5
50
Helvetica Chimica Acta – Vol. 98 (2015)
n˜in cm . H- and 13C-NMR spectra: Bruker DRX-300 AVANCE spectrometers; at 300 and 75 MHz,
À1 1
resp.; in (D )DMSO; d in ppm rel. to Me Si as internal standard, J in Hz. MS: FINNIGAN-MAT 8430
6
4
mass spectrometer; at an ionization potential of 70 eV; in m/z. Elemental analyses: Heraeus CHN-O-
Rapid analyzer for C, H, and N.
Synthesis of Compounds 3 (exemplified for 3a). A mixture of isatin (1H-indole-2,3-dione; 1a;
1
mmol), ethyl cyanoacetate (NCCH COOEt; 1 mmol), and 1,2,3,4,5,6-hexahydro-2-(nitromethylide-
2
ne)pyrimidine (2a; 1 mmol), in the presence of NaCl (30 mol-%) in H O (15 ml) was stirred at reflux for
2
3
h. After completion of the reaction (TLC), the mixture was filtered and purified using flash
chromatography (FC) to afford the pure product 3a in good yield, besides spiro-oxindole 4a.
Synthesis of Compounds 4 (exemplified for 4b). A mixture of N-methylisatin (1b; 1 mmol),
NCCH COOEt (1 mmol), and 2a (1 mmol), in the presence of piperidine (one drop) in H O (15 ml) was
2
2
stirred at reflux for 3 h. After completion of the reaction (TLC), the mixture was filtered, and the
precipitate was washed with EtOH (4 ml) to afford the pure product 4b.
(
3S)-1,1’,2,2’,3’,4’,6’,7’-Octahydro-9’-nitro-2,6’-dioxospiro[3H-indole-3,8’-[8H]pyrido[1,2-a]pyrimi-
dine]-7’-carbonitrile (3a). Yield: 0.162 g (48%). Cream-colored powder. M.p. 269 – 2718. IR: 3425 and
1
3
2
6
1
192 (2 NH), 1726 (NCO and NHCO), 1618 (C¼C), 1494 and 1378 (NO ). H-NMR: 1.97 – 2.06 (m,
2
3
H); 3.42 – 3.54 (m, 2 H); 3.76 – 3.84 (m, 1 H); 3.94 – 4.02 (m, 1 H); 5.11 (s, 1 H); 6.88 (d, J ¼ 7.8, 1 H),
3
3
3
13
.94 (t, J ¼ 7.6, 1 H), 7.12 (d, J ¼ 7.4, 1 H ), 7.27 (t, J ¼ 7.7, 1 H); 10.89 (s, 1 H); 11.41 (s, 1 H). C-NMR:
8.5; 40.7; 43.6; 50.5; 50.6; 106.4; 109.8; 112.6; 121.9; 123.2; 125.6; 129.8; 142.7; 151.5; 161.0; 174.7. EI-MS:
þ
3
39 (5, M ), 293 (40), 250 (35), 127 (67), 114 (45), 44 (96), 30 (100). Anal. calc. for C H N O (339.31):
1
6
13
5
4
C 56.64, H 3.86, N 20.64; found: C 56.59, H 3.80, N 20.68.
(
3S)-1,1’,2,2’,3’,4’,6’,7’-Octahydro-1-methyl-9’-nitro-2,6’-dioxospiro[3H-indole-3,8’-[8H]pyrido[1,2-
a]pyrimidine]-7’-carbonitrile (3b). Yield: 0.149 g (45%). Cream-colored powder. M.p. 264 – 2658. IR:
1
3
411, 3061 (2 NH), 1708 (NCO and MeNCO), 1624 (C¼C), 1482 and 1347 (NO ). H-NMR: 1.97 – 2.05
2
(
m, 2 H); 3.20 (s, 3 H); 3.47 – 3.53 (m, 2 H); 3.74 – 3.82 (m, 1 H); 3.93 – 3.98 (m, 1 H); 5.18 (s, 1 H); 7.03 (t,
3
3
3
3
13
J ¼ 7.2, 1 H); 7.12 (d, J ¼ 7.3, 1 H); 7.19 (d, J ¼ 6.7, 1 H); 7.39 (t, J ¼ 6.9, 1 H); 11.41 (s, 1 H). C-NMR:
1
8.5; 26.7; 40.8, 43.5; 50.1; 50.3; 106.2; 108.9; 112.5; 122.7; 122.9; 124.9; 130.1; 144.1; 151.5; 160.9; 173.3.
þ
EI-MS: 353 (21, M ), 307 (34), 223 (47), 176 (48), 147 (88), 118 (100), 104 (51). Anal. calc. for
C H N O (353.33): C 57.79, H 4.28, N 19.82; found: C 57.74, H 4.35, N 19.88.
