K.V. Sashidhara et al. / European Journal of Medicinal Chemistry 57 (2012) 302e310
309
J ¼ 9.0 Hz, 2H) 4.75e4.68 (m, 3H) 4.21 (q, J ¼ 7.1 Hz, 2H) 1.61 (d,
J ¼ 9.0 Hz, 2H) 4.47 (t, J ¼ 6.2 Hz, 1H) 4.18 (q, J ¼ 7.1 Hz, 2H) 3.84 (s,
2H) 1.99e1.90 (m, 2H) 1.22 (t, J ¼ 7.1 Hz, 3H) 1.04 (t, J ¼ 7.3 Hz, 3H);
J ¼ 6.7 Hz, 3H) 1.25 (t, J ¼ 7.1 Hz, 3H);13C NMR (CDCl3, 75 MHz)
d:
171.2, 166.0, 154.9, 154.8, 134.3, 130.8, 129.6, 127.8, 127.1, 126.9,
124.6, 121.9, 118.1, 115.7, 107.9, 73.0, 67.6, 61.4, 18.6, 14.2; ESIeMS:
(m/z): 394 (M þ H)þ.
13C NMR (CDCl3, 75 MHz)
d: 171.7, 165.9, 155.1, 133.8, 132.1, 131.7,
131.2, 129.2, 127.8, 127.3, 127.0, 126.6, 126.3, 126.1, 121.8, 115.7, 78.2,
61.2, 38.2, 26.2, 14.2, 9.7; ESIeMS: (m/z): 423 (M þ H)þ.
6.4.2. Ethyl 2-(4-(2-(naphthalen-2-yloxy)acetamido)phenoxy)
butanoate (9)
6.4.8. Ethyl 2-(4-(2-(2-sec-butylphenoxy)acetamido)phenoxy)
propanoate (18)
From 6c and ethyl 2-bromobutyrate; white solid, yield: 75%;
From 15c and ethyl 2-bromopropionate; yellow liquid, yield:
mp: 285e287 ꢁC; IR(KBr, cmꢂ1): 3502, 2940, 2282, 1727, 1680, 1528,
82%; IR(KBr, cmꢂ1): 3405, 2275, 1678, 1556, 1217, 1049; 1H NMR
1417, 1219, 1059, 762; 1H NMR (CDCl3, 300 MHz)
d
: 8.22 (s, NH)
(CDCl3, 300 MHz)
d
: 8.21 (s, NH) 7.47 (d, J ¼ 8.9 Hz, 2H) 7.26e7.16
7.83e7.74 (m, 3H) 7.50e7.39 (m, 4H) 7.37e7.21 (m, 2H) 6.88 (d,
J ¼ 8.9 Hz, 2H) 4.72 (s, 2H) 4.52 (t, J ¼ 6.2 Hz, 1H) 4.21 (q, J ¼ 7.1 Hz,
2H) 2.03e1.93 (m, 2H) 1.24 (t, J ¼ 7.1 Hz, 3H) 1.07 (t, J ¼ 7.3 Hz, 3H);
ESIeMS: (m/z): 408 (M þ H)þ.
(m, 2H) 7.06e7.01 (m, 1H) 6.89e6.84 (m, 3H) 4.72 (q, J ¼ 6.6 Hz,
1H) 4.59 (s, 1H) 4.25e4.18 (m, 2H) 3.19e3.08 (m, 1H) 1.61 (d,
J ¼ 6.7 Hz, 3H) 1.30e1.23 (m, 6H) 0.91 (t, J ¼ 7.3 Hz, 3H); 13C NMR
(CDCl3, 75 MHz) d:172.0,166.2,154.7,154.5,135.7,130.9,127.3,127.0,
122.5, 121.4, 115.7, 112.3, 73.0, 68.0, 61.2, 34.2, 30.0, 20.5, 18.5, 14.1,
6.4.3. Ethyl2-methyl-2-(4-(2-(naphthalen-2-yloxy)acetamido)
phenoxy)propanoate (10)
12.4; ESIeMS: (m/z): 400 (M þ H)þ.
