The Journal of Organic Chemistry
Article
C14H16N2O4: C, 60.86; H, 5.84; N, 10.14. Found: C, 60.95; H, 5.97;
N, 10.01.
4H); 13C NMR (75 MHz, CDCl3) δC 185.8, 169.0, 160.9, 141.3,
135.7, 132.6, 131.6, 129.7, 129.0, 128.9, 127.5, 66.5, 66.1, 49.8, 46.1,
42.4, 39.9; MS m/z 401 (M + H)+; IR νmax/cm−1 (KBr) 3246, 3064,
1665, 1617, 1586, 1476, 1218, 858; mp 128−129 °C. Anal. Cacld for
C21H21ClN2O4: C, 62.92; H, 5.28; N, 6.99. Found: C, 63.04; H, 5.46;
N, 6.74.
N-Benzyl-2-(2-(4-methoxyphenyl)-2-oxoacetamido)-N-methyla-
cetamide (64). Starting material: 1,3-oxazol-2-oxime 150 mg (0.44
mmol). The crude material was purified by column chromatography
(PE/EtOAc 5:5) to give 133 mg of product as colorless oil (yield
88%). Mixture of rotamers, signals are referred to the main rotamer:
1H NMR (300 MHz, CDCl3) δH 8.35−8.31 (m, 2H), 8.05 (br s, NH),
7.38−7.14 (m, 5H), 6.94−6.89 (m, 2H), 4.61 (s, 2H), 4.24−4.20 (br t,
2H), 3.85 (s, 3H), 2.92 (s, 3H); 13C NMR (75 MHz, CDCl3) δC
185.4, 167.4, 164.7, 162.8, 136.4, 133.7, 129.2, 128.8, 127.8, 126.3,
113.9, 55.6, 51.3, 41.3, 33.7; MS m/z 341 (M + H)+; IR νmax/cm−1
(KBr) 3387, 3300, 1646, 1653, 1511, 1453, 1263, 1028. Anal. Calcd for
C19H20N2O4: C, 67.05; H, 5.92; N, 8.23. Found: C, 67.14; H, 6.12; N,
8.46.
N-(1-Morpholino-1-oxopropan-2-yl)-2-oxo-2-phenylacetamide
(58). Starting material: 1,3-oxazol-2-oxime 150 mg (0.55 mmol). The
crude material was purified by column chromatography (PE/EtOAc
3:7) to give 92 mg of product as yellow oil (yield 60%). Mixture of
1
rotamers, signals are referred to the main rotamer: H NMR (300
MHz, CDCl3) δH 8.20−8.17 (m, 2H), 8.03 (br d, NH), 7.56−7.38 (m,
3H), 4.80−4.72 (m, 1H), 3.64−3.35 (m, 4H), 1.98−1.78 (m, 4H),
1.39 (d, J = 6.9 Hz, 3H); 13C NMR (75 MHz, CDCl3) δC 187.5, 169.9,
161.6, 134.2, 133.23, 130.9, 128.4, 46.9, 46.4, 46.2, 26.0, 24.1, 17.9; MS
m/z 275 (M + H)+; IR νmax/cm−1 (KBr) 3253, 3062, 1638, 1667,
1510, 1449, 1264, 715. Anal. Calcd for C15H18N2O3: C, 65.68; H, 6.61;
N, 10.21. Found: C, 65.66; H, 6.65; N, 10.25.
2-(4-Chlorophenyl)-N-(1-morpholino-1-oxopropan-2-yl)-2-oxoa-
cetamide (59). Starting material: 1,3-oxazol-2-oxime 150 mg (0.49
mmol). The crude material was purified by column chromatography
(PE/EtOAc 4:6) to give 80 mg of product as colorless oil (yield 53%):
1H NMR (300 MHz, CDCl3) δH 8.25−8.23 (m, 2H, AA′XX′), 7.97
(br d, NH), 7.43−7.40 (m, 2H, AA′XX′), 4.77−4.72 (m, 1H), 3.66−
3.39 (m, 4H), 2.03−1.83 (m, 4H), 1.42 (d, J = 7.0 Hz, 3H);13C NMR
(75 MHz, CDCl3) δC 186.1, 169.9, 161.0, 141.1, 132.6, 131.8, 129.0,
47.1, 46.5, 46.3, 26.2, 24.2, 18.1; MS m/z 309 (M + H)+; IR νmax/cm−1
(KBr) 3239, 3062, 1670, 1668, 1586, 1455, 856. Anal. Calcd for
C15H17ClN2O3: C, 58.35; H, 5.55; N, 9.07. Found: C, 58.23; H, 5.21;
N, 9.2.
N-(2-(4-Methylpiperazin-1-yl)-2-oxoethyl)-2-oxo-2-p-tolylaceta-
mide (65). Starting material: 1,3-oxazol-2-oxime 150 mg (0.50 mmol).
