L.C. López-Cara et al. / European Journal of Medicinal Chemistry 50 (2012) 129e139
137
(100 MHz)
d
173.12, 151.33, 149.07, 140.20, 119.01, 117.70, 114.48,
3H), 2.09 (s, 6H); 13C NMR (75 MHz)
d
169.88, 148.56, 144.28,
113.08, 78.33, 56.04, 29.77, 29.26, 8.77. MS (LSIMS) m/z 294.1282
131.28, 130.00, 121.78, 117.75, 113.86, 78.66, 29.39, 24.89. MS
(LSIMS) m/z 284.0620 (M þ H)þ, Calcd. Mass for C12H15N3OSCl
284.0624.
(M þ H)þ, Calcd. Mass for C14H20N3O2S 294.1276.
4.1.6.3. 5-(2-Amino-5-methoxyphenyl)-3-butyryl-2,2-dimethyl-2,3-
dihydro-1,3,4-thiadiazole, 9c. (83%); mp 75e77 ꢂC; 1H NMR
4.1.6.11. 5-(2-Amino-5-chlorophenyl)-2,2-dimethyl-3-propyonyl-2,3-
(400 MHz)
2.64 (t, 2H), 2.07 (s, 6H), 1.74 (m, 2H), 1.00 (t, 3H); 13C NMR
(100 MHz) 172.38, 151.36, 149.03, 140.06, 118.97, 117.74, 114.46,
d
6.86 (dd, 1H), 6.72 (d, 1H). 6.70 (d, H-60), 3.77 (s, 3H),
dihydro-1,3,4-thiadiazole, 9k. (82%); mp 166e169 ꢂC; 1H NMR
(300 MHz)
d
7.17 (m, 2H), 6.74 (d, 1H), 5.25 (bs), 2.70 (c, 2H),
173.22, 148.39,
d
2.09 (s, 6H), 1.22 (t, 3H); 13C NMR (75 MHz)
d
113.15, 78.34, 56.03, 38.47, 29.26, 18.13, 13.97. MS (LSIMS) m/z
143.99, 131.26, 130.05, 122.08, 117.93, 114.21, 78.86, 29.92, 29.43,
8.89. MS (LSIMS) m/z 298.0774 (M þ H)þ, Calcd. Mass for
C13H17N3OSCl 298.0781.
330.1250 (M þ Na)þ, Calcd. Mass for C15H21N3O2SNa 330.1252.
4.1.6.4. 5-(2-Amino-5-methoxyphenyl)-2,2-dimethyl-3-pentanoyl-
2,3-dihydro-1,3,4-thiadiazole, 9d. (86%); mp 76e78 ꢂC; 1H NMR
4.1.6.12. 5-(2-Amino-5-chlorophenyl)-3-butyryl-2,2-dimethyl-2,3-
(300 MHz)
2.68 (t, 2H), 2.09 (s, 6H), 1.71 (m, 2H), 1.42 (m, 2H), 0.96 (t, 3H); 13C
NMR (75 MHz) 172.58, 151.64, 149.92, 139.31, 118.84, 118.07,
d
6.89 (dd, 1H), 6.78 (d, 1H), 6.73 (d, 1H), 3.79 (s, 3H),
dihydro-1,3,4-thiadiazole, 9l. (90%); mp 122e124 ꢂC; 1H NMR
(300 MHz)
d
7.16 (m, 2H), 6.72 (d, 1H), 2.64 (t, 2H), 2.09 (s, 6H), 1.75
172.48, 148.33, 144.27,
d
(m, 2H), 1.02 (t, 3H); 13C NMR (75 MHz)
d
114.49, 113.52, 78.39, 56.00, 36.33, 29.25, 26.78, 22.60, 13.98. MS
(LSIMS) m/z 344.1409 (M þ Na)þ, Calcd. Mass for C16H23N3O2NaS
344.1409.
131.25, 130.02, 121.84, 117.76, 114.04, 78.83, 38.63, 29.44, 18.27,
14.15. MS (LSIMS) m/z 334.0758 (M þ Na)þ, Calcd. Mass for
C14H18N3OSClNa 334.0757.
