Chemistry of Heterocyclic Compounds 2019, 55(8), 768–772
231 (55), 203 (34), 190 (54), 172 (28), 164 (89), 145 (100).
Found, %: С 52.12; Н 3.30; N 21.35; S 8.22. C17H13F3N6S.
Calculated, %: C 52.30; H 3.36; N 21.53; S 8.21.
4,6-Dimethyl-2-[1-(2,4-dimethylphenyl)-1H-tetrazol-
5-yl]thieno[2,3-b]pyridin-3-amine (6b). Yield 0.54 g
(97%) (method I), 3.22 g (92%) (method II), light-beige
powder, mp 249–251°C (decomp.) (method I), 247–250°C
4,6-Dimethyl-2-{[(3,5-dimethyl-1,2-oxazol-4-yl)methyl]-
sulfanyl}pyridine-3-carbonitrile (8). A solution of 4-(chloro-
methyl)-3,5-dimethyl-1,2-oxazole (9) (1.46 g, 10 mmol) in
MeOH (6 ml) was added to a solution of NaOH (0.44 g,
11 mmol) and compound 4 (1.64 g, 10 mmol) in MeOH
(15 ml). The reaction mixture was stirred at 50–60°C for
3 h. H2O (7 ml) was then added, and the mixture was kept
at 5–10°C for 12 h. The formed precipitate was filtered off,
washed with MeOH–H2O, 3:1 mixture (10 ml), and
recrystallized from the same mixture. Yield 1.98 g (73%),
colorless crystals, mp 90–92°C. 1H NMR spectrum, δ, ppm:
2.23 (3H, s, CH3); 2.39 (3H, s, CH3); 2.42 (3H, s, CH3);
2.53 (3H, s, CH3); 4.33 (2H, s, CH2); 7.14 (1H, s, H-5).
13C NMR spectrum, δ, ppm: 10.4; 11.5; 20.2; 22.3; 24.8;
105.2; 109.9; 115.0; 120.5; 152.2; 159.7; 161.0; 161.4;
166.7. Mass spectrum, m/z (Irel, %): 273 [M]+ (16), 164
(78), 142 (13), 110 (44), 68 (100). Found, %: C 61.58;
H 5.61; N 15.26; S 11.69. C14H15N3OS. Calculated, %:
C 61.52; H 5.53; N 15.37; S 11.73.
1
(decomp.) (method II). H NMR spectrum, δ, ppm (J, Hz):
1.88 (3H, s, CH3); 2.44 (3H, s, CH3); 2.48 (3H, s, CH3);
2.77 (3H, s, CH3); 7.00 (2H, br. s, NH2); 7.07 (1H, s, H-5);
7.33 (1H, d, J = 7.9, H-5'); 7.40 (1H, s, H-3'); 7.48 (1H, d,
J = 7.9, H-6'). 13C NMR spectrum, δ, ppm: 16.6; 19.8;
21.0; 23.7; 85.9; 121.5; 121.9; 127.9; 128.6; 129.6; 131.7;
136.0; 142.1; 144.4; 146.1; 151.5; 158.4; 160.1. Mass
spectrum, m/z (Irel, %): 350 [M]+ (48), 322 [M–N2]+ (14),
217 (28), 203 (41), 178 (31), 164 (60), 145 (84), 131 (100).
Found, %: С 61.77; Н 5.24; N 23.89; S 9.14. C18H18N6S.
Calculated, %: C 61.69; H 5.18; N 23.98; S 9.15.
2-[1-(4-Fluorophenyl)-1H-tetrazol-5-yl]-4,6-dimethyl-
thieno[2,3-b]pyridin-3-amine (6c). Yield 3.09 g (91%)
(method II), beige powder, mp 237–239°C (decomp.).
1H NMR spectrum, δ, ppm (J, Hz): 2.43 (3H, s, CH3); 2.76
(3H, s, CH3); 6.95 (2H, br. s, NH2); 7.05 (1H, s, H-5); 7.55
(2H, t, J = 8.3, H-3',5'); 7.82 (2H, dd, J = 8.3, J = 4.3,
H-2',6'). 13C NMR spectrum, δ, ppm (J, Hz): 19.8; 23.7;
2
86.1; 116.7 (d, JCF = 24.3); 121.4; 122.0; 129.4; 130.8 (d,
3JCF = 8.7); 144.3; 146.1; 151.5; 158.4; 159.9; 163.7 (d,
1JCF = 249.7). Found, %: С 56.55; Н 3.83; N 24.60; S 9.35.
C16H13FN6S. Calculated, %: C 56.46; H 3.85; N 24.69;
S 9.42.
References
1. (а) Litvinov, V. P.; Dotsenko, V. V.; Krivokolysko, S. G.
Chemistry of Thienopyridines and Related Systems [in
Russian]; Belen'kii, L. I., Ed.; Nauka: Moscow, 2006, p. 5.
(b) Salem, M. E.; Darweesh, A. F.; Elwahy, A. H. M. J. Sulfur
Chem. 2018, 39, 525. (c) Dyachenko, I. V.; Dyachenko, V. D.;
Dorovatovskii, P. V.; Khrustalev, V. N.; Nenajdenko, V. G.
Russ. J. Org. Chem. 2018, 54, 1435. [Zh. Org. Khim. 2018,
54, 1423.]
2. (a) Rolim Bernardino, A. M.; da Silva Pinheiro, L. C.;
Rodrigues, C. R.; Loureiro, N. I.; Castro, H. C.; Lanfredi-
Rangel, A.; Sabatini-Lopes, J.; Borges, J. C.; Carvalho, J. M.;
Romeiro, G. A.; Ferreira, V. F.; Frugulhetti, I. C. P. P.;
Vannier-Santos, M. A. Bioorg. Med. Chem. 2006, 14, 5765.