The crude material was purified by column chromatography (DCM/
MeOH 97:3) to give the product as yellow solid (75 mg, 50% yield):
1H NMR (400 MHz, CDCl3) δH 8.19 (br d, 2H, AA′XX′), 7.92 (br s,
NH), 7.27−7.25 (m, 2H, AA′XX′) partially overlapped to the solvent,
4.17 (d, J = 4.2 Hz, 2H), 3.68 (br t, 2H), 3.47 (br t, 2H), 2.44 (br s,
7H), 2.32 (s, 3H); 13C NMR (100 MHz, CDCl3) δC 186.8, 165.5,
162.5, 145.5, 131.0, 130.7, 129.2, 54.6, 54.3, 45.8, 44.3, 41.9, 40.9, 21.8;
MS m/z 304 (M + H)+; IR νmax/cm−1 (KBr) 3351, 3000, 1669, 1642,
1504, 1475, 1276, 789; mp 97−98 °C. Anal. Calcd for C16H21N3O3: C,
63.35; H, 6.98; N, 13.85. Found: C, 63.67; H, 7.12; N, 14.12.
2-(4-Chlorophenyl)-N-(2-(4-methylpiperazin-1-yl)-2-oxoethyl)-2-
oxoacetamide (66). Starting material: 1,3-oxazol-2-oxime 150 mg
(0.47 mmol). The crude material was purified by column
chromatography (DCM/MeOH 97:3) to give the product as yellowish
solid (64 mg, 42% yield): 1H NMR (400 MHz, CDCl3) δH 8.23 (d, J =
8.4 Hz, 2H, AA′XX′), 7.98 (br s, NH), 7.41 (d, J = 8.4 Hz, 2H,
AA′XX′), 4.12 (d,, J = 4.0 Hz 2H), 3.63 (br t, 2H), 3.43 (br t, 2H),
2.40−2.37 (m, 4H), 2.28 (s, 3H); 13C NMR (100 MHz, CDCl3) δC
185.7, 165.3, 161.7, 141.0, 132.4, 131.5, 128.8, 54.7, 54.4, 46.0, 44.4,
42.0, 40.9; MS m/z 324 (M + H)+; IR νmax/cm−1 (KBr) 3344, 1673,
1645, 1586, 1443, 1273, 857; mp 127−128 °C. Anal. Calcd for
C15H18ClN3O3: C, 55.64; H, 5.60; N, 12.98. Found: C, 55.54; H, 5.42;
N, 12.78.
2-(4-Methoxyphenyl)-N-(2-morpholino-2-oxoethyl)-2-oxoaceta-
mide (60). Starting material: 1,3-oxazol-2-oxime 150 mg (0.49 mmol).
The crude material was purified by column chromatography (PE/
1
EtOAc 2:8) to give 70 mg of product as white solid (yield 46%). H
NMR (300 MHz, CDCl3) δH 8.33−8.8.30 (m, 2H, AA′XX′), 7.97 (br
s, NH), 6.94−6.91 (m, 2H, AA′XX′), 4.16 (br d, 2H), 3.87 (s, 3H),
3.71−3.65 (m, 6H), 3.46−43 (m, 2H); 13C NMR (75 MHz, CDCl3)
δC 185.3, 165.9, 164.8, 162.8, 133.8, 126.3, 114.0, 66.8, 66.4, 55.7, 45.0,
42.4, 41.0; MS m/z 307 (M + H)+; IR νmax/cm−1 (KBr) 3349, 3078,
1682, 1647, 1594, 1474, 1257, 861; mp 169−169.5 °C. Anal. Calcd for
C15H18N2O5: C, 58.82; H, 5.92; N, 9.15. Found: C, 58.93; H, 6.24; N,
9.36.
N-(2-Morpholino-2-oxoethyl)-2-oxo-2-(thiophene-2-yl)-
acetamide (61). Starting material: 1,3-oxazol-2-oxime 150 mg (0.54
mmol). The crude material was purified by column chromatography
(PE/EtOAc 2:8) to give 85 mg of product as white solid (yield 56%):
1H NMR (300 MHz, CDCl3) δH 8.36 (d, J = 4.0 Hz, 1H), 8.19 (br s,
NH), 7.80 (d, J = 4.8 Hz, 1H), 7.18−7.15 (m, 1H), 4.15 (d, J = 4.5 Hz,
2H), 3.71−3.66 (m, 6H), 3.53−3.42 (m, 2H); 13C NMR (75 MHz,
CDCl3) δC 177.6, 165.7, 161.0, 138.5, 138.0, 136.9, 128.4, 66.6, 66.40,
42.5, 41.1, 40.7; MS m/z 283 (M + H)+; IR νmax/cm−1 (KBr) 3371,
3071, 1691, 1658, 1495, 1359, 1275, 737; mp 193−194 °C. Anal.
Calcd for C12H14N2O4S: C, 51.05; H, 5.00; N, 9.92. Found: C, 51.34;
H, 5.36; N, 10.10.
