June 2009
581
(br s, 1H, COOH). 13C-NMR d: 170.09 (COOH), 165.17 (C-2), 151.20 (C-
10b), 142.79 (C-5), 138.49 (C-6a), 132.90 (C-8), 129.47 (C-7), 128.83 (C-
9), 123.67 (C-10), 117.04 (C-10a), 34.02 (CH2). IR (cmꢀ1): 2922, 1622,
1481, 1368, 1353, 1296, 1255, 1173, 1105, 1019, 968, 927, 908, 774, 715,
641. LC-MS m/z: 261 [MꢄH]ꢄ, 263. EI-MS m/z: (I, %): 261 (8), 260 (12)
[M]ꢄ˙, 218 (15), 217 (35), 216 (100), 215 (77), 189 (7), 184 (10), 183 (4),
171 (17), 130 (5), 129 (17), 102 (10), 75 (5). Anal. Calcd for C11H8N4O2S:
C, 50.76; H, 3.1; N, 21.53; S, 12.32. Found: C, 50.80; H, 3.12; N, 22.00; S,
12.55.
6a), 132.98 (C-8), 129.56 (C-7), 128.89 (C-9), 123.66 (C-10), 117.09 (C-
10a), 61.17 (OCH2), 33.70 (SCH2), 14.53 (CH3). IR (cmꢀ1): 2361, 1719,
1622, 1517, 1478, 1394, 1362, 1306, 1266, 1169, 1026, 901, 768, 715. LC-
MS m/z: 289 [MꢄH]ꢄ. EI-MS m/z (I, %): 289 (10.4), 288 (49.2) [M]ꢄ˙, 243
(18.2), 242 (29.4), 217 (6.8), 216 (24.9), 215 (100.0), 214 (27.1), 202 (15.4),
187 (7.6), 171 (5.0), 130 (12.0), 129 (24.1), 102 (7.5). Anal. Calcd for
C13H12N4O2S: C, 54.15; H, 4.2; N, 19.43; S, 11.12. Found: C, 53.80; H,
4.12; N, 20.08; S, 11.55.
2-([1,2,4]Triazolo[1,5-c]quinazoline-2-ylthio)propionic Acid Methyl
Ester (3c) Compound 3c was obtained as white solid in 52.8% yield
(method A), mp 121—123 °C (2-propanol). 1H-NMR (400 MHz) d: 1.65 (d,
3H, Jꢁ7.2 Hz, SCHCH3), 3.70 (s, 3H, OCH3), 4.62 (q, 1H, Jꢁ7.2 Hz, SCH),
7.81 (t, 1H, Jꢁ7.6 Hz, H-9), 7.94 (t, 1H, Jꢁ7.6 Hz, H-8), 8.04 (d, 1H,
Jꢁ7.8 Hz, H-7), 8.37 (d, 1H, Jꢁ7.8 Hz, H-10), 9.53 (s, 1H, H-5). IR (cmꢀ1):
2360, 1732, 1623, 1514, 1476, 1453, 1392, 1303, 1262, 1173, 1088, 898,
772, 751, 716. LC-MS m/z: 289 [MꢄH]ꢄ, 291. Anal. Calcd for
C13H12N4O2S: C, 54.15; H, 4.2; N, 19.43; S, 11.12. Found: C, 53.23; H,
4.02; N, 20.01; S, 11.67.
3-([1,2,4]Triazolo[1,5-c]quinazoline-2-ylthio)propionic Acid Methyl
Ester (3d) Compound 3d was obtained as white solid in 80.9% yield
(method A), mp 116—118 °C (2-propanolꢀH2O). 1H-NMR (400 MHz) d:
2.89 (m, 2H, CH2COꢄH2O). 3.47 (t, 2H, Jꢁ7.3 Hz, SCH), 3.69 (s, 3H,
OCH3), 7.75 (t, 1H, Jꢁ7.8 Hz, H-9), 7.86 (t, 1H, Jꢁ7.8 Hz, H-8), 8.01 (d,
1H, Jꢁ8.0 Hz, H-7), 8.44 (d, 1H, Jꢁ8.0 Hz, H-10), 9.28 (s, 1H, H-5). IR
(cmꢀ1): 2361, 1729, 1515, 1479, 1398, 1353, 1264, 1174, 901, 770, 717.
LC-MS m/z: 289 [MꢄH]ꢄ, 291. Anal. Calcd for C13H12N4O2S: C, 54.15; H,
4.2; N, 19.43; S, 11.12. Found: C, 53.85; H, 4.24; N, 19.95; S, 11.50.
