´
H. Kwiecien and M. Szychowska
3608
1
4c: H NMR d 7.08 (br s, 1H, NH), 6.92 (d, J ¼ 8.8 Hz, 1H, Ar), 6.58–6.56
(m, 1H, Ar), 6.53–6.52 (m, 1H, Ar), 4.54 (dd, J ¼ 3.5, 10.6 Hz, 1H, CH2), 4.31
(t, J ¼ 4.5 Hz, 1H, CH), 4.09 (br s, 2H, OH), 3.92–3.87 (m, 1H, CH2), 3.76
(t, J ¼ 4.6 Hz, 4H, CH2), 3.48 (t, J ¼ 4.6 Hz, 4H, CH2), 2.01–1.95 (m, 2H,
CH2), 1.63–1.57 (m, 2H, CH2), 1.43–1.36 (m, 2H, CH2), 0.95 (t, J ¼ 7.3 Hz,
3H, CH3); 13C NMR 174.9, 148.3, 145.0, 132.8, 121.6, 113.4, 112.4, 83.4, 60.4,
55.4, 43.6, 32.7, 27.6, 22.5, 14.1. Anal. calcd. for C17H26N2O4 (322.40): C,
63.33; H, 8.13; N, 8.69, Found: C, 63.27; H, 8.22; N, 8.79.
1
4d: H NMR d 7.17 (br s, 1H, NH), 6.25 (s, 1H, Ar), 6.12 (s, 1H, Ar), 4.66
(d, J ¼ 13.6 Hz, 1H, CH2), 4.24 (t, J ¼ 3.6 Hz, 1H, CH), 3.80 (s, 3H,
OCH3), 3.77 (m, 4H, CH2), 3.70 (brs, 2H, OH), 3.68–3.63 (m, 1H, CH2),
3.47 (m, 4H, CH2), 2.15–2.00 (m, 2H, CH2), 1.16 (t, J ¼ 7.3 Hz, 3H, CH3);
13C NMR 175.1, 152.4, 145.7, 137.2, 135.1, 103.8, 98.3, 84.5, 60.3, 56.2,
55.4, 43.4, 26.7, 9.6. Anal. calcd. for C16H24N2O5 (324.37): C, 59.24; H,
7.46; N, 8.64, Found: C, 59.14; H, 7.51; N, 8.71.
4e: 1H NMR d 6.70 (br s, 1H, NH), 6.25 (d, J ¼ 2.4 Hz, 1H, Ar), 6.12 (d, J ¼
2.4 Hz, 1H, Ar), 4.70 (dd, J ¼ 3.0, 10.8 Hz, 1H, CH2), 4.30 (t, J ¼ 3.5 Hz, 1H,
CH), 3.82 (t, J ¼ 4.6 Hz, 4H, CH2), 3.80 (s, 3H, OCH3), 3.72–3.70 (m, 1H,
CH2), 3.53 (t, J ¼ 4.7 Hz, 4H, CH2), 3.50 (br s, 2H, OH), 2.10–1.98 (m, 2H,
CH2), 1.70–1.62 (m, 2H, CH2), 1.45–1.37 (m, 2H, CH2), 0.95 (t, J ¼ 7.3 Hz,
3H, CH3); 13C NMR 175.1, 152.5, 145.8, 137.4, 135.2, 103.8, 98.4, 83.7, 60.6,
56.1, 55.4, 43.6, 33.2, 27.4, 22.5, 14.1. Anal. calcd. for C18H28N2O5 (352.43):
C, 61.34; H, 8.01; N, 7.95, Found: C, 61.21; H, 8.12; N, 8.03.
REFERENCES
1. Lunsford, C. D.; Welstead, W. J.; Helsley, G. C.; Grover, C. Tranquilizing and
analgesic 1,3-disubstituted-pyrrolidines. A. H. Robins Co., Inc. Patent ZA
6705136; 1968. Chem. Abstr. 1969, 70, 356–357.
2. Cale, A. D., Jr.; Gero, T. W.; Walker, K. R.; Lo, Y. S.; Welstead, W. J.;
Jaques, L. W.; Johnson, A. F.; Leonard, C. A.; Nolan, J. C.; Johnson, D. N.
Benzo- and pyrido-1,4-oxazepin-5-ones and -thiones: Synthesis and structure–
activity relationships of a new series of H1 antihistamines. J. Med. Chem. 1989,
32, 2178–2199.
3. Kamei, K.; Maeda, N.; Ogino, R.; Koyama, M.; Nakajima, M.; Tatsuoka, T.;
Ohno, T.; Inoue, T. New 5-HT1A receptor agonists possessing 1,4-benzoxazepine
scaffold exhibit highly potent anti-ischemic effects. Bioorg. Med. Chem. Lett.
2001, 11, 595–598.
4. Walker, G. N.; Smith, R. T. Synthesis of 5-phenyl-2,3,4,5-tetrahydro-1,4-benz-
oxazepines and corresponding 3-ones. J. Org. Chem. 1971, 36, 305–308.
5. Stokker, G. E.; Deana, A. A.; deSolms, S. J.; Schultz, E. M.; Smith, R. L.;
Cragoe, E. J.; Baer, J. E.; Russo, H. F.; Watson, L. S. 2-(Aminomethyl)phenols,
a new class of saluretic agents,. 4: Effects of oxygen and/or nitrogen substitution.
J. Med. Chem. 1982, 25, 735–742.