188
Med Chem Res (2018) 27:186–193
NMR δ (CDCl3, 200 MHz, ppm, J H–H = Hz); 7.26–7.34
(m, 2H, Ar); 7.02–7.12 (m, 2H, Ar); 5.86 (s, 1H, H-2);
3.75–3.88 (m, 2H, H-5a, H-6a); 3.71 (d, 1H, J = 15.5, H-
32.9 (C-5); 22.7 (C-7); 9.3 (2C). MS (70 eV): m/z (%) =
310 (M+, 0.5); 281 (2); 182 (1); 109 (10); 86 (100); 72 (10).
2
5b); 2.65–2.88 (m, 2H, H-6b, H-7a); 2.46–2.60 (m, 5H, H-
7b, H-8); 1.74–1.80 (m, 4H). 13C NMR δ (CDCl3, 50 MHz,
ppm, J C–F = Hz); 171.3 (C-4); 162.9 (d, 1J = 247.7,
Ar),135.3 (d, 4J = 3.2, Ar), 129.1 (d, 2C, 3J = 8.5, Ar),
2-(4-Fluorophenyl)-3-(3-(piperidin-1-yl)propyl)thiazolidin-
4-one (4Da) It was obtained as an oil; 1H NMR δ (CDCl3,
3
4
500 MHz, ppm, J H–H = Hz); 7.23 (dd, 2H, J = 8.6, J =
5.1, Ar); 7.00 (t, 2H, 3J = 8.5, Ar); 5.64 (d, 1H, 4J = 1.7, H-
2); 3.72 (dd, 1H, 2J = 15.6, 4J = 1.8, H-5a); 3.62 (d, 1 H, 2J
= 15.6, H-5b); 3.57 (ddd, 1H, 2J = 14.1, 3J = 8.0, 3J = 6.6,
2
116.0 (d, 2C, J = 21.8, Ar); 63.2 (C-2); 54.0 (2C, C-8);
52.9 (C-7); 41.2 (C-6); 32.9 (C-5); 23.4 (2C). MS (70 eV):
m/z (%) = 294 (M+, 2); 292 (M − 4, 0.5); 224 (0.5); 153
(1); 139 (2); 97 (6); 84 (100); 69 (3).
2
3
3
H-6a); 2.63 (ddd, 1H, J = 13.9, J = 8.0, J = 5.9, H-6b);
2.18–2.23 (m, 5H, H-8a); 2.10–2.16 (m, 1H, H-8b);
1.60–1.66 (m, 1H, H-7a); 1.52–1.57 (m, 1H, H-7b);
1.45–1.49 (m, 4H); 1.34 (sl, 2H). 13C NMR δ (CDCl3, 125
2-Butyl-3-(2-(pyrrolidin-1-yl)ethyl)thiazolidin-4-one
1
1
MHz, ppm, JC–F = Hz); 171.0 (C-4); 162.9 (d, J = 248.0,
(4Bb) It was obtained as an oil; H NMR δ (CDCl3, 400
4
3
MHz, ppm, J H–H = Hz); 4.70 (td, 1H, 3J = 8.5, 4J = 2.3, H-
Ar); 135.3 (d, J = 6.4, Ar); 128.9 (d, 2C, J = 8.2, Ar);
2
2); 3.77 (ddd, 1H, 2J = 14.2, 3J = 8.2, 3J = 6.0, H-6a); 3.51
115.9 (d, 2C, J = 21.8, Ar); 62.9 (C-2); 56.0 (C-8); 54.3
2
4
2
(2C); 41.2 (C-6); 32.8 (C-5); 25.7 (2C); 24.2; 23.9 (C-7).
MS (70 eV): m/z (%) = 322 (M+, 2); 238 (1); 182 (1.5); 127
(4); 112 (4.5); 98 (100); 84 (9).
(dd, 1H, J = 15.5, J = 1.5, H-5a); 3.42 (d, 1H, J = 15.5,
2
3
3
H-5b); 3.10 (ddd, 1H, J = 13.9, J = 7.9, J = 6.0, H-6b);
2.69 (ddd, 1H, 2J = 12.0, 3J = 8.4, 3J = 5.9, H-7a);
2.50–2.56 (m, 5H); 1.82–1.90 (m, 1H); 1.72 (br, 4H);
1.55–1.65 (m, 1H); 1.25–1.31 (m, 4H); 0.84–0.87 (m, 3H).
13C NMR δ (CDCl3, 100 MHz, ppm); 171.1 (C-4); 61.9 (C-
2); 54.1 (2C); 53.0 (C-7); 41.4 (C-6); 35.3; 32.0 (C-5); 26.2;
23.4 (2C); 22.3; 14.0; MS (70 eV): m/z (%) = 256 (M+, 1);
252 (M − 4, 2); 102 (1); 97 (9); 84 (100); 69 (3).
General procedure for the synthesis of hydrochloride salt
5Aa–f, 5Ba–d, and 5Ca–Ga
In a solution of thiazolidinone 4 in dichloromethane (20 ml)
was flowing the hydrochloric acid (HCl (g)) (generate for the
reaction of H2SO4 concentrated with NaCl) in an open
vessel at room temperature for 30 min. The hydrochloride
salt was filtered off under vacuum. When necessary, the salt
was extracted with distilled water from the organic layer.
