Med Chem Res
(C=O), 877.3 (C–Cl). ESI MS (m/z) 437.8, Calcd. mass:
437.9. HRMS (ESI-TOF)m/z:[M?H]? Calcd. for C18H17
ClFN5O3SH 438.0803; Found 438.0807.
NMR(400 MHz, DMSO-d6): d 1.86 (s, 1H), 2.03 (d,
J = 3.20 Hz, 1H), 2.21 (s, 3H), 2.65 (d, J = 12.80 Hz,
1H), 2.83 (t, J = 21.60 Hz, 2H), 3.15 (d, J = 4.40 Hz,
2H), 3.46 (s, 1H), 3.95 (d, J = 13.20 Hz, 1H), 6.66 (t,
J = 14.00 Hz, 1H), 6.89-6.96 (m, 2H), 7.03 (t,
J = 15.60 Hz, 1H), 11.28 (s, 1H), 11.45 (s, 1H), 13C-NMR
(250 MHz, DMSO-d6): d (ppm) 32.20, 45.50, 46.49, 50.00,
53.13, 54.88, 112.87, 117.82, 121.58, 126.41, 128.33,
150.05, 168.88, 171.48. IR (KBr, cm-1) 3433.6 (N–H)
3092.3 (C–H, aromatic), 2923.6 (C–H, alkane), 1726.9
(C=O general carbonyl). HRMS (ESI-TOF) m/z:[M?H]?
Calcd. for C16H18N4O3H 315.1457; Found 315.1455.
8-Chloro-11-fluoro-3-phenyl-20-thioxo-1,2,20,3,30,4,4a,6-oc-
tahydro-10H-spiro[isoxazolo[4,5-g]pyrazino[1,2-a]quino-
line-5,50-pyrimidine]-40,60-dione (8j) Dark brown solid
1
(0.11 g, 90.9 %); mp: 292–295 °C. H-NMR (400 MHz,
DMSO-d6): d (ppm) 2.92 (t, J = 20.80 Hz, 1H), 3.26 (s,
2H), 3.44–3.57 (m, 3H), 3.69 (dd, J = 12.0, 19.6 Hz, 2H),
4.08 (d, J = 7.60 Hz, 1H), 6.80 (t, J = 14.40 Hz, 1H),
7.15–7.23 (m, 4H), 7.35 (s, 1H), 12.38 (s, 1H), 12.67 (s,
1H).13C-NMR (250 MHz, DMSO-d6): d (ppm) 36.90,
48.43, 49.29, 49.41, 51.70, 59.46, 114.28, 115.52, 124.17,
124.65, 125.25, 128.14, 128.92, 132.68, 148.58, 150.30,
3-Ethyl-1,2,3,4,4a,6-hexahydro-10H-spiro[pyrazino[1,2-a]
quinoline-5,50-pyrimidine]-20,40,60(30H)-trione (11d) Pale
pink solid (0.13 g, 88.6 %); mp: 224–226 °C.
1H-NMR(400 MHz, DMSO-d6): d 1.02 (t, J = 19.60 Hz,
3H), 1.27 (q, J = 25.20 Hz, 4H), 2.03 (d, J = 3.20 Hz,
1H), 2.33 (s, 2H), 2.69 (q, J = 18.80 Hz, 1H), 2.84 (q,
J = 38.80 Hz, 2H), 3.15 (dd, J = 16.8, 29.2 Hz, 2H), 3.94
(d, J = 11.60 Hz, 1H), 6.67 (t, J = 14.40 Hz, 1H), 6.93
(dd, J = 8.0, 20.6 Hz, 2H), 7.04 (t, J = 23.60 Hz, 1H),
11.27 (s, 1H), 11.47 (s, 1H).13C-NMR (250 MHz, DMSO-
d6): d (ppm) 11.65, 32.51, 46.61, 49.96, 50.93, 51.47,
52.90, 112.96, 117.82, 121.62, 126.36, 128.31, 150.06,
168.99. IR (KBr, cm-1) 3419.2 (N–H) 3091.3 (C–H, aro-
matic), 2978.5 (C–H, alkane), 1723.1 (C=O general car-
bonyl). HRMS (ESI-TOF) m/z:[M?H]? Calcd. for
C17H20N4O3H 329.1614; Found 329.1614.
152.09, 152.23, 167.62, 168.63, 178.68. IR (KBr, cm-1
)
3196.4 (N–H) 2924.1 (C–H, aromatic), 2855.1 (C–H,
alkane), 1695.1 (C=O), 746.7 (C–Cl). ESI MS (m/z) 485.8,
Calcd. mass: 485.9.HRMS (ESI-TOF)m/z:[M?Na]?
Calcd. for C22H17ClFN5O3SNa 508.0622; Found 508.0622.