4.1.6.5. 5-(2-Amino-5-methoxyphenyl)-3-cyclopropylcarbonyl-2,2-
4.1.6.13. 5-(2-Amino-5-chlorophenyl)-2,2-dimethyl-3-pentanoyl-2,3-
dimethyl-2,3-dihydro-1,3,4-thiadiazole, 9e. (80%); mp 100e102 ꢂC;
dihydro-1,3,4-thiadiazole, 9m. (79%); mp 110e112 ꢂC; 1H NMR
1H NMR (400 MHz)
d
6.87 (dd, 1H), 6.73 (d, 1H), 6.72 (d, 1H), 3.77 (s,
3H), 2.37 (m, 1H), 2.06 (s, 6H), 1.07 (m, 2H), 0.88 (m, 2H); 13C NMR
(100 MHz) 172.72, 151.55, 149.20, 139.75, 118.88, 117.90, 114.53,
(400 MHz)
1.98 (s, 6H), 1.60 (m, 2H), 1.32 (m, 2H), 0.87 (t, 3H); 13C NMR
(100 MHz) 172.67, 148.36, 144.53, 131.24, 130.02, 121.62, 117.61,
d 7.06 (m, 2H), 6.60 (d, 1H), 5.50 (bs, 2H), 2.56 (t, 2H),
d
d
113.70, 78.55, 56.04, 29.28, 13.86, 8.52. MS (LSIMS) m/z 328.1096
113.87, 78.77, 36.51, 29.43, 26.94, 22.79, 14.16. MS (LSIMS) m/z
(M þ Na)þ, Calcd. Mass for C15H19N3O2SNa 328.1096.
326.1094 (M þ H)þ, Calcd. Mass for C15H21N3OSCl 326.1094.
4.1.6.6. 5-(2-Amino-5-methoxyphenyl)-3-cyclobutanecarbonyl-2,2-
4.1.6.14. 5-(2-Amino-5-chloro)-3-cyclopropylcarbonyl-2,2-dimethyl-
dimethyl-2,3-dihydro-1,3,4-thiadiazole, 9f. (82%); mp 156e159 ꢂC;
2,3-dihydro-1,3,4-thiadiazole, 9n. (79%); mp 187e190 ꢂC; 1H NMR
1H NMR (400 MHz)
d
6.84 (dd, 1H), 6.69 (d, 1H), 6.68 (d, 1H, H-60),
(400 MHz)
1.05 (m, 2H), 0.87 (m, 2H); 13C NMR (100 MHz)
144.37,131.19,129.98,121.72,117.67,114.12, 78.92, 29.40, 14.02, 8.76.
d
7.13 (m, 2H), 6.68 (m, 1H), 2.31 (m, 1H), 2.04 (s, 6H),
3.74 (s, 3H), 3.66 (m, 1H), 2.29 (m, 4H), 2.05 (s, 6H), 1.94 (m, 2H); 13C
NMR (100 MHz) 174.10, 151.43, 149.23, 140.25, 119.09, 117.82,
d
172.79, 148.61,
d
114.57,113.24, 78.33, 56.17, 40.10, 29.31, 24.81,18.15. MS (LSIMS) m/z
MS (LSIMS) m/z 332.0594 (M
C14H16N3OSClNa 332.0600.
þ
Na)þ, Calcd. Mass for
342.1253 (M þ Na)þ, Calcd. Mass for C16H21N3O2SNa 342.1252.
4.1.6.7. 5-(2-Amino-5-methoxyphenyl)-3-cyclopentanecarbonyl-2,2-
4.1.6.15. 5-(2-Amino-5-chlorophenyl)-3-cyclobutanecarbonyl-2,2-
dimethyl-2,3-dihydro-1,3,4-thiadiazole, 9g. (91%); mp 157e159 ꢂC;
dimethyl-2,3-dihydro-1,3,4-thiadiazole, 9o. (80%); mp 162e164 ꢂC;
1H NMR (300 MHz)
d
6.83 (dd, 1H), 6.69 (d, 1H), 6.68 (d, 1H, H-60),
1H NMR (300 MHz)
d
7.15 (m, 2H), 6.69 (d, 1H), 5.52 (bs, 2H), 3.66
3.74 (s, 3H), 3.34 (m, 1H), 2.04 (s, 6H), 1.94e1.53 (3m, 8H); 13C NMR
(75 MHz) 175.48, 151.36, 148.67, 140.03, 118.89, 117.70, 114.49,
(m, 1H), 2.39, 2.24, 1.95(3m, 6H), 2.09 (s, 6H); 13C NMR (75 MHz)
d
d 174.04, 148.42, 144.40, 131.19, 129.97, 121.61, 117.58, 113.91, 78.63,
113.29, 78.31, 56.02, 44.50, 29.93, 29.19, 26.18. MS (LSIMS) m/z
40.09, 29.32, 24.78, 18.14. MS (LSIMS) m/z 346.0755 (M þ Na)þ,
334.1582 (M þ H)þ, Calcd. Mass for C17H24N3O2S 334.1589.
