Ç.B. Apaydın et al.
Bioorganic Chemistry 112 (2021) 104958
1
3
–
–
–
(C O), 1670 (NHC O). H NMR (DMSO‑d /500 MHz): 0.83 (3H, t, J
141 (70.46). Anal. calcd. for C16H22N2O3S (322.42) C: 59.60, H: 6.88, N:
8.69. Found C: 59.54, H: 6.84, N: 8.55.
–
6
= 7 Hz, sp-8-CH2CH2CH3), 1.11–1.20 (5H, m, sp-8-CH2CH2CH3, sp-7ax
-
H, sp-9ax-H and sp-8-H), 1.23–1.27 (2H, m, sp-8-CH2CH2CH3),
1.72–1.82 (6H, m, sp-6-H, sp-7eq-H and sp-9eq-H, sp-10-H), 3.29 (3H, s,
frn-2-CH3), 3.58 (2H, s, sp-2-H), 6.92 (1H, d, 3J = 2 Hz, frn-4-H), 7.57
(1H, d, 3J = 2 Hz, frn-5-H), 10.01 (1H, s, NH). Anal. calcd. for
4.2.10. N-(8-ethyl-2-methyl-3-oxo-1-thia-4-azaspiro[4.5]dec-4-yl)-2-
methylfuran-3-carboxyamide (3c)
ꢀ 1
Yield: 52%. mp: 160–162 ◦C; IR (KBr) ʋ (cm ): 3227 (N H), 1705
–
1
3
–
–
–
C
17H24N2O3S (336.44) C: 60.69, H: 7.19, N: 8.33. Found C: 60.89, H:
(C O), 1678 (NHC O). H NMR (CDCl /500 MHz): 0.78 (3H, t, J = 7
–
3
7.27, N: 8.52.
Hz, sp-8-CH2CH3), 0.93–1.03 (1H, m, sp-8-H), 1.03–1.28 (2H, m, sp-
3
7ax-H and sp-9ax-H), 1.15 (2H, q, J = 7 Hz, sp-8-CH2), 1.49 (3H, d,
4.2.6. N-(8-tert-butyl-3-oxo-1-thia-4-azaspiro[4.5]dec-4-yl)-2-
3J = 7 Hz, sp-2-CH3), 1.68–1.81 (4H, m, sp-6 eq-H, sp-10ax-H, sp-7 eq-H
and sp-9 eq-H), 1.83 (1H, d, 2J = 13 Hz, sp-10 eq-H), 1.90–1.96 (1H, m,
sp-6ax-H), 2.39 (3H, s, frn-2-CH3), 3.79 (1H, q, 3J = 7 Hz, SCH), 6.64
(1H, d, 3J = 2 Hz, frn-4-H), 7.07 (1H, d, 3J = 2 Hz, frn-5-H), 8.89 (1H, s,
NH). 13C NMR (APT) (CDCl3/125 MHz): 10.43 (sp-C8-CH2CH3), 12.54
(frn-C2-CH3), 18.91 (sp-C2-CH3), 28.10 (sp-C8-CH2), 28.05 and 28.56
(sp-C7 and sp-C9), 36.61 (sp-C2), 36.66 (sp-C8), 36.13 and 37.30 (sp-C6
and sp-C10), 71.60 (sp-C5), 107.54 (frn-C4), 111.62 (frn-C3), 139.02
(frn-C5), 158.07 (frn-C2), 162.05 (NHCO), 172.12 (sp-C3). ESI (-) MS m/
z (%): 335 ([Mꢀ H]ꢀ , 18.82), 291 (26.80),263 (48.48), 247 (1 0 0), 141
(43.28). Anal. calcd. for C17H24N2O3S. 0.5 H2O (345.45) C: 59.10, H:
7.29, N: 8.11. Found C: 59.68; H: 7.17; N: 8.23.
methylfuran-3-carboxamide (2e)
ꢀ 1
Yield: 68%. mp: 180–182 ◦C; IR (KBr) ʋ (cm ): 3236 (N H), 1701
–
1
–
–
–
–
(C O), 1670 (NHC O). H NMR (DMSO‑d /500 MHz): 0.81 (9H, s, sp-
8-C(CH3)3), 0.85–0.93 (1H, m, C8-H), 1.186–1.22 (2H, m, sp-7ax-H and
sp-9ax-H), 1.70–2.20 (6H, m, sp-6-H, sp-7eq-H and sp-9eq-H, sp-10-H),
3
3.30 (3H, s, frn-2-CH3), 3.58 (2H, s, sp-2-H), 6.92 (1H, d, J = 2 Hz,
frn-4-H), 7.57 (1H, d, 3J = 2 Hz, frn-5-H), 10.02 (1H, s, NH). Anal. calcd.
for C18H26N2O3S⋅H2O (368.47) C: 58.67, H: 7.66, N: 7.99. Found C:
58.50, H: 7.46, N: 7.86.