4-([1,2,4]Triazolo[1,5-c]quinazoline-2-ylthio)butyric Acid Ethyl Ester
(3e) Compound 3e was obtained as white solid in 11.1% yield (method A),
mp 106—108 °C (2-propanol). 1H-NMR (500 MHz) d: 1.16 (t, 3H,
Jꢁ6.8 Hz, CH3), 2.05 (t, 2H, Jꢁ6.8 Hz, SCH2CH2), 3.31 (m, 4H, SCH2,
S(CH2)2CH2COꢄH2O), 4.06 (q, 2H, Jꢁ7.0 Hz, OCH2CH3), 7.80 (t, 1H,
Jꢁ7.2 Hz, H-9), 7.94 (t, 1H, Jꢁ7.2 Hz, H-8), 8.04 (d, 1H, Jꢁ7.8 Hz, H-7),
8.39 (d, 1H, Jꢁ7.8 Hz, H-10), 9.52 (s, 1H, H-5). IR (cmꢀ1): 2361, 1730,
1621, 1516, 1478, 1396, 1250, 1208, 1186, 1136, 1019, 901, 778, 717. LC-
MS m/z: 317 [MꢄH]ꢄ. EI-MS m/z (I, %): 316 (12.1) [M]ꢄ˙, 271 (12.0), 230
(13.3), 229 (100.0), 216 (31.8), 215 (7.0), 203 (6.8), 202 (13.1), 130 (10.3),
129 (51.8), 115 (7.8), 103 (9.0), 102 (53.3), 90 (7.9), 88 (9.8), 87 (13.5).
Anal. Calcd for C15H16N4O2S: C, 56.95; H, 5.10; N, 17.71; S, 10.13. Found:
C, 57.14; H, 5.13; N, 16.95; S, 9.75.
5-([1,2,4]Triazolo[1,5-c]quinazoline-2-ylthio)pentanoic Acid Methyl
Ester (3f) Compound 3f was obtained as white solid in 87.4% yield
(method A), mp 96—98 °C (2-propanolꢀH2O). 1H-NMR (500 MHz) d: 2.49
(m, 4H, CH2CH2COꢄH2O), 2.37 (t, 2H, Jꢁ7.3 Hz, SCH2CH2), 3.29 (t, 2H,
Jꢁ7.3 Hz, SCH2), 3.56 (s, 3H, OCH3), 7.81 (t, 1H, Jꢁ7.3 Hz, H-9), 7.93 (t,
1H, Jꢁ7.3 Hz, H-8), 8.04 (d, 1H, Jꢁ8.1 Hz, H-7), 8.38 (d, 1H, Jꢁ7.8 Hz, H-
10), 9.51 (s, 1H, H-5). IR (cmꢀ1): 2361, 1718, 1617, 1516, 1475, 1386,
1344, 1283, 1220, 1177, 977, 893, 769, 715, 642. LC-MS m/z: 317
[MꢄH]ꢄ. Anal. Calcd for C15H16N4O2S: C, 56.95; H, 5.10; N, 17.71, S,
10.13. Found: C, 57.18; H, 5.23; N, 16.84, S, 9.86.
2-([1,2,4]Triazolo[1,5-c]quinazolin-2-ylthio)propionic Acid (2b)
Compound 2b was obtained as white solid in 73.2% yield, mp 182—184 °C
1
(2-propanolꢀH2O). H-NMR* (400 MHz) d: 1.66 (d, 3H, Jꢁ7.1 Hz, CH3),
4.54 (q, 1H, Jꢁ7.3 Hz, SCH), 7.81 (t, 1H, Jꢁ7.6 Hz, H-9), 7.94 (t, 1H,
Jꢁ7.8 Hz, H-8), 8.03 (d, 1H, Jꢁ7.8 Hz, H-7), 8.38 (d, 1H, Jꢁ7.8 Hz, H-10),
9.52 (s, 1H, H-5). 13C-NMR d: 173.07 (COOH), 165.40 (C-2), 151.15 (C-
10b), 142.83 (C-5), 138.55 (C-6a), 132.95 (C-8), 129.53 (C-7), 128.89 (C-
9), 123.73 (C-10), 117.14 (C-10a), 43.95 (CH), 19.02 (CH3). IR (cmꢀ1):
2360, 1712, 1514, 1478, 1452, 1396, 1354, 1307, 1269, 1248, 1207, 899,
766, 715, 653. LC-MS m/z: 275 [MꢄH]ꢄ, 276. EI-MS m/z (I, %): 275
(14.5) [Mꢄ1]ꢄ˙, 231 (10.6), 230 (83.5), 229 (21.6), 215 (31.9), 202 (9.6),
198 (12.8), 197 (100.0), 171 (31.4), 170 (7.2), 146 (6.9), 145 (5.3), 130
(5.2), 129 (49.0), 103 (5.1), 102 (37.4), 88 (5.5),76 (7.8), 75 (12.1), 60 (5.0).