(b) Al-Trawneh, S. A.; El-Abadelah, M. M.; Zahra, J. A.;
Al-Taweel, S. A.; Zani, F.; Incerti, M.; Cavazzoni, A.; Vicini, P.
Bioorg. Med. Chem. 2011, 19, 2541.
2-[1-(4-Chlorophenyl)-1H-tetrazol-5-yl]-4,6-dimethyl-
thieno[2,3-b]pyridin-3-amine (6d). Yield 3.36 g (94%)
(method II), light-beige powder, mp 238–239°C (decomp.).
1H NMR spectrum, δ, ppm: 2.43 (3H, s, CH3); 2.75 (3H, s,
CH3); 6.94 (2H, br. s, NH2); 7.04 (1H, s, H-5); 7.78 (4H, s,
H Ar). 13C NMR spectrum, δ, ppm: 19.9; 23.7; 86.0; 121.4;
122.1; 129.8; 130.2; 132.1; 136.6; 144.5; 146.2; 151.4;
158.6; 159.9. Found, %: С 53.77; Н 3.51; N 23.39; S 9.03.
C16H13ClN6S. Calculated, %: C 53.86; H 3.67; N 23.55;
S 8.98.
2-[1-(4-Bromophenyl)-1H-tetrazol-5-yl]-4,6-dimethyl-
thieno[2,3-b]pyridin-3-amine (6e). Yield 3.85 g (96%)
(method II), pink-beige powder, mp 253–255°C (decomp.).
1H NMR spectrum, δ, ppm (J, Hz): 2.47 (3H, s, CH3); 2.79
(3H, s, CH3); 6.89 (2H, br. s, NH2); 6.97 (1H, s, H-5); 7.60
(2H, d, J = 7.9, H-2',6'); 7.85 (2H, d, J = 7.9, H-3',5').
13C NMR spectrum, δ, ppm: 19.9; 23.7; 85.9; 121.4; 122.0;
125.2; 130.2; 132.4; 132.7; 144.4; 146.2; 151.3; 158.5; 159.9.
Found, %: С 47.99; Н 3.41; N 20.88; S 8.05. C16H13BrN6S.
Calculated, %: C 47.89; H 3.27; N 20.94; S 7.99.
3. Chaubey, A.; Pandeya, S. N. Asian J. Pharm. Clin. Res. 2011,
4, 5.
4. (a) Madhusudana, K.; Shireesha, B.; Modi Naidu, V. G.;
Ramakrishna, S.; Narsaiah, B.; Rao, A. R.; Diwan, P. V. Eur.
J. Pharmacol. 2012, 678, 48. (b) Liu, H.; Li, Y.; Wang, X.-Y.;
Wang, B.; He, H.-Y.; Liu, J.-Y.; Xiang, M.-L.; He, J.; Wu, X.-H.;
Yang, L. Bioorg. Med. Chem. Lett. 2013, 23, 2349.
5. (а) Bahekar, R. H.; Jain, M. R.; Goel, A.; Patel, D. N.;
Prajapati, V. M.; Gupta, A. A.; Javad, P. A.; Patel, P. R.
Bioorg. Med. Chem. 2007, 15, 3248. (b) Kamata, M.;
Yamashita, T.; Kina, A.; Funata, M.; Mizukami, A.; Sasaki, M.;
Tani, A.; Funami, M.; Amano, N.; Fukatsu, K. Bioorg. Med.
Chem. Lett. 2012, 22, 3643.
6. Adachi, I.; Yamamori, T.; Hiramatsu, Y.; Sakai, K.; Mihara, S.;
Kawakami, M.; Masui, M.; Uno, O.; Ueda, M. Chem. Pharm.
Bull. 1988, 36, 4389.
7. Pevet, I.; Brulé, C.; Tizot, A.; Gohier, A.; Cruzalegui, F.;
Boutin, J. A.; Goldstein, S. Bioorg. Med. Chem. 2011, 19,
2517.
4,6-Dimethyl-2-{1-[3-(trifluoromethyl)phenyl]-1H-
tetrazol-5-yl}thieno[2,3-b]pyridin-3-amine (6f). Yield
3.67 g (94%) (method II), light-beige powder, mp 254–
1
256°C (decomp.). H NMR spectrum, δ, ppm (J, Hz): 2.44
(3H, s, CH3); 2.78 (3H, s, CH3); 7.00 (2H, br. s, NH2); 7.08
(1H, s, H-5); 7.95 (1H, t, J = 7.9, H-5'); 8.10 (1H, d,
J = 7.9, H-4'); 8.18 (1H, d, J = 7.9, H-6'); 8.33 (1H, s,
H-2'). 13C NMR spectrum, δ, ppm (J, Hz): 19.8; 23.6; 85.7;
121.4; 122.0; 123.3 (q, 1JCF = 272.3); 125.4 (q, 3JCF = 4.3);
8. Herr, R. J. Bioorg. Med. Chem. 2002, 10, 3379.
9. Abdel-Rahman, A. E.; Bakhite, E. A.; Mohamed, O. S.;
Thabet, E. A. Phosphorus, Sulfur Silicon Relat. Elem. 2003,
178, 89.
3
2
128.3 (q, JCF = 4.3); 130.3 (q, JCF = 32.9); 131.0; 132.3;
133.9; 144.4; 146.3; 151.4; 158.5; 159.7. Mass spectrum,
m/z (Irel, %): 390 [M]+ (68), 362 [M–N2]+ (66), 341 (10),
771