Efficient and convenient Polyethylene Glycol (PEG)-mediated synthesis of spiro-oxindoles

Article abstract of DOI:10.1002/hlca.200900273

Polyethylene glycol (PEG) has been reported as an efficient and convenient medium for the three-component synthesis for spiro-oxindole.

Full text of DOI:10.1002/hlca.200900273

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Helvetica Chimica Acta – Vol. 93 (2010)
Efficient and Convenient Polyethylene Glycol (PEG)-Mediated Synthesis of
Spiro-oxindoles
by Harshadas Mitaram Meshram*, Dachepally Aravind Kumar, Busam Ramalinga Vara Prasad, and
Palakuri Ramesh Goud
Discovery Laboratory, Organic Chemistry Division-I, Indian Institute of Chemical Technology,
Hyderabad – 500007, India (Fax: þ 91-40-27160512; e-mail: hmmeshram@yahoo.com)
Polyethylene glycol (PEG) has been reported as an efficient and convenient medium for the three-
component synthesis for spiro-oxindole.
Introduction. – The indole moiety constitutes a core structure of many therapeuti-
cally active compounds [1]. It is also found in many biologically active natural products
[2]. For example, spirotryprostatin-A has been found as a novel inhibitor of microtubili
assembly [3], and pteropodine and isopterodine have been shown to modulate the
function of muscarinic serotonin receptors [4]. Because of their conformational rigidity,
they confer favorable physiological properties for bioavailability. Hence, they have
found application as pharmaceuticals.
Synthesis of spiro-oxindoles has been reported by three-component reaction of
isatin, malononitrile, and naphthol in the presence of InCl3 [5]. A synthesis of spiro-
oxindoles is also accomplished using microwave [6]. Recently, tetrabutylammonium
fluoride (Bu4NF) has been described as a catalyst for a three-component reaction [7].
Results and Discussion. – Recently, polyethylene glycol (PEG) has attracted
interest as solvent [8] because of its unique properties like low cost, reduced toxicity,
recyclability, reduced inflammability, easy degradability, and miscibility with a wide
variety of organic solvents. Encouraged by this advantage of PEG, we planned to
synthesize spiro-oxindoles using PEG as a medium. Here, we report the results of PEG-
mediated synthesis of spiro-oxindoles (Scheme 1).
ꢀ 2010 Verlag Helvetica Chimica Acta AG, Zꢁrich

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Scheme 1
To optimize the reaction conditions, a mixture of isatin, malononitrile, and
dimedone was stirred with 0.3 ml of PEG at room temperature. TLC showed formation
of a product in low yield (10%). Therefore, the same mixture was heated at 508 for
60 min to accomplish the reaction. After workup, spiro-oxindole was the only product
isolated in high yield. We noticed also that reducing in the quantity of PEG (0.1 ml)
decreased the efficiency of the reaction. To study the electronic effect of substituents on
the reaction, we have examined a variety of substrates. It was observed that electron-
withdrawing substituents reduce efficiency of the reaction, whereas electron-donating
substituents facilitate the reaction. For example, the reaction of 5-nitroisatin (Table 1,
Entry 9) under optimized conditions resulted in 86% yield of the spiro-oxindole 9,
whereas 5-methylisatin (Entry 5) gave 90% yield of expected product 5 in short time
(60 min).
It was also noticed that substituents on the N-atom increase the efficiency of the
reaction. For example, N-substituted isatins (Entries 10 – 13) reacted with malononi-
trile and dimedone in presence of PEG to afford the corresponding products 10 – 13 in
high yield in short time (45 min).
Table 1. PEG-400-Catalyzed Three-Component Synthesis of Spiro-oxindoles 1 – 13
Entry
Compound
R
R1
R2
Time [min]
Yield [%]
1
2
3
4
5
6
7
8
9
10
11
12
13
1
2
3
4
5
6
7
8
9
10
11
12
13
H
H
H
H
H
H
H
H
H
COOMe
COOMe
COOMe
CN
CN
CN
CN
CN
CN
CN
80
70
80
60
60
60
60
65
80
45
45
45
50
87
89
82
92
90
91
87
89
86
92
93
91
88
6-Br
7-Cl
H
5-Me
4-Br
6-Br
7-Cl
5-NO2
H
H
PhCH2
Me
Ph
Ac
H
H
H
CN
CN
CN

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Helvetica Chimica Acta – Vol. 93 (2010)
After these encouraging results, we further tested this protocol for barbituric acid
and 4-hydroxycoumarin. The reaction of isatin (Table 2, Entries 1 – 3), malononitrile,
and barbituric acid proceeded smoothly leading to the corresponding products 14 – 16
in good yield. Analogously, 4-hydroxycoumarin reacted with isatins (Entries 4 – 6)
under optimized conditions and gave the expected products 17 – 19 again in high yields.
