Ethyl 2-cyano-3-(naphth-1-ylamino)-3-thioxopropanoate (2e) was prepared as described for the 2a
derivative, using 1-naphthyl isothiocyanate (18.5 g, 0.1 mol) and stirring for a further 5 h after addition of
1-naphthyl isothiocyanate to give the desired product (22.6 g, 79%) as yellow needles; mp 131-132°C. FT-IR
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spectrum, ν, cm–1: 3400 (N–H), 2991, 2203, 1651 (C=O), 1570, 1375, 1277, 777. H NMR spectrum, δ, ppm
(J, Hz): 1.41 (3H, t, J = 7.2, CH3); 4.34 (2H, q, J = 7.2, CH2); 4.62 (1H, s, CH); 7.45-7.66 (4H, m, Ar); 7.89–
7.96 (3H, m, Ar); 11.98 (1H, br. s, exchanged by D2O addition, NH). 13C NMR spectrum, δ, ppm: 14.42, 61.14,
73.01, 119.04, 121.98, 125.07, 125.23, 127.25, 127.80, 128.60, 129.51, 129.58, 133.22, 134.36, 168.03, 170.64.
MS (EI), m/z (Irel, %): 298 [M]+, (14), 295 (100), 292 (64), 281 (24), 263 (29), 236 (16), 196 (13), 164 (19).
Found, %: C 64.30; H 4.83; N 9.10. C16H14N2O2S. Calculated, %: C 64.41; H 4.73; N 9.39.
Ethyl 5-amino-3-(phenylamino)isoxazole-4-carboxylate (3a). Potassium hydroxide (6 g, 0.1 mol) was
slowly added to a solution of hydroxylamine hydrochloride (7.08 g, 0.1 mol) in water (30 ml). Ethanol (80 ml)
was added and the resulting potassium chloride was filtered off. Propanoate 2a (2.47 g, 0.01 mol) was added to
the filtrate and the mixture was refluxed for 24 h, water (80 ml) was added to the reaction mixture and the white
precipitate was collected by vacuum filtration. The white solid was recrystallized from ethanol to give the
desired product (2.42 g, 97%) as white needles; mp 167-168°C. FT-IR spectrum, ν, cm–1: 3481 (N–H), 3268
(NH2), 1667 (C=O), 1654, 1606, 1559, 1120, 779, 746. 1H NMR spectrum, δ, ppm (J, Hz): 1.29 (3H, t, J = 7.2,
CH3); 4.24 (2H, q, J = 7.2, CH2); 6.94 (1H, t, J = 7.2, Ar); 7.30 (2H, t, J = 7.5, Ar); 7.44 (2H, d, J = 7.2, Ar);
7.79 (2H, br. s, exchanged by D2O addition, NH2); 8.10 (1H, s, exchanged by D2O addition, NH). 13C NMR
spectrum, δ, ppm: 14.87, 60.01, 77.09, 117.83, 121.47, 129.41, 140.33, 159.41, 163.52, 169.75 (C=O). Mass
spectrum (EI), m/z (Irel, %): 247 [M]+ (58), 246 (100), 201 (14), 200 (20), 159 (43), 157 (95), 131 (36), 129 (73),
102 (57), 90 (73), 78 (27), 77 (27), 65 (58). Found, %: C 58.11; H 5.67; N 16.70. C12H13N3O3. Calculated, %:
C 58.29; H 5.30; N 16.99.
Ethyl 5-amino-3-(2-bromophenylamino)isoxazole-4-carboxylate (3b) was prepared as described for
compound 3a, using ethyl propanoate 2b (3.27 g, 0.01 mol) and refluxing for 48 h, to give the desired product
(2.63 g, 80%) as white needles; mp 155-156°C. FT-IR spectrum, ν, cm–1: 3480 (N–H), 3281 (NH2), 1654
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(C=O), 1599, 1584, 1555, 1458, 1442, 1129, 1022, 782, 742. H NMR spectrum, δ, ppm (J, Hz): 1.31 (3H, t,
J = 7.2, CH3); 4.29 (2H, q, J = 7.2, CH2); 6.90 (1H, td, J = 7.2, J = 1.5, Ar); 7.38 (1H, td, J = 8.1, J = 1.2, Ar);
7.63 (1H, dd, J = 7.8, J = 1.2, Ar); 7.90 (2H, br. s, exchanged by D2O addition, NH2), 8.06 (1H, dd, J = 8.6,
J = 1.5, Ar), 8.69 (1H, br. s, exchanged by D2O addition, NH). 13C NMR spectrum, δ, ppm: 14.86, 60.62, 77.21,
119.25, 122.32, 126.56, 128. 58, 132.29, 138.82, 157.75, 163.22, 172.34 (C=O). Found, %: C 44.43; H 3.67;
N 12.76. C12H12BrN3O3. Calculated, %: C 44.19; H 3.71; N 12.88.
Ethyl 5-amino-3-(3-bromophenylamino)isoxazole-4-carboxylate (3c) was prepared as described for
compound 3a, using compound 2c (3.27 g, 0.01 mol) and refluxing for 48 h, to give the desired product (2.9 g,
88%) as white needles; mp 160-161°C. FT-IR spectrum, ν, cm–1: 3481 (N–H), 3269 (NH2), 1650 (C=O), 1604,
1578, 1552, 1467, 1120, 773. 1H NMR spectrum, δ, ppm (J, Hz): 1.30 (3H, t, J = 7.2, CH3); 4.26 (2H, q, J = 7.2,
CH2); 7.10 (1H, br. d, J = 7.8, Ar); 7.24 (1H, t, J = 8.1, Ar); 7.41 (1H, d, J = 7.5, Ar); 7.80 (1H, s, Ar); 7.85 (2H,
s, exchanged by D2O addition, NH2); 8.23 (1H, s, exchanged by D2O addition, NH). 13C NMR spectrum, δ, ppm:
14.88, 60.07, 77.21, 117.05, 120.27, 122.29, 124.05, 131.22, 141.92, 159.17, 163.30, 169.86. Mass spectrum
(EI), m/z (Irel, %): 327 [M+2]+ (50), 325 [M+2]+ (50), 281 (10), 279 (10), 200 (16), 173 (20), 171 (21), 157
(100), 118 (14), 92 (27), 90 (88), 64 (39), 62 (40). Found, %: C 44.40; H 3.56; N 12.65. C12H12BrN3O3.
Calculated, %: C 44.19; H 3.71; N 12.88.
Ethyl 5-amino-3-(4-bromophenylamino)isoxazole-4-carboxylate (3d) was prepared as described for
compound 3a, using compound 2d (3.27 g, 0.01 mol) and refluxing for 48 h to give the desired product (2.6 g,
79%) as white needles; mp 160-161°C. FT-IR spectrum, ν, cm–1: 3469 (N–H), 3275 (NH2), 1667 (C=O), 1652,
1600, 1556, 1476, 1112, 781. 1H NMR spectrum, δ, ppm (J, Hz): 1.30 (3H, t, J = 7.2, CH3); 4.28 (2H, q, J = 7.2,
CH2); 7.25–7.56 (4H, m, Ar); 7.82 (2H, br. s, exchanged by D2O addition, NH2); 8.19 (1H, s, exchanged by D2O
addition, NH). 13C NMR spectrum, δ, ppm: 14.88, 60.04, 77.18, 112.91, 120.06, 132.02, 139.77, 159.24,
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