Medicinal Chemistry Research
1-(6-Methyl-4-(pyridin-3-yl)-2-((-3,4,5-trihydroxy-6-
(hydroxymethyl)-β-D-glucopyranosyl thio)-1,4-
dihydropyrimidin-5-yl)ethan-1-one (6a)
reaction mixture was poured into crushed ice/HCl. The
formed solid product was collected by filtration, washed,
dried, and crystallized from proper solvent.
Yield: 66%, M.p., 164–166 °C, C18H23N3O6S (409.13):
Anal. Found: C, 59.89; H, 4.93; N, 5.28% Calcd.: C, 60.06;
H, 5.02; N, 5.36% IR (KBr, cm−1):3430-3196, v OH, NH
Ethyl-7-methyl-2-oxo-5-(thiophen-2-yl)-2,3-dihydro-5H-
thiazolo[3,2-a]pyrimidine-6-carboxylate (7a)
1
1690-1675, v CO; H NMR (300 MHz, DMSO): δ 11.30
Yield: 81%, M.p., 165–167 °C, Anal. Found: C, 52.02; H,
4.31; N, 8.56% Calc. C14H14N2O3S2 (322.40): C, 52.16; H,
4.38; N, 8.69% IR (KBr, cm−1):1724-1703, v CO 1649, v C
= N; 1H NMR (300 MHz, DMSO): 7.35-6.88 (m, 3H,
thiophene H), 5.42 (s, 1H, CH), 4.02–4.10 (q, 2H,
CH3CH2), 2.22 (s, 3H, CH3), 2.72 (s, 2H, COCH2), 1.16 (t,
3H, CH3CH2) ppm; 13CNMR:191.0, 172.5 (2CO), 156.5,
153.2, 118.5 (pyrimidine C), 135.5, 127.2, 126.5, 122.5
(thiophene C), 63.5, 61.2 (2 OCH2), 48.7 (methine), 18.0
(CH3), 14.5 (CH3); MS: m/z = 322 (M+, 35%).
(brs, 1H, NH), 7.48-7.07 (m, 4H, pyridine H), 5.10 (s, 1H,
CH), 4.80 (s, 2H, CH2), 4.91–5.22 (m, 4H, 4 OH), 3.60-
4.32 (m, 5H, 5 CH glucose), 2.70 (s, 3H, CH3CO), 2.18 (s,
3H, CH3) ppm; 13C NMR: 191.5 (COCH3), 157.3, 158.5,
110.3 (pyrimidine C), 152.5, 148.2, 133.5, 132.3, 122.5
(pyridine C), 79.3, 77.5, 72.5, 67.3, 64.2 (glucose C), 65.5
(OCH2), 47.3 (methine), 23.2 (CH3CO), and 20.2 (CH3).
Phenyl(6-phenyl-4-(thiophen-2-yl)-2-((-3,4,5-trihydroxy-6-
(hydroxymethyl)-β-D-glucopyranosyloxy)-1,4-
dihydropyrimidin-5-yl)methanone (6b)
Ethyl 7-methyl-2,3-dioxo-5-(thiophen-2-yl)-2,3-dihydro-5H-
thiazolo[3,2-a] pyrimidine-6-carboxylate (7b)
Yield: 65%, M.p., 164–166 °C, C27H26N2O7S (522.15):
Anal. Found: C, 59.89; H, 4.93; N, 5.28%Calcd.: C, 60.06;
H, 5.02; N, 5.36% IR (KBr, cm−1): 3430-3196, v OH, NH
Yield: 79%, M.p., 182–184 °C, C14H12N2O4S2 (336.38):
Anal. Found: C, 49.86; H, 3.44; N, 8.15% Calc. C: 49.99;
H: 3.60; N: 8.33% IR (KBr, cm−1):1722-1703 v (CO), v
1
1690-1675, v CO; H NMR (300 MHz, DMSO): δ11.12
1
(brs, 1H, NH), 7.98-6.99 (m, 13H, ArH), 5.03 (s, 1H, CH),
4.75 (s, 2H, CH2), 4.82–5.18 (m, 4H, 4 OH), 3.70–4.45 (m,
5H, 5 CH glucose) ppm;13CNMR:188.5 (COC6H5), 154.3,
153.5, 110.5 (pyrimidine C), 138.7, 136.5, 133.2, 132.5,
128.5, 128.0, 127.5, 126.3, 125.5, 123.5, 122.8, 121.5
(phenyl and thiazole C), 79.5, 74.3, 73.5, 68.8, 65.5 (glu-
cose C), 62.8 (OCH2), and 48.5 (methine).