Anal. Calcd for C12H10N4O2S: C, 52.55; H, 3.67; N, 20.33; S, 11.68. Found:
C, 51.80; H, 3.50; N, 21.07; S, 12.15.
3-([1,2,4]Triazolo[1,5-c]quinazolin-2-ylthio)propionic acid (2c) Com-
pound 2c was obtained as white solid in 68.9% yield, mp 176—178 °C
(2-propanolꢀH2O). 1H-NMR* (400 MHz) d: 2.79 (t, 2H, Jꢁ7.3 Hz,
SCH2CH2), 3.40 (t, 2H, Jꢁ7.3 Hz, SCH2), 7.75 (t, 1H, Jꢁ7.6 Hz, H-9), 7.80
(t, 1H, Jꢁ7.6 Hz, H-8), 8.01 (d, 1H, Jꢁ7.7 Hz, H-7), 8.43 (d, 1H, Jꢁ7.7 Hz,
H-10), 9.27 (s, 1H, H-5). 13C-NMR d: 173.21 (COOH), 165.46 (C-2),
151.27 (C-10b), 142.87 (C-5), 138.60 (C-6a), 132.90 (C-8), 129.47 (C-7),
128.87 (C-9), 123.75 (C-10), 117.17 (C-10a), 34.52 (SCH2), 26.84 (CH2-
COOH). IR (cmꢀ1): 2360, 1710, 1622, 1603, 1517, 1481, 1397, 1357, 1308,
1251, 1209, 1176, 900, 766, 716, 644. LC-MS m/z: 275 [MꢄH]ꢄ, 276.
Anal. Calcd for C12H10N4O2S: C, 52.55; H, 3.67; N, 20.33; S, 11.68. Found:
C, 51.98; H, 3.38; N, 21.10; S, 12.14.
5-([1,2,4]Triazolo[1,5-c]quinazolin-2-ylthio)pentanoic Acid (2d)
Compound 2d was obtained as light yellow solid in 56.6% yield, mp 242—
244 °C (2-propanolꢀH2O). 1H-NMR* (400 MHz) d: 1.80 (m, 6H,
SCH2(CH2)3), 2.60 (t, 2H, Jꢁ7.3 Hz, SCH2), 7.75 (t, 1H, Jꢁ7.6 Hz, H-9),
7.86 (t, 1H, Jꢁ7.6 Hz, H-8), 8.01 (d, 1H, Jꢁ7.7 Hz, H-7), 8.43 (d, 1H,
Jꢁ7.7 Hz, H-10), 9.27 (s, 1H, H-5). IR (cmꢀ1): 2361, 1718, 1618, 1509,
1457, 1282, 1256, 1176, 903, 767, 717. LC-MS m/z: 303 [MꢄH]ꢄ, 304.
Anal. Calcd for C14H14N4O2S: C, 55.62; H, 4.67; N, 18.53; S, 10.60. Found:
C, 54.80; H, 4.87; N, 18.35; S, 10.24.
* Signal of H in COOH group disappeared because of deuterium ex-
change.
General Procedure for the Synthesis of ([1,2,4]Triazolo[1,5-c]quinazo-
line-2-ylthio)carboxylic Acids Esters (3a—l). Method A The appropri-
ate halogenocarboxylic acid ester (6 mmol) was added to a suspension of 1
(6 mmol) in 2-propanol (15 ml). The resulting mixture was heated for 2 h.
After cooling to room temperature five-fold excess of H2O was added. The
crystalline precipitate was filtered, dried and recrystallized from the suitable
solvent.
Method B A solution of an appropriate ester (6 mmol) in 2-propanol
(15 ml) was added to a solution of 1 (6 mmol) in H2O (15 ml). The resulting
mixture was refluxed for 2 h. Further work-up as in method A afforded
proper esters.
([1,2,4]Triazolo[1,5-c]quinazoline-2-ylthio)acetic Acid Methyl Ester
(3a) Compound 3a was obtained as white solid in 73.3% yield (method
A), mp 154—156 °C (2-propanolꢀH2O). 1H-NMR (400 MHz) d: 3.70 (s,
3H, OCH3), 4.25 (s, 2H, SCH2), 7.82 (t, 1H, Jꢁ7.8 Hz, H-9), 7.94 (t, 1H,
Jꢁ7.8 Hz, H-8), 8.05 (d, 1H, Jꢁ8.0 Hz, H-7), 8.37 (d, 1H, Jꢁ8.0 Hz, H-10),
9.52 (s, 1H, H-5). IR (cmꢀ1): 2360, 1737, 1622, 1514, 1478, 1400, 1299,
1265, 1196, 1160, 996, 895, 773, 716. LC-MS m/z: 275 [MꢄH]ꢄ, 276.
