RCHH HARM
A P
Arch. Pharm. Chem. Life Sci. 2017, 350, e1700052
S. Sert-Ozgur et al.
Archiv der Pharmazie
160.70 (C-2). IR vmax cmꢀ1: 3029 (C-H aromatic), 2850 (C-H
(2H; s; -S-CH2), 5.15 (2H; s; -N-CH2), 7.19–7.30 (10H; m; ArH).
13C-NMR (DMSO, d6): d 32.75 (-CH2-CH2-Ph), 33.86 (Ph-CH2-),
50.74 (-N-CH2-CH2-), 54.96 (C-5), 67.03 (C-7), 125.98 (Ph C-4),
126.11 (Ph C-40), 128.17 (Ph C-20, C-60), 128.54 (Ph C-3, C-5, C-30,
C-50), 128.64 (Ph C-2, C-6), 138.07 (Ph C-1), 139.20 (Ph C-10),
146.60 (C-3a), 160.33 (C-2). IR vmax cmꢀ1: 3027 (C-H aromatic),
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aliphatic), 1602 (C N), 1438 (C C), 1134 (C-N), 634 (C-S). ESI-MS
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m/z(%):345(MþþNa, 4.73%), 323 (MþþH, 7.10%), 232, 218, 200
(100%), 186, 168, 146, 105. Anal. calcd. for C18H18N4S:C,67.05;H,
5.63; N, 17.38; S, 9.94. Found: C, 66.74; H, 5.74; N, 17.20; S, 9.90.
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(S)-(ꢀ)-2-Phenyl-6-(1-phenethyl)-6,7-dihydro-5H-1,2,4-
triazolo[3,2-b]-1,3,5-thiadiazine (1d)
2927 (C-H aliphatic), 1604 (C N), 1440 (C C), 1120 (C-N), 696
–
–
(C-S). ESI-MS m/z (%): 359 (MþþNa, 49.70%), 337 (MþþH,
31.95%), 232 (100%), 200, 146, 134, 105, 71, 60. Anal. calcd.
for C19H20N4S: C, 67.83; H, 5.99; N, 16.65; S, 9.53. Found: C,
67.68; H, 6.33; N, 16.48; S, 9.34.
Yield 57%, mp 84–86°C. [a]D 25° ¼ ꢀ56.7 (0.6 mg/mL in CHCl3).
1H NMR (CDCI3): d 1.48 (3H; d; -CH-CH3), 4.07 (1H; q; -CH-CH3),
4.59(1H;d;J:12.4 Hz;-S-CH2),4.86(1H;d;J:12.4 Hz;-S-CH2),5.11
(1H; d; J: 13.6 Hz; -N-CH2), 5.34 (1H; d; J: 13.6 Hz; -N-CH2),
7.26–8.07 (10H; m; ArH). 13C-NMR (CDCl3): d 19.20 (CH3-), 58.75
(-N-CH-Ph), 58.78 (C-5), 65.09 (C-7), 127.43 (Ph C-2, C-6), 127.55
(C-40), 128.54 (Ph C-20, C-30, C-50, C-60), 128.79 (Ph C-4), 129.30 (Ph
C-3, C-5), 130.79 (Ph C-1), 136.6 (Ph C-10), 151.55 (C-3a), 160.50
(C-2). IR vmax cmꢀ1: 2984 (C-H aromatic), 2848 (C-H aliphatic),
(S)-6-Butyl-2-[1-(6-methoxy-2-naphthyl)ethyl]-6,7-
dihydro-5H-1,2,4-triazolo[3,2-b]-1,3,5-thiadiazine (3a)
Yield 50%, mp 88–90°C. [a]D 25° ¼ þ35.0 (0.6 mg/mL in CHCl3).
1H NMR (CDCI3): d 0.93 (3H; t; -CH2-CH3), 1.36 (2H; m; -CH2-
CH3), 1.53 (2H; m; CH2-CH2-CH2-), 1.75 (3H; d; -CH-CH3), 2.76
(2H; t; -N-CH2-CH2-), 3.89 (3H; s; -OCH3), 4.34 (1H; q; -CH-CH3),
4.64 (2H; s; -S-CH2), 5.05 (2H; s; -N-CH2), 7.09–7.72 (6H; m; ArH).
