J. Bergman et al. / Tetrahedron 59 (2003) 1033–1048
1047
CH2), 2.27 (3H, s, CH3), 2.24 (3H, s, CH3); 13C NMR d: 174.6
(s), 150.5 (s), 142.3 (s), 141.6 (s), 140.1 (s), 132.5 (d), 131.7 (s),
131.4 (d), 128.2 (d), 126.7 (s), 126.4 (s), 126.0 (d), 125.5 (d),
125.4 (d), 124.3 (d), 123.6 (d), 121.1 (s), 116.2 (s), 114.3 (d),
110.4 (d), 75.1 (s), 43.7 (t), 20.5 (q), 20.3 (q). HRMS (FAB):
[MþH]þ, found 381.1707. C24H21N4O requires 381.1715.
4.4.10. 3-(20-Acetamidophenyl)-1,5-dihydro-1,4-benzo-
diazepin-2(2H)-one (59). A mixture of N-acetylisatin
(9.46 g, 50 mmol) and 2-aminobenzylamine (6.11 g,
50 mmol) was stirred at room temperature in acetic acid
(250 mL) for 7 days. The reaction mixture was basified with
NaOH (2 M). The solid formed was collected by filtration
and recrystallized from CH2Cl2. Yield: 6.18 g (42%); mp:
233–2348C; IR (KBr) nmax: 3179, 3074, 2968, 2900, 1676,
1660, 1603, 1577, 1538, 1445, 1315, 752 cm21; 1H NMR d:
11.12 (1H, s, NH), 10.86 (1H, s, NH), 7.88 (1H, d, J¼
7.8 Hz, Ph), 7.50–7.30 (4H, m, Ph), 7.20–7.10 (3H, m, Ph),
4.66 (2H, s, CH2), 1.97 (3H, s, CH3); 13C NMR d: 168.1 (s),
164.6 (s), 164.2 (s), 137.7 (s), 137.0 (s), 132.0 (s), 130.5 (d),
130.4 (d), 128.6 (d), 128.5 (d), 126.0 (s), 124.3 (d), 123.3
(d), 122.2 (d), 120.8 (d), 53.2 (t), 23.9 (q). HRMS (FAB):
[MþH]þ, found 294.1252. C17H16N3O2 requires 294.1242.
4.4.7. 1,2,3,4-Tetrahydroquinazolin-4-one-2-spiro-30-
1H-indolin-2-one (53a). Isatin (7.35 g, 50 mmol) and
2-aminobenzamide (6.80 g, 50 mmol) were dissolved in
hot acetic acid (70 mL) and then heated at reflux for 3 h,
whereupon the clear solution was evaporated. The residue
treated with 2-propanol gave a whitish solid. The analytical
sample was recrystallized from EtOH. Yield: 10.70 g
(81%); mp: 247–2498C; IR (KBr) nmax: 3490, 3233, 1712,
1649, 1622, 1474, 759 cm21; 1H NMR d: 10.28 (1H, s, NH),
8.33 (1H, s, NH), 7.59 (1H, d, J¼7.3 Hz, Ph), 7.47 (1H, d,
J¼7.3 Hz, Ph), 7.32 (1H, t, J¼7.7 Hz, Ph), 7.27 (1H, s, NH),
7.21 (1H, t, J¼8.1 Hz, Ph), 7.05 (1H, t, J¼7.4 Hz, Ph), 6.84
(1H, d, J¼7.7 Hz, Ph), 6.67 (1H, t, J¼7.4 Hz, Ph), 6.60 (1H,
d, J¼8.1 Hz, Ph); 13C NMR d: 175.9 (s), 163.8 (s), 146.7 (s),
142.0 (s), 133.2 (d), 130.7 (d), 129.4 (s), 126.8 (d), 125.3
(d), 122.2 (d), 117.0 (d), 114.2 (s), 113.8 (d), 110.0 (d). 70.9
(s). HRMS (FAB): [MþH]þ, found 266.0938. C15H12N3O2
requires 266.0929.
4.4.11. 2-(20-Acetamidophenyl)-4,5-dihydro-1,4-benzo-
diazepin-3(3H)-one (60). A solution of 55 (3.11 g,
10 mmol) in acetic acid (50 mL) was stirred at room
temperature for 7 days. The solid formed was collected by
filtration. Yield: 1.23 g (42%); mp: 250–2558C (dec.); IR
(KBr) nmax: 3169, 3068, 2909, 2870, 1692, 1667, 1588,
1
1567, 1530, 1446, 1310, 1194, 778, 758, 744 cm21; H
NMR d: 11.13 (1H, s, NH), 9.01 (1H, t, 6.2, NH), 7.84 (1H,
d, J¼8.1 Hz, Ph), 7.80 (1H, d, J¼7.7 Hz, Ph), 7.6–7.4 (3H,
m, Ph), 7.39 (1H, d, J¼7.4 Hz, Ph), 7.3–7.2 (2H, m, Ph),
4.20 (1H, br s, CH2), 4.00 (1H, br s, CH2), 2.11 (3H, s, CH3);
13C NMR d: 168.6 (s), 163.6 (s), 162.4 (s), 145.5 (s), 138.1
(s), 131.3 (d), 131.1 (s), 131.1 (d), 128.8 (d), 127.5 (s), 127.4
(d), 126.7 (d), 126.3 (d), 123.9 (d), 122.9 (d), 41.4 (t), 23.9
(q). HRMS (FAB): [MþH]þ, found 294.1234. C17H16N3O2
requires 294.1242.