Scheme 2
Table 2. PEG-400-Catalyzed Three-Component Synthesis of Spiro-oxindoles 14 – 19
Entry
Compound
R
R1
R2
Time [min]
Yield [%]
1
2
3
4
5
6
14
15
16
17
18
19
H
H
4-Br
H
H
Me
H
H
H
H
COOMe
CN
CN
COOMe
CN
CN
85
90
80
85
80
85
88
91
90
85
87
87
H
Me
Conclusions. – We have developed a general and efficient method using PEG as an
efficient and convenient medium for the three-components synthesis of spiro-
oxindoles. The products are isolated in high yield. Easy workup, high yield, and
inexpensive catalyst are the advantages of the present procedure.
The authors D. A. K., B. R. V. P., and P. R. G. thank CSIR and UGC New Delhi for fellowships.
Experimental Part
General. All reactions were carried out without any special precautions in an atmosphere of air.
Chemicals were purchased from Fluka and S. D. Fine Chemicals. TLC: Precoated silica-gel plates (60
F254, 0.2-mm layer; E. Merck). 1H-NMR Spectra: Varian 200 or Bruker 300 spectrometer; in (D6)DMSO;
d in ppm, J in Hz. MS: VG Autospec; in m/z.
General Procedure. To a suspension of isatin (1 mmol) in PEG (0.3 ml), malononitrile (1 mmol) and
dimedone (1 mmol) were added. This mixture was stirred at 508 until completion of the reaction
(monitored by TLC). The mixture was diluted with H2O, and the solid was filtered off and again washed
with H2O to obtain the purified product. The compounds were recrystallized from appropriate solvents.
The products thus obtained were characterized by means of IR, NMR, and MS.
Methyl
2-Amino-1’,2’,5,6,7,8-hexahydro-7,7-dimethyl-2’,5-dioxospiro[4H-1-benzopyran-4,3’-
[3H]indole]-3-carboxylate (1). White solid. M.p. 255 – 2568. IR: 3366, 3241, 3187, 2955, 1690, 1614,

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1
1520, 1471, 1304, 1225, 1167, 1054, 928, 746. H-NMR: 10.22 (s, NH); 7.88 (br. s, NH2); 7.05 – 7.11 (m, 1
arom. H); 6.90 (d, J ¼ 6.0, 1 arom. H); 6.82 (t, J ¼ 7.8, 1 arom. H); 6.76 (d, J ¼ 6.9, 1 arom. H); 3.32 (s,
Me); 2.66 (d, J ¼ 17.4, CH); 2.55 (d, J ¼ 17.4, CH); 2.23 (d, J ¼ 15.66, CH); 2.07 (d, J ¼ 15.66, CH); 1.10 (s,
Me); 1.01 (s, Me). EI-MS: 368 (Mþ). Anal. calc. for C20H20N2O5: C 65.21, H 5.47, N 7.60; found: C 65.47,
H 5.35, N 7.68.
Methyl 2-Amino-6’-bromo-1’,2’,5,6,7,8-hexahydro-7,7-dimethyl-2’,5-dioxospiro[4H-1-benzopyran-
4,3’-[3H]indole]-3-carboxylate (2). White solid. M.p. 270 – 2728. IR: 3356, 3280, 3124, 2943, 1721, 1686,
1617, 1538, 1411, 1303, 1217, 1142, 1058, 917. 1H-NMR: 10.30 (s, NH); 7.82 (br. s, NH2); 6.94 (d, J ¼ 10.4, 1
arom. H); 6.70 – 6.82 (m, 2 arom. H); 3.30 (s, Me); 2.59 (d, J ¼ 20.0, 1 H, CH2); 2.48 (d, J ¼ 20.0, 1 H,
CH2); 2.16 (d, J ¼ 21.2, CH); 2.02 (d, J ¼ 21.6, CH); 1.02 (s, Me); 0.95 (s, Me). EI-MS: 446 (Mþ), 448
([M þ 2]þ). Anal. calc. for C20H19BrN2O5: C 53.71, H 4.28, N 6.26; found: C 53.96, H 4.31, N 6.19.