13C-NMR (CDCI3): d 14.07 (-CH2-CH3), 20.30 (-CH2-CH3, -CH-
CH3), 29.62 (-CH2-CH2-CH2-), 38.86 (-CH-CH3), 50.25 (-N-CH2-
CH2-), 55.78 (C-5), 55.90 (OCH3), 67.90 (C-7), 115.83–132.80
(naphthyl C-1, C-3, C-4, C-4a, C-5, C-7, C-8, C-8a), 133.79
(naphthyl C-2), 151.60 (C-3a), 156.29 (naphthyl C-6), 161.00 (C-
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1603 (C N), 1438 (C C), 1132 (C-N), 608 (C-S). ESI-MS m/z (%):
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345 (MþþNa, 4.73%), 323 (MþþH, 15.38%), 232, 219, 200, 190,
156, 148, 105 (100%). Anal. calcd. for C18H18N4S: C, 67.05; H,
5.63; N, 17.38; S, 9.94. Found: C, 66.81; H, 5.53; N, 16.88; S, 9.88.
2-Benzyl-6-butyl-6,7-dihydro-5H-1,2,4-triazolo[3,2-b]-
1,3,5-thiadiazine (2a)
Yield 85%, mp 75–77°C. 1H NMR (CDCI3): d 0.85 (3H; t; -CH2-
CH3), 1.27 (2H; m; -CH2-CH3), 1.46 (2H; m; CH2-CH2-CH2-), 2.61
(2H; t; -N-CH2-CH2-), 3.86 (2H; s; Ar-CH2-), 4.83 (2H; s; -S-CH2),
5.09 (2H; s; -N-CH2), 7.17–7.27 (5H; m; ArH). 13C-NMR (CDCI3): d
14.07 (-CH2-CH3), 20.30 (-CH2-CH3), 29.62 (-CH2-CH2-CH2-),
33.86 (Ph-CH2-), 50.25 (-N-CH2-CH2-), 55.78 (C-5), 67.90 (C-7),
125.83 (Ph C-4), 128.79 (Ph C-3, C-5), 129.43 (Ph C-2, C-6),
136.79 (Ph C-1), 150.89 (C-3a), 160.70 (C-2). IR vmax cmꢀ1: 2930
2). IR vmax cmꢀ1: 2934 (C-H aliphatic), 1606 (C N), 1440 (C C),
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–
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1264 (C-O), 1031 (C-N), 631 (C-S). ESI-MS m/z (%): 405 (MþþNa,
28.40%), 383 (MþþH, 26.04%), 184, 170, 152 (100%), 108, 100,
86, 57. Anal. calcd. for C21H26N4OS: C, 65.94; H, 6.85; N, 14.65;
S, 8.38. Found: C, 65.73; H, 6.49; N, 14.28; S, 7.89.
(S)-6-Benzyl-2-[1-(6-methoxy-2-naphthyl)ethyl]-6,7-
dihydro-5H-1,2,4-triazolo[3,2-b]-1,3,5-thiadiazine (3b)
Yield 60%, mp 82–84°C. [a]D 25° ¼ þ47.0 (0.6 mg/mL in CHCl3).
1H NMR (CDCI3): d 1.77 (3H; d; -CH-CH3), 3.90 (3H; s; -OCH3),
3.94 (2H; s; -CH2-Ar), 4.37 (1H; q; -CH-CH3), 4.56 (2H; s; -S-CH2),
5.12 (2H; s; -N-CH2), 7.10–7.74 (11H; m; ArH). 13C-NMR (CDCI3):
d 20.30 (-CH-CH3), 38.86 (-CH-CH3), 55.90 (OCH3), 56.25 (-N-
CH2-Ph), 59.78 (C-5), 67.90 (C-7), 115.83–132.80 (naphthyl C-1,
C-3, C-4, C-4a, C-5, C-7, C-8, C-8a, and Ph C-2, C-3, C-4, C-5, C-6),
133.79 (naphthyl C-2), 135.60 (Ph C-1), 151.60 (C-3a), 156.29
(naphthyl C-6), 161.00 (C-2). IR vmax cmꢀ1: 2975 (C-H aliphatic),
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(C-H aliphatic), 1568 (C N), 1496 (C C), 1176 (C-N), 695 (C-S).