4.4.8. 1,2,3,4-Tetrahydroquinazolin-4-one-2-spiro-30-5,7-
dichloro-1H-indolin-2-one (53b).
5,7-Dichloroisatin
(10.80 g, 50 mmol) and 2-aminobenzamide (6.80 g,
50 mmol) were dissolved in hot acetic acid (70 mL) and
then heated at reflux for 3 h, whereupon the clear solution
was evaporated. The residue treated with 2-propanol gave a
whitish solid. Yield: 12.4 g (74%); mp: 277–2788C; IR
(KBr) nmax: 3248, 1736, 1636, 1614, 1460, 1167, 748 cm21
;
1H NMR d: 10.95 (1H, s, NH), 8.41 (1H, s, NH), 7.7–7.6
(2H, m, Ph), 7.52 (1H, d, J¼1.9 Hz, Ph), 7.39 (1H, s, NH),
7.25 (1H, t, J¼7.6 Hz, Ph), 6.71 (1H, t, J¼7.6 Hz, Ph), 6.59
(1H, d, J¼8.0 Hz, Ph); 13C NMR d: 175.7 (s), 163.4 (s),
146.2 (s), 139.0 (s), 133.5 (d), 132.5 (s), 129.9 (d), 126.8 (d),
126.7 (s), 124.2 (d), 117.5 (d), 114.9 (s), 114.0 (s), 113.8 (d).
71.6 (s). Anal. calcd for C15H9Cl2N3O2: C, 53.92; H, 2.71;
N, 12.58. Found: C, 54.08; H, 2.77; N, 12.42.
4.5. Collection and refinement of X-ray diffraction data
The data collections for the compound 48a was performed
with a Nicolet diffractometer equipped with Cu Ka radiation
and an Enraf-Nonius CAD4 diffractometer with Mo Ka
radiation. The data sets were corrected for absorption and
the structures were solved by direct methods and refined by
full-matrix least-squares including an extinction parameter
for compound 48a. Only crystals of poor quality could be
obtained from compound 48a and as the refinements gave
rather high R-values and large standard deviations only
crystal data is given below. The connectivity is, however,
undoubtedly that shown for the compound.
4.4.9. 2-(2-Acetylaminophenyl)-N-(2-aminobenzyl)-2-
oxoacetamide (58). N-Acetylisatin (9.46 g, 50 mmol) was
heated to reflux in ethanol (200 mL) for 3 h, whereupon
2-aminobenzylamine (6.11 g, 50 mmol) was added to the
solution at 58C. After completed addition the temperature
was slowly allowed to increase to room temperature. The
solid formed was collected by filtration. Yield: 12.4 g
(80%); mp: 150–1518C; IR (KBr) nmax: 3462, 3356, 3284,
Compound 48a. A crystal of dimensions 0.25£0.25£
0.40 mm3 was used for the data collection. Of the measured
2314 independent reflections, 1375 with I.2s(I) were used
in the refinements and gave R¼0.065 and Rw¼0.082 with
309 parameters. C22H16N4O, M¼352.40: Compound 48a,
3230, 1697, 1681, 1660, 1633, 1606, 1543, 1480, 752 cm21
;
1H NMR d: 10.52 (1H, s, NH), 9.09 (1H, t, J¼6.2 Hz, NH),
7.77 (1H, d, J¼7.5 Hz, Ph), 7.7–7.5 (2H, m, Ph), 7.22 (1H,
dd, J¼7.6,1.1 Hz, Ph), 7.07 (1H, dd, J¼7.5, 1.4 Hz, Ph),
6.97 (1H, dd, J¼7.6, 1.4 Hz, Ph), 6.64 (1H, dd, J¼8.0,
1.1 Hz, Ph), 6.52 (1H, dd, J¼7.3, 1.1 Hz, Ph), 5.10 (2H, s,
space group P21/c, a¼10.332(9), b¼14.938(4), c¼
3
˚
˚
11.654(8) A, b¼109.83(6)8, V¼1692(2) A , Z¼4, Dc¼
1.383 g cm23, 2umax¼458 (Mo Ka), T¼150 K.
NH2), 4.24 (2H, d, J¼6.2 Hz, CH2), 1.97 (3H, s, CH3); 13
C
NMR d: 190.9 (s), 168.8 (s), 163.6 (s), 146.1 (s), 138.2 (s),
133.8 (d), 131.3 (d), 129.2 (d), 128.0 (d), 124.3 (s), 123.4
(d), 121.4 (d), 121.2 (s), 115.8 (d), 114.7 (d), 39.1 (t), 23.7
(q). Anal. calcd for C17H17N3O3: C, 65.58; H, 5.50; N,
13.50. Found: C, 65.50; H, 5.58; N, 13.39.
Acknowledgements
We thank Professor E. W. Warnhoff, University of Western
Ontario, London, Canada and Professor W. Stadlbauer, Karl
Franzens University, Graz, Austria for kind submission of