17
15
5
4
(
3S)-1,1’,2,2’,3’,4’,6’,7’-Octahydro-3’,3’-dimethyl-9’-nitro-2,6’-dioxospiro[3H-indole-3,8’-[8H]pyri-
do[1,2-a]pyrimidine]-7’-carbonitrile (3c). Yield: 0.176 g (48%). Orange powder. M.p. 254 – 2558. IR:
1
3
6
1
4
413, 3314, (2 NH), 1724 (NCO and NHCO), 1630 (C¼C), 1474 and 1345 (NO ). H-NMR: 1.06 (s,
2
2
3
3
H); 3.31 (s, 2 H); 3.68 (q, AB system, J ¼ 12.1, 2 H); 5.42 (s, 1 H); 6.91 (d, J ¼ 7.7, 1 H); 6.97 (t, J ¼ 7.7,
3
3
13
H); 7.00 (d, J ¼ 6.8, 1 H); 7.29 (t, J ¼ 6.8, 1 H); 10.89 (s, 1 H); 11.34 (s, 1 H). C-NMR: 23.0; 23.7, 28.9;
3.5; 50.3; 51.1; 51.5; 106.4; 109.9; 112.7; 122.0; 122.7; 125.7; 129.9; 142.7; 150.5; 161.3; 174.5. EI-MS: 367
þ
(
5, M ), 311 (15), 242 (44), 197 (41), 170 (100), 142 (80), 114 (66). Anal. calc. for C H N O (367.36): C
1
8
17
5
4
5
8.85, H 4.66, N 19.06; found: C 58.91, H 4.60, N 19.18.
3S)-1,1’,2,2’,3’,4’,6’,7’-Octahydro-1,3’,3’-trimethyl-9’-nitro-2,6’-dioxospiro[3H-indole-3,8’-[8H]pyri-
(
do[1,2-a]pyrimidine]-7’-carbonitrile (3d). Yield: 0.175 g (46%). Yellow powder. M.p. 264 – 2668. IR:
1
3
6
7
420, 3061 (2 NH), 1709 (NCO and MeNCO), 1623 (C¼C), 1484 and 1347 (NO ). H-NMR: 1.06 (s,
2
2
3
H); 3.21 (s, 3 H); 3.33 (s, 2 H); 3.68 (q, AB system, J ¼ 12.6, 2 H); 5.51 (s, 1 H); 7.04 (t, J ¼ 6.9, 1 H);
3
3
3
13
.1 (d, J ¼ 7.8, 1 H); 7.13 (d, J ¼ 7.8, 1 H); 7.40 (t, J ¼ 7.1, 1 H); 11.34 (s, 1 H). C-NMR: 23.0; 23.8; 26.7;
2
8.9; 43.4; 50.2; 50.4; 50.5; 106.3; 108.9, 112.6; 122.5; 122.8; 124.9; 130.2; 144.1; 150.6; 161.2; 173.1. EI-
þ
MS: 381 (39, M ), 335 (100), 320 (21), 224 (40), 209 (30), 155 (38), 41 (37). Anal. calc. for C H N O
1
9
19
5
4
(
381.39): C 59.84, H 5.02, N 18.36; found: C 59.76, H 4.98, N 18.41.
3S)-5-Bromo-1,1’,2,2’,3’,4’,6’,7’-octahydro-1-methyl-9’-nitro-2,6’-dioxospiro[3H-indole-3,8’-
(
[
8H]pyrido[1,2-a]pyrimidine]-7’-carbonitrile (3e). Yield: 0.156 g (43%). White powder. M.p. 2808
(
dec.). IR: 3396 and 3153 (2 NH), 1712 (NCO and MeNCO), 1689 (C¼C), 1480 and 1331 (NO ).
2
1
H-NMR: 1.95 – 2.12 (m, 2 H); 3.20 (s, 3 H); 3.63 – 3.67 (m, 2 H); 3.79 – 3.82 (m, 1 H); 3.98 – 4.02 (m,
1
1
2
2
13
H); 5.22 (s, 1 H); 7.11 (d, J ¼ 8.37, 1 H); 7.49 (s, 1 H); 7.59 (d, J ¼ 8.23, 1 H); 11.04 (s, 1 H). C-NMR:
8.3; 26.8; 45.4; 50.1; 54.3; 55.1; 106.1; 110.8; 114.5; 116.3; 122.1; 126.1; 132.8; 143.6; 151.4; 160.7; 175.6.
EI-MS: 418 (5), 399 (19), 334 (59), 264 (45), 176 (37), 155 (88), 110 (100). Anal. calc. for C H BrN O
4
1
7
14
5
(
432.23): C 47.24, H 3.26, N 16.20; found: C 47.31, H 3.21, N 16.16.