Pyrimidinones and pyrimidinethiones
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 4, April, 2004
881
m/z (Irel (%)): 262 [M + H]+ (77), 260 [M – H]+ (100), 225
[M – HCl]+ (20).
was 85%. MS, m/z (Irel (%)): 313 [M]+ (61), 267 [M – SCH2]+
(50), 240 [M – COOEt]+ (100).
3ꢀCyanoꢀ4ꢀdimethylaminoꢀ2ꢀmethylthiopyridine (19). A mixꢀ
ture of enamine 14 (0.8 g, 4.73 mmol) and acetal 3b (12.31 mmol)
in dry toluene (5 mL) was refluxed with stirring for 14 h, argon
being passed through the reaction medium. The reaction mixꢀ
ture was concentrated in vacuo, 90% aqueous AcOH (10 mL)
was added to the oily residue, the mixture was kept for 24 h, and
water (20 mL) was added. The black solid precipitate that formed
was filtered off, washed with water, dried, and extracted with
hexane. Compound 19 was obtained in a yield of 0.45 g (46%).
MS, m/z (Irel (%)): 193 [M]+ (100), 178 [M – Me]+ (28), 165
(22), 132 [M – SMe – CH2]+ (30).
3ꢀCyanoꢀ2ꢀethylthioꢀ4ꢀformylanilinopyridine (20). Boron
trifluoride etherate (0.50 mL) was added with stirring and coolꢀ
ing to 0—5 °C to a solution of triethyl orthoformate (0.51 mL) in
CH2Cl2 (3 mL). Then a solution of compound 13a (0.3 g,
1.06 mmol) in CH2Cl2 (5 mL) was added. The reaction mixture
was refluxed with stirring for 2 h and concentrated in vacuo at
20 °C. The resulting oil was triturated successively in hexane
(2×10 mL) and a concentrated Na2CO3 solution (~15 mL) and
kept for 2 days. The precipitate that formed was filtered off,
washed with water and diethyl ether, and dried. Technical prodꢀ
uct 20 containing ~10% of compound 21a was obtained in a
yield of 0.20 g. After crystallization from hexane, analytically
pure compound 20 was obtained in a yield of 0.12 g as white
crystals. 13C NMR (DMSOꢀd6), δ: 14.6, 24.8 (Et); 105.7 (C(3));
113.9 (CN); 119.0 (C(5)); 124.9, 128.3, 130.4 (Ph); 139.6
(C(1´)); 150.8 (C(4)); 154.3 (C(6)); 162.3 (CHO); 164.5 (C(2)).
The assignment of the signals in the 13C NMR spectrum was
made based on HMBS and HSQC experiments. The characterꢀ
istic correlation peaks in the HMBS spectrum are as follows:
C(2)/CH2 = 164.5/3.26 ppm, C(4)/CHO = 150.8/8.78 ppm.
IR, ν/cm–1: 1691, 1700 (CO), 2227 (CN). MS, m/z (Irel (%)):
283 [M]+ (46), 255 [M – CO]+ (80), 254 [M – CHO]+ (93), 226
[M – CO – Et]+ (100), 194 [M – CO – SEt]+ (41).
2ꢀAlkylthioꢀ4ꢀanilinoꢀ3ꢀcyanopyridines (21a—d) (general
procedure). The corresponding alkylating agent (1.60 mmol) was
added to a mixture of pyridinethione 16a (0.30 g, 1.32 mmol),
K2CO3 (0.3 g), PriOH (6 mL), and water (2 mL). The reaction
mixture was stirred at 20 °C for 24 h. Then water (10—15 mL)
was added and the mixture was stirred. The precipitate that
formed was filtered off, thoroughly washed with water and hexꢀ
ane, and dried. Compounds 21a—d were obtained as white
crystals.
4ꢀAnilinoꢀ3ꢀcyanoꢀ2ꢀethylthiopyridine (21a). 13C NMR
(DMSOꢀd6), δ: 14.8, 23.9 (Et); 91.3 (C(3)); 104.7 (C(5)); 115.1
(CN); 123.7, 125.4, 129.6 (Ph); 138.7 (C(1´)); 151.3 (C(6));
154.1 (C(4)); 163.6 (C(2)). The assignment of the signals in the
13C NMR spectrum was made based on Dept experiments.
Compound 21a was also synthesized independently. A mixꢀ
ture of compound 20 (0.10 g) and piperidine (0.10 g) in MeOH
(2.5 mL) was refluxed with stirring for 3.5 h. After cooling,
water (10 mL) was added. The precipitate that formed was filꢀ
tered off, washed with water and diethyl ether, and dried. Comꢀ
pound 21a was obtained in a yield of 0.09 g (100%).
4ꢀAnilinoꢀ2ꢀcyanomethylthioꢀ3ꢀcyanopyridine (21d) was synꢀ
thesized according to the general procedure. The yield was 91%.
MS, m/z (Irel (%)): 266 [M]+ (100), 194 [M – SCH2CN]+ (29).
1ꢀAcetylꢀ3ꢀaminoꢀ4ꢀanilinothieno[2,3ꢀb]pyridine (22).
Chloroacetone (0.20 mL) was added to a solution of compound
16a (0.3 g, 1.32 mmol) and K2CO3 (0.2 g) in 75% aqueous
PriOH (8 mL). The reaction mixture was stirred at 20 °C for 20 h
and then water (10 mL) was added. The precipitate that formed
was filtered off, washed with diethyl ether, and dried. Comꢀ
1
pound 22 was obtained in a yield of 0.34 g (91%). H NMR, δ:
2.21 (s, 3 H, Me); 6.64 (d, 1 H, H(5), 3JH,H = 5.6 Hz); 7.00—7.70
(m, 5 H, Ph); 7.76 (br.s, 2 H, NH2); 8.10 (d, 1 H, H(6), 3JH,H
=
5.6 Hz); 8.37 (br.s, 1 H, NH). IR, ν/cm–1: 3360, 3289, 3156
(NH, NH2); 1604 (CO). MS, m/z (Irel (%)): 283 [M]+ (66), 268
[M – Me]+ (100), 240 [M – COMe]+ (41).
4ꢀAcetylꢀ1ꢀphenylꢀ5ꢀthiaꢀ1,3,6ꢀtriazaacenaphthene (23).
Acetal 3b (1.15 mmol) was added to a solution of compound 22
(0.25 g, 0.882 mmol) in MeOH (5 mL) at 40 °C for 6 h. The
precipitate that formed was filtered off, washed with hexane,
and dried. Compound 23 was obtained in a yield of 0.22 g
(85%). 1H NMR, δ: 2.67 (s, 3 H, Me); 6.24 (d, 1 H, H(8),
3JH,H = 6.0 Hz); 7.55—7.65 (m, 5 H, Ph); 7.97 (br.s, 1 H, H(2));
8.27 (d, 1 H, H(7), 3JH,H = 6.0 Hz). IR, ν/cm–1: 1627 (CO).
MS, m/z (Irel (%)): 293 [M]+ (90), 278 [M – Me]+ (100), 250
[M – COMe]+ (46).
References
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4ꢀAnilinoꢀ3ꢀcyanoꢀ2ꢀmethylthiopyridine (21b) was syntheꢀ
sized according to the general procedure. The yield was 87%.
MS, m/z (Irel (%)): 241 [M]+ (100), 194 [M – SMe]+ (54).
4ꢀAnilinoꢀ3ꢀcyanoꢀ2ꢀethoxycarbonylmethylthiopyridine (21c)
was synthesized according to the general procedure. The yield
Received September 12, 2003;
in revised form November 28, 2003