Methyl 2-Amino-7’-chloro-1’,2’,5,6,7,8-hexahydro-7,7-dimethyl-2’,5-dioxospiro[4H-1-benzopyran-
4,3’-[3H]indole]-3-carboxylate (3). White solid. M.p. 279 – 2808. IR: 3365, 3280, 3119, 2990, 1717, 1679,
1
1616, 1520, 1416, 1315, 1214, 1130, 1042, 898, 730, 642, 555. H-NMR: 10.50 (s, NH); 7.84 (br. s, NH2);
7.10 – 7.14 (m, 1 arom. H); 6.73 – 6.79 (m, 2 arom. H); 3.25 (s, Me); 2.42 – 2.6 (m, CH2); 2.13 (d, J ¼ 21.2,
CH); 2.05 (d, J ¼ 21.2, CH); 1.04 (s, Me); 0.95 (s, Me). EI-MS: 402 (Mþ). Anal. calc. for C20H19ClN2O5: C
59.63, H 4.97, N 6.95; found: C 56.70, H 4.64, N 6.83.
2-Amino-1’,2’,5,6,7,8-hexahydro-7,7-dimethyl-2’,5-dioxospiro[4H-1-benzopyran-4,3’-[3H]indole]-3-
carbonitrile (4). White solid. M.p. 287 – 2898. IR: 3380, 3308, 3142, 2195, 1723, 1659, 1608, 1466, 1350,
1219, 1059, 908, 748. 1H-NMR: 10.41 (s, NH); 7.22 (br. s, NH2); 7.11 (t, J ¼ 10.0, 1 arom. H); 7.01 – 6.73 (m,
3 arom. H); 2.56 (s, CH2); 2.23 – 2.03 (m, CH2); 1.03 (s, Me); 1.00 (s, Me). EI-MS: 335 (Mþ). Anal. calc.
for C19H17N3O3: C 68.05, H 5.11, N 12.53; found: C 68.24, H 5.22, N 12.61.
2-Amino-1’,2’,5,6,7,8-hexahydro-5’,7,7-trimethyl-2’,5-dioxospiro[4H-1-benzopyran-4,3’-[3H]indole]-
3-carbonitrile (5). White solid. M.p. 277 – 2798. IR: 3364, 3310, 3143, 2967, 2192, 1721, 1659, 1607, 1497,
1350, 1221, 1165, 1049, 914. 1H-NMR: 10.24 (s, NH); 7.16 (br. s, NH2); 6.92 (d, J ¼ 10.4, 1 arom. H); 6.76
(s, 1 arom. H); 6.67 (d, J ¼ 7.6, 1 arom. H); 2.51 – 2.55 (m, CH2); 2.18 (s, Me); 2.10 – 2.15 (m, CH2); 1.02 (s,
Me); 0.99 (s, Me ). EI-MS: 349 (Mþ). Anal. calc. for C20H19N3O3: C 68.75, H 5.48, N 12.03; found: C
68.56, H 5.57, N 12.11.
2-Amino-4’-bromo-1’,2’,5,6,7,8-hexahydro-7,7-dimethyl-2’,5-dioxospiro[4H-1-benzopyran-4,3’-[3H]-
indole]-3-carbonitrile (6). White solid. M.p. 312 – 3158. IR: 3363, 3310, 3152, 2962, 2199, 1724, 1659, 1605,
1497, 1350, 1219, 1048, 928. 1H-NMR: 10.41 (s, NH); 7.28 (br. s, NH2); 7.14 (t, J ¼ 7.6, 1 arom. H); 6.98 (d,
J ¼ 7.2, 1 arom. H); 6.78 (d, J ¼ 7.6, 1 arom. H); 2.56 (d, J ¼ 7.6, CH2); 2.17 (d, J ¼ 15.6, CH); 2.08 (d, J ¼
16.0, CH); 1.03 (s, Me); 1.00 (s, Me). EI-MS: 413 (Mþ), 415 ([M þ 2]þ). Anal. calc. for C19H16BrN3O3: C
55.09, H 3.89, N 10.14; found: C 55.19, H 3.97, N 10.19.
2-Amino-6’-bromo-1’,2’,5,6,7,8-hexahydro-7,7-dimethyl-2’,5-dioxospiro[4H-1-benzopyran-4,3’-[3H]-
indole]-3-carbonitrile (7). White solid. M.p. 318 – 3208. IR: 3357, 3312, 3170, 1721, 1667, 1605, 1486, 1358,
1219, 1049, 918, 802. 1H-NMR: 10.59 (s, NH); 7.35 (br. s, NH2); 7.09 (d, J ¼ 7.6, 1 arom. H); 6.93 (s, 1 arom.