N-(1-Morpholino-1-oxo-3-phenylpropan-2-yl)-2-oxo-2-phenyla-
cetamide (62). Starting material: 1,3-oxazol-2-oxime 150 mg (0.41
mmol). The crude material was purified by column chromatography
(PE/EtOAc 4:6) to give 76 mg of product as white solid (yield 50%).
Mixture of rotamers, signals are referred to the main rotamer: 1H
NMR (300 MHz, CDCl3) δH 8.21 (d, J = 8.2 Hz, 2H), 7.87 (br d,
NH), 7.64−7.59 (br t, 1H), 7.52−7.38 (br t, 2H), 7.34−7.23 (m, 5H),
5.18 (br q, 1H), 3.62−3.44 (m, 6H), 3.16−2.94 (m, 4H); 13C NMR
(75 MHz, CDCl3) δC 187.4, 169.0, 161.6, 135.8, 134.5, 131.0, 129.7,
129.6, 128.8, 128.6, 127.4, 66.4, 66.0, 49.7, 46.1, 42.4, 39.8; MS m/z
367 (M + H)+; IR νmax/cm−1 (KBr) 3277, 3027, 1665, 1642, 1524,
1486, 1211; mp 151.5−152 °C. Anal. Calcd for C21H22N2O4: C, 68.84;
H, 6.05; N, 7.65. Found: C, 68.95; H, 6.40; N, 7.34.
N-(2-Morpholino-2-oxoethyl)-2-oxo-2-p-tolylacetamide (67).
Starting material: 1,3-oxazol-2-oxime 150 mg (0.52 mmol). The
crude material was purified by column chromatography (DCM/
MeOH 97:3) to give the product as yellow solid (98 mg, 65% yield):
1H NMR (400 MHz, CDCl3) δH 8.20 (d, J = 8.2 Hz, 2H), 7.92 (br s,
NH), 7.28−7.25 (m, 2H) partially overlapped to the solvent, 4.17 (d, J
= 4.0 Hz, 2H), 3.71−3.67 (m, 6H), 3.47−3.46 (m, 2H), 2.42 (s, 3H);
13C NMR (100 MHz, CDCl3) δC 186.6, 165.8, 162.4, 145.6, 131.1,
130.7, 129.2, 66.6, 66.3, 44.9, 42.3, 40.8, 21.8; MS m/z 291 (M + H)+;
IR νmax/cm−1 (KBr) 3430, 3423, 1695, 1660, 1494, 1276, 785; mp 83−
84 °C. Anal. Calcd for C15H18N2O4: C, 62.06; H, 6.25; N, 9.65.
Found: C, 62.34; H, 6.43; N, 9.78.
2-Oxo-N-(1-oxo-3-phenyl-1-(pyrrolidin-1-yl)propan-2-yl)-2-p-tol-
ylacetamide (68). Starting material: 1,3-oxazol-2-oxime 150 mg (0.41
mmol). The crude material was purified by column chromatography
(n-hexane/AcOEt 7:3) to give the product as a light yellow solid (78
mg, 52% yield): 1H NMR (400 MHz, CDCl3) δH 8.12 (d, J = 8.0 Hz,
2H), 7.79 (br d, NH), 7.28−7.23 (m, 7H), 4.95 (br q, 1H), 3.47−3.30
(m, 3H), 3.09 (d, J = 7.4 Hz, 2H), 2.69−2.63 (m, 1H), 2.40 (s, 3H),
1.80−1.55 (m, 4H); 13C NMR (100 MHz, CDCl3) mixture of
rotamers: δC 186.8, 168.6, 161.7, 145.5, 136.1, 132.0, 131.1, 130.7,
129.5, 128.5, 127.1, 52.4, 46.3, 45.8, 39.5, 25.8, 23.9, 21.8; MS m/z 365
(M + H)+; IR νmax/cm−1 (KBr) 3239, 3062, 1680, 1662, 1624, 1454,
1228, 763; mp 88−89 °C. Anal. Calcd for C22H24N2O3: C, 72.51; H,
6.64; N, 7.69. Found: C, 72.52; H, 6.65; N, 7.65.
2-(3-Chlorophenyl)-N-(1-morpholino-1-oxo-3-phenylpropan-2-
yl)-2-oxoacetamide (63). Starting material: 1,3-oxazol-2-oxime 150
mg (0.38 mmol). The crude material was purified by column
chromatography (PE/EtOAc 5:5) to give 78 mg of product as white
1
solid (yield 52%): H NMR (300 MHz, CDCl3) δH 8.19 (d, J = 8.1
Hz, 2H), 7.93 (br d, NH), 7.42 (br d, 2H), 7.34−7.22 (m, 5H), 5.16
(br q, 1H), 3.64−3.58 (m, 2H), 3.55−3.25 (m, 4H), 3.14−2.87 (m,
G
dx.doi.org/10.1021/jo5005444 | J. Org. Chem. XXXX, XXX, XXX−XXX