Calcd. Mass for C15H18N3OSClNa 346.0757.
4.1.6.8. 5-(2-Amino-5-methoxyphenyl)-3-cyclohexanecarbonyl-2,2-
4.1.6.16. 5-(2-Amino-5-chlorophenyl)-3-cyclopentanecarbonyl-2,2-
dimethyl-2,3-dihydro-1,3,4-thiadiazole, 9h. (65%); mp 124e125 ꢂC;
dimethyl-2,3-dihydro-1,3,4-thiadiazole, 9p. (77%); mp 174e177 ꢂC;
1H NMR (300 MHz)
d
6.79 (dd, 1H), 6.68 (d, 1H), 6.63 (d, 1H), 3.69 (s,
3H), 2.82 (m, 1H), 1.97 (s, 6H), 1.88e1.21 (5m, 10H); 13C NMR
(75 MHz) 175.59, 151.70, 148.32, 140.08, 118.85, 118.59, 114.75,
1H NMR (300 MHz)
d
7.15 (m, 2H), 6.70 (d, 1H), 5.55 (bs, 2H),3.35
(m, 1H), 2.08 (s, 6H), 1.91, 1.75, 1.63 (3m, 8H); 13C NMR (75 MHz)
d
d 175.58, 148.05, 144.40, 131.16, 129.98, 121.64, 117.60, 114.02, 78.75,
114.22, 78.69, 56.16, 44.39, 29.40, 28.86, 26.20. MS (LSIMS) m/z
44.64, 29.81, 29.35, 26.34. MS (LSIMS) m/z 360.0916 (M þ Na)þ,
370.1567 (M þ Na)þ, Calcd. Mass for C18H25N3O2SNa 370.1565.
Calcd. Mass for C16H20N3OSClNa 360.0913.
4.1.6.9. 5-(2-Amino-5-methoxyphenyl)-3-benzoyl-2,2-dimethyl-2,3-
4.1.6.17. 5-(2-Amino-5-chlorophenyl)-3-cyclohexanecarbonyl-2,2-
dihydro-1,3,4-thiadiazole, 9i. (95%); mp 125e127 ꢂC; 1H NMR
dimethyl-2,3-dihydro-1,3,4-thiadiazole, 9q. (80%); mp 172e175 ꢂC;
(300 MHz)
1H), 6.58 (d, 1H, H-30), 4.54 (bs, 2H), 3.77 (s, 3H), 2.22 (s, 6H); 13C
NMR (75 MHz) 168.87, 151.23, 149.68, 140.32, 136.86, 130.79,
d
7.74 (dd, 2H), 7.44 (m, 3H), 6.83 (dd, 1H, H-40), 6.72 (d,
1H NMR (300 MHz)
d
7.06 (m, 2H), 6.60 (d, 1H), 5.48 (bs, 2H), 2.78
(m, 1H), 1.97 (s, 6H), 1.89e1.14 (5m, 10H); 13C NMR (75 MHz)
d
d 175.49, 148.20, 144.45, 131.18, 129.98, 121.64, 117.61, 113.95, 78.81,
128.64, 128.04, 119.32, 117.73, 114.62, 112.80, 79.05, 56.17, 28.92. MS
(LSIMS) m/z 364.1101 (M þ Na)þ, Calcd. Mass for C18H19N3O2SNa
364.1096.
44.47, 29.38, 28.82, 26.22, 26.17. MS (LSIMS) m/z 352.1251 (M þ H)þ,
Calcd. Mass for C17H23N3OSCl 352.1250.
4.1.6.18. 5-(2-Amino-5-chlorophenyl)-3-benzoyl-2,2-dimethyl-2,3-
4.1.6.10. 3-Acethyl-5-(2-amino-5-chlorohenyl)-2,2-dimethyl-2,3-
dihydro-1,3,4-thiadiazole, 9r. (77%); mp 106e108 ꢂC; 1H NMR
dihydro-1,3,4-thiadiazole, 9j. (87%); mp 194e197 ꢂC; 1H NMR
(300 MHz)
d
7.74 (dd, 2H), 7.45 (m, 3H), 7.12 (m, 2H), 6.56 (d, 1H. H-
168.87, 148.84,
(300 MHz)
d
7.16 (m, 2H), 6.72 (d, 1H), 5.32 (bs, 2H), 2.37 (s,
30), 5.25 (bs, 2H), 2.22 (s, 6H); 13C NMR (75 MHz)
d