4.2.7. N-(3-oxo-8-phenyl-1-thia-4-azaspiro[4.5]dec-4-yl)-2-methylfuran-
3-carboxamide (2f)
ꢀ 1
Yield: 75%. mp: 224–226 ◦C; IR (KBr) ʋ (cm ): 3296 (N H), 1703
4.2.11. N-(2-methyl-3-oxo-8-propyl-1-thia-4-azaspiro[4.5]dec-4-yl)-2-
–
1
–
–
–
–
(C O), 1681 (NHC O). H NMR (DMSO‑d /400 MHz): 1.64–1.67 (2H,
methylfuran-3-carboxamide (3d)
m, sp-7ax-H and sp-9ax-H), 1.85–2.20 (6H6, m, sp-6-H, sp-7 eq-H, sp-9
eq-H and sp-10-H), 2.46–2.48 (1H, m, sp-8-H and DMSO‑d6), 3.31 (3H,
s, frn-2-CH3 and DMSO-H2O), 3.64 (2H, s, sp-2-H), 6.96 (1H, d, 3J = 2
Hz, frn-4-H), 7.14–7.32 (5H, m, phenyl H), 7.60 (1H, d, 3J = 2 Hz, frn-5-
H), 10.11 (1H, s, NH).
Yield: 40%. mp: 172–174 ◦C; IR (KBr) ʋ (cm ): 3234 (N H), 1704
ꢀ 1
–
1
–
–
–
(C O), 1675 (NHC O). H NMR (CDCl /500 MHz): 0.79 and 0.81 (3H,
–
3
3
tt, J = 7 Hz, sp-8-CH2CH2CH3), 1.10 (2H, m, sp-C8-CH2), 1.05–1.27
(3H, m, sp-7ax-H, sp-9-ax-H and sp-8-H), 1.20 (2H, m, sp-8-CH2CH2),
1.49 (3H, d, 3J = 7 Hz, sp-2-CH3), 1.66–1.73 (2H, m, sp-7 eq-H and sp-9
eq-H), 1.73–1.81 (2H, m, sp-6 eq-H and sp-10ax-H), 1.83 (1H, d, 2J = 13
Hz sp-10 eq-H), 1.88–1.97 (1H, m, sp-6ax-H), 2.41 (3H, s, frn-2-CH3),
3.79 (1H, q, 3J = 7 Hz, SCH), 6.60 (1H, d, 3J = 2 Hz, frn-4-H), 7.10 (1H,
4.2.8. N-(2-methyl-3-oxo-1-thia-4-azaspiro[4.5]dec-4-yl)-2-methylfuran-
3-carboxamide (3a)
ꢀ 1
3
Yield: 45%. mp: 173–175 ◦C; IR (KBr) ʋ (cm ): 3294 (N H), 1708
d, J = 2 Hz, frn-5-H), 8.56 (1H, s, NH). 13C NMR (APT) (CDCl3/125
–
1
–
–
–
–
(C O), 1660 (NHC O). H NMR (CDCl /500 MHz): 0.93–1.04 (1H, m,
MHz): 13.78 (frn-C2-CH3), 14.42 (sp-C8-CH2CH2CH3), 20.14 (sp-C2-
CH3), 20.20 (sp-C8-CH2CH2), 29.66 and 30.16 (sp-C7 and sp-C9), 35.82
(sp-C8), 37.84 (sp-C2), 37.39 and 38.55 (sp-C6 and sp-C10), 38.92 (sp-
C8-CH2), 72.81 (sp-C5), 108.76 (frn-C4), 112.84 (frn-C3), 140.27 (frn-
C5), 159.32 (frn-C2), 163.30 (NHCO), 173.33 (sp-C3). ESI (-) MS m/z
(%): 349 ([Mꢀ H]ꢀ , 18.32), 305 (14.27), 277 (28.17), 261 (1 0 0), 141
(35.56). Anal. calcd. for C18H26N2O3S. 0.25 H2O (354.97) C: 60.90, H:
7.52, N: 7.89. Found C: 60,81, H: 7.40, N: 7.52.
3
sp-8ax-H), 1.36–1.51 (2H, m, sp-7ax-H and sp-9ax-H), 1.49 (3H, d, 3J = 7
Hz, sp-2-CH3), 1.51–1.58 (1H, m, sp-8eq-H), 1.65–1.72 (2H, m, sp-7eq-H
and sp-9eq-H), 1.73 (1H, d, 3J = 13 Hz, sp-10eq-H), 1.74 (1H, d, 2J = 13
Hz, sp-6eq-H), 1.82 (1H, d, 2J = 13 Hz, sp-10eq-H), 1.85–2.00 (1H, m, sp-
6
ax-H), 2.39 (3H, s, frn-2-CH3), 3.79 (1H, q, 3J = 7 Hz, SCH), 6.65 (1H, d,
3J = 2 Hz, frn-4-H), 7.07 (1H, d, 3J = 2 Hz, frn-5-H), 8.85 (1H, s, NH).