1646 (C = N); H NMR (300 MHz, DMSO): 7.36-6.88 (m,
3H, thiophene H), 5.41 (s, 1H, CH), 4.03–4.09 (q, 2H,
CH3CH2), 2.22 (s, 3H, CH3), 2.85 (s, 2H, COCH2), 1.17 (t,
3H, CH3CH2) ppm; 13C NMR: 189.5, 175.3, 167.5 (3CO),
157.6, 148.5, 116.0 (pyrimidine C), 134.4, 128.5, 125.5,
121.5 (thiophene C), 62.3 (OCH2), 51.3 (methine), 18.5
(CH3), 14.2 (CH3); MS: m/z = 336 (M+, 82%).
Phenyl(6-phenyl-4-(thiophen-2-yl)-2-(((2S,3R,4S,5S,6R)-3,4,5-
trihydroxy-6-(hydroxymethyl) -β-D-glucopyranosylthio)-1,4-
dihydropyrimidin-5-yl)methanone (6c)
General procedures for synthesis of pyrimidines 8a,b
The same procedures described before for synthesis of 4a–g.
Yield: 68%, M.p., 152–153 °C, C27H26N2O6S2 (538.12):
Anal. Found: C, 6.11; H, 4.79; N, 5.15% Calc.: C, 60.21; H,
4.87; N, 5.20% IR (KBr, cm−1): 3413-3218, v OH, NH 1687-
1676, v CO; 1H NMR (300 MHz, DMSO): δ 10.75 (brs, 1H,
NH), 8.02-6.97 (m, 13H, ArH), 4.94 (s, 1H, CH), 4.65 (s, 2H,
CH2), 4.73–5.32 (m, 4H, 4 OH), 4.03–4.48 (m, 5H, 5 CH
glucose) ppm; 13C NMR: 191.0 (COC6H5), 154.5, 148.3,
112.5 (pyrimidine C), 139.2 136.5, 133.5, 129.5, 128.2,
127.5, 127.0, 126.3, 125.8, 123.3, 122.5, 121.4 (phenyl and
thiazole C), 80.5, 75.2, 72.5, 68.5, 65.5 (glucose C), 62.5
(OCH2), 49.5 (methine); MS: m/z = 538 (M+, 12%).
4-Oxo-6-(thiophen-2-yl)-2-thioxo-1,2,3,4-
tetrahydropyrimidine-5-carbonitrile (8a)
Yield: 84%, M.p., 121–122 °C, C9H5N3OS2 (235.29): Anal.
Found: C, 45.85; H, 2.19; N, 18.01% Calc. C, 45.94; H,
2.14; N, 17.86% IR (KBr, cm−1): 3440-3230, v NH 2259, v
C≡N 1683, v CO; 1H NMR (300 MHz, DMSO): 12.82, 8.35
(2brs, 2H, 2NH), 7.90-7.13 (m, 3H, thiophene-H) ppm; 13C
NMR: 178.5 (CS), 172.2 (CO), 160.0, 111.5 (pyrimidine C),
133.5, 128.8, 123.5, 122.2 (thiophene C), 116.5 (CN).
4-Oxo-6-(pyridin-3-yl)-2-thioxo-1,2,3,4-
tetrahydropyrimidine-5-carbonitrile (8b)
Synthesis of 7a,b
A
mixture of pyrimidine 4a (1 mmol) and chlor-
Yield: 82%, M.p., 96–97 °C, C10H6N4OS (230.25): Anal.
Found: C, 52.01; H, 2.56; N, 24.18% Calc. C, 52.16; H,
2.63; N, 24.33% IR (KBr, cm−1): 3394-3102, v NH 2215, v
oacetylchloride or oxaloyl chloride (1 mmol) in pyridine
(2 mL) was heated under reflux for 4 h. After cooling, the