H); 6.78 (d, J ¼ 7.6, 1 arom. H); 2.53 (d, J ¼ 7.6, CH2); 2.17 (d, J ¼ 16.0, CH); 2.10 (d, J ¼ 16.0, CH); 1.02
(s, Me); 1.00 (s, Me). EI-MS: 413 (Mþ), 415 ([M þ 2]þ). Anal. calc. for C19H16BrN3O3: C 55.09, H 3.89, N
10.14; found: C 55.34, H 3.26, N 10.22.
2-Amino-7’-chloro-1’,2’,5,6,7,8-hexahydro-7,7-dimethyl-2’,5-dioxospiro[4H-1-benzopyran-4,3’-[3H]-
indole]-3-carbonitrile (8). White solid. M.p. 278 – 2808. IR: 3352, 3315, 3152, 2960, 2189, 1729, 1675, 1605,
1490, 1352, 1225, 1042, 910, 807, 744, 665, 572. 1H-NMR: 10.45 (s, NH); 7.42 (br. s, NH2); 7.13 – 7.23 (m, 1
arom. H); 6.79 – 6.87 (m, 2 arom. H); 2.49 – 2.54 (m, CH2); 2.02 – 2.13 (m, CH2); 1.04 (s, Me); 0.95 (s,
Me). EI-MS: 369.5 (Mþ). Anal. calc. for C19H16ClN3O3: C 61.71, H 4.36, N 11.36; found: C 61.80, H 4.56,
N 11.63.
2-Amino-1’,2’,5,6,7,8-hexahydro-7,7-dimethyl-5’-nitro-2’,5-dioxospiro[4H-1-benzopyran-4,3’-[3H]-
indole]-3-carbonitrile (9). White solid. M.p. 302 – 3048. IR: 3390, 3252, 3197, 2959, 2876, 2190, 1741, 1681,
1645, 1473, 1343, 1289, 1224, 1168, 1061, 913. 1H-NMR: 11.44 (s, NH); 8.39 – 8.46 (m, 1 arom. H); 8.21 –
8.27 (m, 1 arom. H); 7.79 (br. s, NH2); 7.31 (d, J ¼ 8.6, 1 arom. H); 2.81 – 2.94 (m, CH2); 2.35 – 2.51 (m,
CH2); 1.29 (s, 2 Me). EI-MS: 380 (Mþ). Anal. calc. for C19H16N4O5: C 60.0, H 4.24, N 14.73; found: C
60.28, H 4.35, N 14.64.

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2-Amino-1’,2’,5,6,7,8-hexahydro-7,7-dimethyl-2’,5-dioxo-1’-(phenylmethyl)spiro[4H-1-benzopyran-
4,3’-[3H]indole]-3-carbonitrile (10). White solid. M.p. 267 – 2698. IR: 3384, 3320, 3204, 2962, 2198, 1713,
1668, 1612, 1487, 1352, 1229, 1168, 1052, 894, 744. 1H-NMR: 7.47 (d, J ¼ 9.6, 2 arom. H); 7.21 – 7.35 (m, 3
arom. H, NH2); 7.05 – 7.14 (m, 2 arom. H); 6.94 (t, J ¼ 10.0, 1 arom. H); 6.67 (d, J ¼ 10.0, 1 arom. H); 4.88
(d, J ¼ 7.6, CH2); 2.53 – 2.59 (m, CH2); 2.22 (d, J ¼ 21.2, CH); 2.10 (d, J ¼ 21.2, CH); 1.03 (s, Me); 1.00 (s,
Me). EI-MS: 425 (Mþ). Anal. calc. for C26H23N3O3: C 73.39, H 5.45, N 9.88; found: C 73.66, H 5.34, N
9.97.
2-Amino-1’,2’,5,6,7,8-hexahydro-1’,7,7-trimethyl-2’,5-dioxospiro[4H-1-benzopyran-4,3’-[3H]indole]-
3-carbonitrile (11). White solid. M.p. 253 – 2558. IR: 3377, 3318, 3172, 2959, 2194, 1705, 1678, 1608, 1493,
1355, 1227, 1165, 1052, 903. 1H-NMR: 7.24 (br. s, NH2); 7.19 – 7.22 (m, 1 arom. H); 6.93 – 7.04 (m, 3 arom.