2,4,4a,6-Tetrahydro-1H,10H-spiro[[1,4]oxazino[4,3-a]quino-
line-5,50-pyrimidine]-20,40,60(30H)-trione
(11a) Cream
solid (0.15 g, 95.5 %); mp: 167–169 °C. 1H-NMR
(400 MHz, DMSO-d6): d 2.84–2.91 (m, 1H), 3.10-3.30 (m,
2H), 3.38 (d, J = 2.40 Hz, 2H), 3.46–3.53 (m, 1H), 3.70
(dd, J = 2.4, 10.6 Hz, 1H), 3.85 (t, J = 21.20 Hz, 2H),
6.68 (t, J = 14.00 Hz, 1H), 6.93 (dd, J = 8.4, 26.6 Hz,
2H), 7.06 (t, J = 12.00 Hz, 1H), 11.29 (s, 1H), 11.50 (s,
1H). 13C-NMR (250 MHz, DMSO-d6): d (ppm) 33.19,
46.70, 48.89, 58.64, 65.75, 66.02, 112.67, 118.04, 121.39,
126.47, 128.36, 144.28, 149.92, 168.66, 171.28. IR (KBr,
cm-1) 3323.7 (N–H) 3092.3 (C–H, aromatic), 2987.2 (C–
H, alkane), 1752.0 (C=O general carbonyl). HRMS (ESI-
TOF) m/z:[M?Na]? Calcd. for C15H15N3O4Na 324.0960;
Found 324.0960.
3-Phenyl-1,2,3,4,4a,6-hexahydro-10H-spiro[pyrazino[1,2-a]
quinoline-5,50-pyrimidine]-20,40,60(30H)-trione (11e) Buff
solid (0.15 g, 84.1 %); mp: 258–261 °C. 1H-NMR
(400 MHz, DMSO-d6): d 3.07 (t, J = 20.80 Hz, 2H), 3.17
(d, J = 16.80 Hz, 2H), 3.44 (d, J = 15.20 Hz, 2H),
3.60–3.67 (m, 2H), 4.08 (d, J = 12.40 Hz, 1H), 6.67 (t,
J = 14.40 Hz, 1H), 6.82 (t, J = 14.40 Hz, 1H), 6.89 (d,
J = 7.60 Hz, 2H), 6.97 (t, J = 14.00 Hz, 2H), 7.06 (t,
J = 15.60 Hz, 1H), 7.24 (t, J = 16.00 Hz, 2H), 11.30 (s,
1H), 11.49 (s, 1H), 13C-NMR (250 MHz, DMSO-d6): d
(ppm) 33.01, 46.55, 47.49, 48.69, 50.09, 58.42, 112.99,
115.66, 117.74, 119.52, 121.18, 126.64, 128.44, 129.09,
143.92, 150.05, 150.31, 167.70, 168.83, 171.52. IR (KBr,
cm-1) 3317.0 (N–H) 3093.3 (C–H, aromatic), 2955.4 (C–
H, alkane), 1683.6 (C=O general carbonyl). HRMS (ESI-
TOF) m/z:[M?Na]? Calcd. for C21H20N4O3Na 399.1433;
Found 399.1437.
2,4,4a,6-Tetrahydro-1H,10H-spiro[[1,4]thiazino[4,3-a]quino-
line-5,50-pyrimidine]-20,40,60(30H)-trione
(11b) Orange
solid (0.11 g, 71.8 %); mp: 180–182 °C. 1H-NMR
(400 MHz, DMSO-d6): d 2.57 (d, J = 13.20 Hz, 2H), 2.82
(t, J = 17.60 Hz, 2H), 3.29–3.46 (m, 3H), 4.00 (d,
J = 10.40 Hz, 1H), 4.39 (d, J = 14.80 Hz, 1H), 6.68 (t,
J = 14.40 Hz, 1H), 6.82 (d, J = 8.40 Hz, 1H), 7.02–7.12
(m, 2H), 11.12 (s, 1H), 11.32 (s, 1H). 13C-NMR (250 MHz,
DMSO-d6): d (ppm) 25.42, 25.57, 50.33, 53.64, 61.94,
62.45, 113.28, 117.57, 122.21, 126.53, 128.91, 141.04,
167.66, 169.59, 169.99. IR (KBr, cm-1) 3443.3 (N–H)
3090.4 (C–H, aromatic), 2924.5 (C–H, alkane), 1726.0
(C=O general carbonyl). HRMS (ESI-TOF) m/z:[M?Na]?
Calcd. for C15H15N3O3SNa 340.0732; Found 340.0730.
20-Thioxo-2,20,30,4,4a,6-hexahydro-1H,10H-spiro[[1,4]oxazino
[4,3-a]quinoline-5,50-pyrimidine]-40,60-dione (11f) Green-
1
ish yellow solid (0.15 g, 95.1 %); mp: 122–124 °C. H-
NMR(400 MHz, DMSO-d6): d 2.87-2.93 (m, 1H), 3.17 (t,
J = 32.40 Hz, 2H), 3.29 (t, J = 21.20 Hz, 2H), 3.49 (q,
J = 20.40 Hz, 1H), 3.69 (d, J = 8.80 Hz, 1H), 3.84 (d,
3-Methyl-1,2,3,4,4a,6-hexahydro-10H-spiro[pyrazino[1,2-a]
quinoline-5,50-pyrimidine]-20,40,60(30H)-trione
(11c)
Brown solid (0.14 g, 92.1 %); mp: 208–211 °C. 1H-
123