2-Phenyl-3-(2-(pyrrolidin-1-yl)ethyl)thiazolidin-4-one
1
(4Bc) It was obtained as an oil; H NMR δ (CDCl3, 400
MHz, ppm, J H–H = Hz); 7.27–7.33 (m, 3H, Ar); 7.20–7.24
(m, 2H, Ar); 5.78 (d, 1H, 4J = 1.6, H-2); 3.74 (dt, 1H, 2J =
3
2
4
13.7, J = 6.7, H-6a); 3.72 (dd, 1H, J = 15.5, J = 1.9, H-
4-(2-(Piperidin-1-yl)ethyl)-1-thia-4-azaspiro[4.5]decan-3-
one chlorohydrate (5Ad) It was obtained as a brown solid;
1H NMR δ (D2O, 400 MHz, ppm, J H–H = Hz); 3.59 (t, 2H,
3J = 6.8, H-6); 3.48–3.52 (m, 2H); 3.48 (s, 2H, H-5); 3.12
5a); 3.64 (d, 1H, 2J = 15.4, H-5b); 2.72–2.79 (m, 2H, H-6b,
2
3
H-7a); 2.61 (dt, 1H, J = 13.5, J = 6.8, H-7b); 2.37–2.40
(m, 4H); 1.65–1.69 (m, 4H). 13C NMR δ (CDCl3, 100 MHz,
ppm); 171.3 (C-4); 139.6 (Ar); 129.1 (Ar); 129.0 (2C, Ar);
127.0 (2C, Ar); 64.0 (C-2); 54.1 (2C); 53.1 (C-7); 41.6 (C-
6); 32.9 (C-5); 23.4 (2C); MS (70 eV): m/z (%) = 276 (M+,
1); 272 (M-4, 2); 178 (0.5); 135 (2); 121 (3); 97 (10); 84
(100); 70 (3).
3
2
4
(t, 2H, J = 6.8, H-7); 2.83 (dt, 2H, J = 12.4, J = 2.3);
1.74–1.83 (m, 4H); 1.63–1.70 (m, 5H); 1.28–1.60 (m, 6H);
0.93–1.04 (m, 1H); 13C NMR δ (D2O, 100 MHz, ppm);
175.1 (C-4); 75.2 (C-2); 55.8 (C-7); 53.9 (2C); 37.1 (2C);
36.4 (C-6); 30.6 (C-5); 23.7; 23.0 (2C); 22.9 (2C); 21.0. MS
(70 eV) (free base 4Ad): m/z (%) = 171 (M+-111, 0.5); 128
(2); 111 (6); 98 (100); 84 (2).
3-(3-(Diethylamino)propyl)-2-(4-fluorophenyl)thiazolidin-
4-one (4Ca) It was obtained as an oil; 1H NMR δ (CDCl3),
3
4
600 MHz, ppm, JH–H = Hz); 7.35 (dd, 2H, J = 8.6, J =
4-(2-(Pyrrolidin-1-yl)ethyl)-1-thia-4-azaspiro[4.5]decan-3-
one chlorhydrate (5Bd) It was obtained as a dark brown
solid; 1H NMR δ (D2O, 400 MHz, ppm, J H–H = Hz);
3.60–3.66 (m, 2H); 3.58 (t, 2H, 3J = 6.8, H-6); 3.49 (s, 2H,
H-5); 3.25 (t, 2H, 3J = 6.7, H-7); 2.96–3.03 (m, 2H);
1.94–2.06 (m, 2H); 1.83–1.91 (m, 2H); 1.75–1.82 (m, 2H);
3
5.2, Ar); 7.08 (t, 2H, J = 8.5, Ar); 5.75 (s, 1H, H-2); 3.79
2
4
2
(dd, 1H, J = 15.6, J = 1.5, H-5a); 3.72 (d, 1H, J = 15.6,
H-5b); 3.62 (dt, 1H, 2J = 14.2, 3J = 7.6, H-6a); 2.78 (q, 4H,
3J = 7.2); 2.74–2.76 (m, 1H, H-6b); 2.65–2.70 (m, 1H, H-
8a); 2.59–2.63 (m, 1H, H-8b); 1.75–1.82 (m, 2H, H-7); 1.12
(t, 6H, 3J = 7.2). 13C NMR δ (CDCl3, 150 MHz, ppm, JC–F
2
1.64–1.71 (m, 4H); 1.49 (d, 1H, J = 13.0); 1.32–1.44 (m,
1
4
= Hz); 171.5 (C-4); 163.0 (d, J = 248.8, Ar); 134.9 (d, J
2H); 0.93–1.05 (m, 1H). 13C NMR δ (D2O, 100 MHz,
ppm); 175.0 (C-4); 75.2 (C-2); 54.8 (2C, C-8); 54.0 (C-7);
37.8 (C-6); 37.0 (2C); 30.6 (C-5); 23.7; 23.1 (2C); 22.6
3
2
= 3.1, Ar); 129.2 (d, 2C, J = 8.4, Ar); 116.1 (d, 2C, J =
21.9, Ar); 62.7 (C-2); 49.1 (C-8); 45.6 (2C); 40.6 (C-6);