H); 3.12 (s, Me); 2.50 – 2.55 (m, CH2); 2.04 – 2.16 (m, CH2); 1.02 (s, Me); 0.98 (s, Me). EI-MS: 349 (Mþ).
Anal. calc. for C20H19N3O3: C 68.75, H 5.48, N 12.03; found: C 69.01, H 5.39, N 12.12.
2-Amino-1’,2’,5,6,7,8-hexahydro-7,7-dimethyl-2’,5-dioxo-1’-phenylspiro[4H-1-benzopyran-4,3’-[3H]-
indole]-3-carbonitrile (12). White solid. M.p. 304 – 3068. IR: 3430, 3310, 2955, 2192, 1713, 1655, 1500,
1465, 1350, 1319, 1218, 1052. 1H-NMR: 7.84 (t, J ¼ 7.7, 2 arom. H); 7.71 (t, J ¼ 7.36, 1 arom. H); 7.59 – 7.63
(m, 2 arom. H, NH2); 7.37 – 7.46 (m, 2 arom. H); 7.28 (t, J ¼ 7.36, 1 arom. H); 6.89 (d, J ¼ 7.74, 1 arom. H);
2.71 – 2.76 (m, CH2); 2.34 – 2.51 (m, CH2); 1.29 (s, Me); 1.26 (s, Me). EI-MS: 411 (Mþ). Anal. calc. for
C25H21N3O3: C 72.98, H 5.14, N 10.21; found: C 72.74, H 5.25, N 10.29.
1’-Acetyl-2-amino-1’,2’,5,6,7,8-hexahydro-7,7-dimethyl-2’,5-dioxospiro[4H-1-benzopyran-4,3’-[3H]-
indole]-3-carbonitrile (13). Yellow solid. M.p. 248 – 2518. IR: 3409, 3325, 3245, 3195, 2966, 2905, 2193,
1717, 1685, 1658, 1597, 1462, 1353, 1264, 1165, 1043, 967, 912, 793, 770, 592, 516, 515. 1H-NMR: 8.04 (d, J ¼
8.48, 1 H); 7.49 (s, NH2); 7.33 – 7.28 (m, 1 arom. H); 7.19 (d, J ¼ 3.7, 2 arom. H); 2.64 (d, J ¼ 1.5, CH2);
2.55 (s, Me); 2.15 – 2.18 (m, CH2); 1.02 (s, Me); 1.00 (s, Me); 1.02 (s, Me); 0.95 (s, Me). EI-MS: 377.13
(Mþ). Anal. calc. for C21H19N3O4: C 66.8, H 5.07, N 11.13; found: C 66.83, H 5.05, N 11.15.
Methyl
2’-Amino-1,2-dihydro-1-methyl-2,5’-dioxospiro[3H-indole-3,4’-[4H,5H]pyrano[3,2-
c][1]benzopyran]-3’-carboxylate (14). White solid. M.p. 244 – 2468. IR: 3503, 3426, 3318, 3160, 2202,
1692, 1654, 1578, 1468, 1390, 1188, 1134, 826, 771. 1H-NMR: 12.53 (br. s, NH); 12.04 (br. s, NH); 10.92 (br.
s, NH); 7.88 (br. s, NH2); 7.14 (t, J ¼ 10.0, 1 arom. H); 6.98 (d, J ¼ 10.4, 1 arom. H); 6.81 – 6.86 (m, 2 arom.
H); 3.21 (s, Me); 3.08 (s, Me). EI-MS: 370 (Mþ). Anal. calc. for C17H14N4O6: C 55.14, H 3.81, N 15.13;
found: C 55.27, H 3.74, N 15.27.
2’-Amino-1,2-dihydro-2,5’-dioxospiro[3H-indole-3,4’-[4H,5H]pyrano[3,2-c][1]benzopyran]-3’-car-
bonitrile (15). White solid. M.p. 273 – 2748. IR: 3448, 3280, 3142, 3033, 2204, 1697, 1643, 1511, 1443, 1396,
1242, 1114, 1003, 846, 663. 1H-NMR: 12.40 (br. s, NH); 12.02 (br. s, NH); 10.52 (br. s, NH); 7.41 (br. s,
NH2); 7.17 (t, J ¼ 8.0, 2 arom. H); 6.91 (t, J ¼ 7.6, 1 arom. H); 6.79 (d, J ¼ 7.6, 1 arom. H). EI-MS: 323
(Mþ). Anal. calc. for C15H9N5O4: C 55.73, H 2.81, N 21.66; found: C 55.40, H 2.89, N 21.68.
