,9-Dimethylpyrido[3',2':4,5]selenolo[2,3-e][1,2,4]triazolo[4,3-c]
pyrimidine (18)
The hydrazine 17 (2.92 g, 10 mmol) was heated under reflux in
triethyl orthoformate (10 ml) for 4 h. A solid product that formed
while hot was collected and recrystallised from dioxan as white
1
crystals (2.35 g, 78%), m.p. >300°C. H NMR (TFA): δ 8.0 (s, 1H,
2,7,9-Trimethylpyrido[3',2':4,5]selenolo[2,3-e][1,2,4]triazolo[1,5-c]
pyrimidine (25)
Compound 22 (2.92 g,10 mmol) was heated under reflux for 6 h in
acetic anhydride (20 ml). The precipitate that formed while hot was
collected and recrystallised from dioxan as white crystals (2.52 g,
CH-pyridine), 8.8 (s, 1H, CH-pyrimidine), 9.0 (s, 1H, CH-triazole)
3.0 (s, 3H, CH3), 3.4 (s, 3H, CH3). MS: m/z (%) 303 (M+, 100). Anal:
calc. for C12H9N5Se (302.2): C, 47.68; H, 2.98; N, 23.17. Found: C,
47.53; H, 3.05; N, 22.91%.
PAPER: 07/4722