Anal. Calcd for C12H10N4O2S: C, 52.55; H, 3.67; N, 20.43; S, 11.69. Found:
C, 53.50; H, 3.51; N, 21.43; S, 12.01.
([1,2,4]Triazolo[1,5-c]quinazoline-2-ylthio)acetic Acid Ethyl Ester
(3b) Compound 3b was obtained as white solid in 76.4% yield (method
B), mp 110—112 °C (2-propanolꢀH2O). 1H-NMR (400 MHz) d: 1.21 (t,
3H, Jꢁ7.1 Hz, CH3), 4.16 (q, 2H, Jꢁ7.0 Hz, OCH2CH3), 4.23 (s, 2H,
SCH2), 7.82 (t, 1H, Jꢁ7.8 Hz, H-9), 7.94 (t, 1H, Jꢁ7.8 Hz, H-8), 8.05 (d,
1H, Jꢁ8.0 Hz, H-7), 8.37 (d, 1H, Jꢁ8.0, H-10), 9.52 (s, 1H, H-5). 13C-NMR
d: 168.87 (CꢁO), 164.88 (C-2), 151.24 (C-10b), 142.85 (C-5), 138.55 (C-
3-Phenyl-2-([1,2,4]triazolo[1,5-c]quinazoline-2-ylthio)propionic Acid
Ethyl Ester (3g) Compound 3g was obtained as white solid in 92.2% yield
(method A), mp 128—130 °C (2-propanolꢀH2O). 1H-NMR (400 MHz) d:
1.16 (t, 3H, Jꢁ7.3 Hz, CH3), 3.32 (d, 2H, Jꢁ7.3 Hz, SCHCH2CO), 4.09 (q,
2
3
2H, Jꢁ7.3 Hz, Jꢁ1.8 Hz, OCH2), 4.73 (t, 1H, Jꢁ7.3 Hz, SCH), 7.20 (m,
1H, 4Ph), 7.28 (m, 4H, H-2Ph,3Ph,5Ph,6Ph), 7.88 (t, 1H, Jꢁ7.8 Hz, H-9), 7.78
(t, 1H, Jꢁ7.8 Hz, H-8), 8.03 (d, 1H, Jꢁ8.0 Hz, H-7), 8.45 (d, 1H, Jꢁ8.2 Hz,
H-10), 9.30 (s, 1H, H-5). IR (cmꢀ1): 2972, 2926, 2352, 1721, 1594, 1515,
1477, 1453, 1369, 1299, 1263, 1239, 1175, 1030, 898, 862, 773, 747, 714,
698, 639. LC-MS m/z: 379 [MꢄH]ꢄ, 381. EI-MS m/z (I, %): 379 (5.6)
[M]ꢄ˙, 204 (8.1), 203 (20.5), 202 (100.0), 129 (11.7), 102 (4.8), 91 (13.2).
Anal. Calcd for C20H18N4O2S: C, 64.47; H, 4.79; N, 14.80; S, 8.47. Found:
C, 64.10; H, 4.57; N, 15.31; S, 7.09.
3-(3-Methylphenyl)-2-([1,2,4]triazolo[1,5-c]quinazoline-2-ylthio)pro-
pionic Acid Ethyl Ester (3h) Compound 3h was obtained as grey solid in
95.7% yield (method B), mp 67—69 °C (2-propanolꢀH2O). 1H-NMR
(400 MHz) d: 1.08 (t, 3H, Jꢁ7.2 Hz, CH2CH3), 2.26 (s, 3H, CH3), 3.26 (d,
2H, Jꢁ7.2 Hz, SCHCH2), 4.09 (q, 2H, Jꢁ7.2 Hz, OCH2CH3), 4.70 (t, 1H,
Jꢁ7.2 Hz, SCH), 7.05 (m, 3H, H-2Ph,4Ph,6Ph), 7.18 (t, 1H, Jꢁ7.6 Hz, H-5Ph),
7.82 (t, 1H, Jꢁ7.8 Hz, H-9), 7,94 (t, 1H, Jꢁ7.8 Hz, H-8), 8.04 (d, 1H,
Jꢁ8.2 Hz, H-7), 8.37 (d, 1H, Jꢁ7.8 Hz, H-10), 9.52 (s, 1H, H-5). IR (cmꢀ1):
2362, 1736, 1623, 1515, 1477, 1391, 1304, 1270, 1172, 1158, 899, 773,
715, 699. LC-MS m/z: 393 [MꢄH]ꢄ. Anal. Calcd for C21H20N4O2S: C,
64.27; H, 5.14; N, 14.27; S, 8.17. Found: C, 63.95; H, 4.72; N, 14.94; S,