13C NMR (DEPT) (CDCl3/125 MHz): 13.79 (frn-C2-CH3), 20.12 (sp-C2-
CH3), 23.25 and 23.73 (sp-C7 and sp-C9), 24.59 (sp-C8), 37.82 (sp-C2),
37.63 and 38.80 (sp-C6 and sp-C10), 108.75 (frn-C4), 140.28 (frn-C5).
ESI (-) MS m/z (%): 307 ([Mꢀ H]ꢀ , 38.8), 263 (18.82), 235 (46.94), 219
(1 0 0), 141 (75.00). Anal. calcd. for C15H20N2O3S (308.39) C: 58.42, H:
6.54, N: 9.08. Found C: 58.52, H: 6.19, N: 9.02.
4.2.12. N-(8-tert-buthyl-2-methyl-3-oxo-1-thia-4-azaspiro[4.5]dec-4-yl)-
2-methylfuran-3-carboxamide (3e)
ꢀ 1
Yield: 56%. mp: 226–228 ◦C; IR (KBr) ʋ (cm ): 3319 (N H), 1715
–
1
–
–
–
(C O), 1671 (NHC O). H NMR (CDCl /500 MHz): 0.77 (9H, s, sp-8-C
–
(CH3)3), 0.85 (1H, tt, 3J = 12 Hz, 3J = 33Hz, sp-8-H), 1.15–1.32 (2H, m,
sp-7ax-H and sp-9ax-H), 1.50 (3H, d, 3J = 7 Hz, sty-2-CH3), 1.69–1.77
(2H, m, sp-7 eq-H and sp-9 eq-H), 1.77–1.85 (2H, m, sp-6 eq-H and sp-
10ax-H), 1.85–1.98 (2H, m, sp-6ax-H and sp-10 eq-H), 2.42 (3H, s, frn-2-
CH3), 3.79 (1H, q, 3J = 7 Hz, SCH), 6.60 (1H, d, 3J = 2 Hz, frn-4-H), 7.10
(1H, d, 3J = 2 Hz, frn-5-H), 8.55 (1H, s, NH). 13C NMR (HMBC) (CDCl3/
125 MHz): 12.58 (frn-C2-CH3), 19.00 (sp-C2-CH3), 22.92 and 23.37 (sp-
C7 and sp-C9), 26.45 (sp-C8-C(CH3)3), 31.23 (sp-C8-C), 36.61 (sp-C2),
36.56 and 37.68 (sp-C6 and sp-C10), 45.35 (sp-C8), 71.37 (sp-C5),
107.47 (frn-C4), 111.63 (frn-C3), 139.13 (frn-C5), 158.12 (frn-C2),
162.12 (NHCO), 171.98 (sp-C3). 13C NMR (DEPT) (CDCl3/125 MHz):
12.57 (frn-C2-CH3), 19.00 (sp-C2-CH3), 22.91 and 23.36 (sp-C7 and sp-
C9), 26.44 (sp-C8-C(CH3)3), 36.60 (sp-C2), 36.54 and 37.67 (sp-C6 and
sp-C10), 45.34 (sp-C8), 107.45 (frn-C4), 139.12 (frn-C5). ESI (-) MS m/z
(%): 363 ([Mꢀ H]ꢀ , 8.52), 319 (11.26), 291 (48.27), 275 (1 0 0), 141
4.2.9. N-(2,8-dimethyl-3-oxo-1-thia-4-azaspiro[4.5]dec-4-yl)-2-
methylfuran-3-carboxamide (3b)
ꢀ 1
Yield: 17%. mp: 168–169 ◦C; IR (KBr) ʋ (cm ): 3234 (N H), 1708
–
1
3
–
–
–
–
(C O), 1673 (NHC O). H NMR (CDCl /500 MHz): 0.82 (3H, d, J = 6
3
Hz, sp-8-CH3), 1.08–1.26 (3H, m, sp-7ax-H, sp-9ax-H and sp-8-H), 1.49
(3H, d, 3J = 7 Hz, sp-2-CH3), 1.60–1.68 (2H, m, sp-7 eq-H and sp-9 eq-
H), 1.73 (1H, d, 2J = 13 Hz, sp-6 eq-H), 1.76–1.85 (2H, m, sp-10 eq-H
and sp-10ax-H), 1.92–1.96 (1H, m, sp-6ax-H), 2.39 (3H, s, frn-2-CH3),
3.79 (1H, q, 3J = 7 Hz, SCH), 6.64 (1H, d, 3J = 2 Hz, frn-4-H), 7.08 (1H,
d, 3J = 2 Hz, frn-5-H), 8.87 (1H, s, NH). 13C NMR (DEPT) (CDCl3/125
MHz): 12.55 (frn-C2-CH3), 18.88 (sp-C2-CH3), 20.79 (sp-C8-CH3), 30.02
(sp-C8), 30.44 and 30.95 (sp-C7 and sp-C9), 36.60 (sp-C2), 36.12 and
37.30 (sp-C6 and sp-C10), 107.52 (frn-C4), 139.03 (frn-C5). ESI (-) MS
m/z (%): 321 ([Mꢀ H]ꢀ , 14.90), 277 (12.15), 249 (40.83); 233 (1 0 0),
5