2’-Amino-4-bromo-1,2-dihydro-2,5’-dioxospiro[3H-indole-3,4’-[4H,5H]pyrano[3,2-c][1]benzopyr-
an]-3’-carbonitrile (16). White solid. M.p. 253 – 2558. IR: 3502, 3420, 3325, 2198, 1690, 1657, 1580, 1472,
1385, 1340, 1250, 1185, 1065, 776. 1H-NMR: 12.62 (br. s, NH); 12.22 (br. s, NH); 10.30 (br. s, NH); 7.02 (t,
J ¼ 8.0, 1 arom. H); 6.95 (d, J ¼ 8.0, 1 arom. H); 6.89 (br. s, NH2); 6.71 (d, J ¼ 7.6, 1 arom. H). EI-MS: 401
(Mþ), 403 ([M þ 2]þ). Anal. calc. for C15H8BrN5O4: C 44.80, H 2.01, N 17.41; found: C 44.66, H 2.09, N
17.49.
Methyl 7’-Amino-1,1’,2,2’,3’,4’-hexahydro-2,2’,4’-trioxospiro[3H-indole-3,5’-[5H]pyrano[2,3-d]pyri-
midine]-6’-carboxylate (17). White solid. M.p. 273 – 2758. IR: 3380, 3312, 3094, 1712, 1668, 1613, 1530,
1443, 1288, 964, 910, 760, 665. 1H-NMR: 10.42 (s, NH); 8.02 (br. s, NH2); 8.04 (d, J ¼ 8.0, 1 arom. H); 7.74
(t, J ¼ 8.0, 1 arom. H); 7.53 (t, J ¼ 7.6, 1 arom. H); 7.45 (d, J ¼ 8.4, 1 arom. H); 7.11 (t, J ¼ 7.6, 1 arom. H);
7.01 (d, J ¼ 7.2, 1 arom. H); 6.79 (t, J ¼ 7.6, 1 arom. H); 6.75 (d, J ¼ 7.6, 1 arom. H); 3.22 (s, Me). EI-MS:
390 (Mþ). Anal. calc. for C21H14N2O6: C 64.62, H 3.62, N 7.18; found: C 64.84, H 3.55, N 7.11.
7’-Amino-1,1’,2,2’,3’,4’-hexahydro-2,2’,4’-trioxospiro[3H-indole-3,5’-[5H]pyrano[2,3-d]pyrimidine]-
6’-carbonitrile (18). White solid. M.p. 290 – 2928. IR: 3350, 3300, 3195, 2954, 2199, 1720, 1667, 1613, 1522,
1474, 1364, 1224, 1132, 1072, 972, 748. 1H-NMR: 10.64 (s, NH); 7.95 (d, J ¼ 8.0, 1 arom. H); 7.77 (t, J ¼ 7.6,
1 arom. H); 7.67 (br. s, NH2); 7.57 (t, J ¼ 7.6, 1 arom. H); 7.50 (d, J ¼ 8.4, 1 arom. H); 7.22 (t, J ¼ 7.6, 2
arom. H); 6.93 (t, J ¼ 7.6, 1 arom. H); 6.85 (d, J ¼ 8.0, 1 arom. H). EI-MS: 357 (Mþ). Anal. calc. for
C20H11N3O4: C 67.23, H 3.10, N 11.76; found: C 67.49, H 3.02, N 11.86.

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7’-Amino-1,1’,2,2’,3’,4’-hexahydro-1-methyl-2,2’,4’-trioxospiro[3H-indole-3,5’-[5H]pyrano[2,3-d]pyr-
imidine]-6’-carbonitrile (19). White solid. M.p. 285 – 2868. IR: 3408, 3300, 3192, 2195, 1716, 1670, 1612,
1468, 1237, 1116, 1059, 968, 754. 1H-NMR: 7.93 (d, J ¼ 10.8, 1 arom. H); 7.76 (t, J ¼ 10.8, 1 arom. H); 7.71
(br. s, NH2); 7.55 (t, J ¼ 10.8, 1 arom. H); 7.49 (d, J ¼ 10.8, 1 arom. H); 7.26 – 7.34 (m, 2 arom. H); 6.98 –
7.08 (m, 2 arom. H); 3.19 (s, Me). EI-MS: 371 (Mþ). Anal. calc. for C21H13N3O4: C 67.92, H 3.53, N 11.32;
found: C 67.65, H 3.65, N 11.23.
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Received July 21, 2009