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ESI-MS m/z (%): 311 (MþþNa, 31.25%), 289 (MþþH, 90.63%),
258, 252, 236, 216, 184 (100%), 170, 152. Anal. calcd. for
C
15H20N4S: C, 62.47; H, 6.99; N, 19.43; S, 11.12. Found: C, 62.16;
H, 7.09; N, 19.17; S, 11.22.
2,6-Dibenzyl-6,7-dihydro-5H-1,2,4-triazolo[3,2-b]-1,3,5-
thiadiazine (2b)
Yield 82%, mp 130–131°C. 1H NMR (CDCI3): d 3.93 (2H; s; -N-
CH2-Ar), 4.04 (2H; s; Ar-CH2-), 4.58 (2H; s; -S-CH2), 5.11 (2H; s;
-N-CH2), 7.22–7.38 (10H; m; ArH). 13C-NMR (CDCI3): d 34.86 (Ph-
CH2-), 56.25 (-N-CH2-Ph), 59.78 (C-5), 66.89 (C-7), 125.79 (Ph C-
4), 127.43 (Ph C-40), 128.95 (Ph C-2, C-3, C-5, C-6, C-20, C-30, C-50,
C-60), 135.79 (Ph C-1, C-10), 151.49 (C-3a), 160.40 (C-2). IR vmax
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1606 (C N), 1455 (C C), 1264 (C-O), 1030 (C-N), 642 (C-S). ESI-
MS m/z (%): 439 (MþþNa, 24.26%), 417 (MþþH, 33.73%), 218,
204, 186, 164, 120, 102, 91 (100%). Anal. calcd. for
C
24H24N4OS: C, 69.20; H, 5.81; N, 13.45; S, 7.70. Found: C,
68.90; H, 6.10; N, 13.32; S, 7.27.
cmꢀ1: 3031 (C-H aromatic), 2858 (C-H aliphatic), 1605 (C N),
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1494 (C C), 1152 (C-N), 698 (C-S). ESI-MS m/z (%): 345
(S)-6-Phenethyl-2-[1-(6-methoxy-2-naphthyl)ethyl]-6,7-
dihydro-5H-1,2,4-triazolo[3,2-b]-1,3,5-thiadiazine (3c)
Yield 83%, mp 138–140°C. [a]D 25° ¼ þ43.0 (0.6 mg/mL in
CHCl3). 1H NMR (CDCI3): d 1.74 (3H; d; -CH-CH3), 2.86 (2H; t;
-CH2-Ar), 3.05 (2H; t; -N-CH2-CH2-), 3.90 (3H; s; -OCH3), 4.33
(1H; q; -CH-CH3), 4.62 (2H; s; -S-CH2), 5.06 (2H; s; -N-CH2), 7.08–
7.71 (11H; m; ArH). 13C-NMR (CDCI3): d 20.30 (-CH-CH3), 33.75
(-CH2-CH2-Ph), 38.86 (-CH-CH3), 50.74 (-N-CH2-CH2-), 55.95
(OCH3), 60.78 (C-5), 67.92 (C-7), 118.83–132.80 (naphthyl C-1,
–
(MþþNa, 100%), 323 (MþþH, 84.02%), 226, 218, 204, 186,
120, 91, 60. Anal. calcd. for C18H18N4S: C, 67.05; H, 5.63; N,
17.38; S, 9.94. Found: C, 67.29; H, 5.63; N, 17.21; S, 9.87.
2-Benzyl-6-phenethyl-6,7-dihydro-5H-1,2,4-triazolo[3,2-
b]-1,3,5-thiadiazine (2c)
Yield 81%, mp 78–80°C. H NMR (DMSO): d 2.84 (2H; t; -CH2-
CH2-Ar), 2.91 (2H; t; -N-CH2-CH2-), 3.89 (2H; s; Ar-CH2-), 4.90
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ß 2017 Deutsche Pharmazeutische Gesellschaft
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