From 6c and ethyl 2-bromo -2-methylpropionate; white solid,
6.4.9. Ethyl 2-(4-(2-(2-sec-butylphenoxy)acetamido)phenoxy)
butanoate (19)
yield: 80%; mp: 275e277 ꢁC; IR(KBr, cmꢂ1): 3401, 2940, 2285, 1718,
1645, 1566, 1504, 1217, 1059; 1H NMR (CDCl3, 300 MHz)
d
: 8.22 (s,
From 15c and ethyl 2-bromobutyrate; yellow liquid, yield: 80%;
NH) 7.83e7.74 (m, 3H) 7.50e7.37 (m, 4H) 7.26e7.21 (m, 2H) 6.86 (d,
J ¼ 8.8 Hz, 2H) 4.72 (s, 2H) 4.23 (q, J ¼ 7.1 Hz, 2H) 1.57 (s, 6H) 1.26 (t,
IR(KBr, cmꢂ1): 3415, 2275, 1688, 1556, 1217, 1039; 1H NMR (CDCl3,
300 MHz)
d
: 8.21 (s, NH) 7.46 (d, J ¼ 8.9 Hz, 2H) 7.26e7.16 (m, 2H)
J ¼ 7.0 Hz, 3H);13C NMR (CDCl3, 75 MHz)
d
: 174.1, 165.9, 154.8, 152.4,
7.06e7.01 (m,1H)6.90e6.84(m, 3H) 4.60(s, 2H)4.52(t, J ¼ 6.2 Hz,1H)
4.21 (q, J ¼ 7.1 Hz, 2H) 3.17e3.10 (m, 1H) 2.03e1.93 (m, 2H) 1.71e1.63
(m, 2H) 1.30e1.23 (m, 6H) 1.08 (t, J ¼ 7.3 Hz, 3H) 0.91 (t, J ¼ 7.3Hz, 3H);
134.2, 131.4, 130.0, 129.6, 127.7, 127.0, 126.8, 124.5, 121.3, 120.1, 118.0,
107.9, 79.5, 67.6, 61.4, 25.3, 14.1; ESIeMS: (m/z): 408 (M þ H)þ.
13C NMR (CDCl3, 75 MHz)
d: 171.6, 166.3, 155.2, 154.6, 135.9, 130.9,
6.4.4. Ethyl 2-(4-(2-(naphthalen-2-yloxy)acetamido)phenoxy)
acetate (11)
127.4, 127.1, 122.6, 121.6, 115.9, 112.4, 78.3, 68.1, 61.2, 34.3, 30.1, 26.2,
20.6, 14.3, 12.5, 9.7; ESIeMS: (m/z): 414 (M þ H)þ.
From 6c and ethyl bromoacetate; white solid, yield: 82%; mp:
255e257 ꢁC; IR(KBr, cmꢂ1): 3501, 2930, 2285, 1718, 1645, 1556,
6.4.10. Ethyl2-(4-(2-(2-sec-butylphenoxy)acetamido)phenoxy)-2-
methylpropanoate (20)
1504, 1227, 1019; 1H NMR (CDCl3, 300 MHz)
d: 8.23 (s, NH) 7.83e
7.74 (m, 3H) 7.53e7.37 (m, 3H) 7.26e7.21 (m, 3H) 6.90 (d,
J ¼ 8.9 Hz, 2H) 4.72 (s, 2H) 4.60 (s, 2H) 4.26 (q, J ¼ 7.0 Hz, 2H) 1.29 (t,
From 15c and ethyl 2-bromo -2-methylpropionate; yellow
liquid, yield: 86%; IR(KBr, cmꢂ1): 3405, 2272, 1678,1556, 1217, 1039;
J ¼ 7.1 Hz, 3H);13C NMR (CDCl3, 75 MHz)
d
: 168.9,166.0,155.0,154.9,
1H NMR (CDCl3, 300 MHz)
d
: 8.22 (s, NH) 7.44 (d, J ¼ 8.9 Hz, 2H)
134.3, 130.9, 130.1, 129.6, 127.7, 127.1, 126.9, 124.6, 122.0, 118.1, 115.2,
7.26e7.16 (m, 2H) 7.06e7.01 (m, 1H) 6.88e6.84 (m, 3H) 4.59 (s, 2H)
4.23 (q, J ¼ 7.1 Hz, 2H) 3.19e3.07 (m, 1H) 1.71e1.64 (m, 2H) 1.57 (s,
6H) 1.30e1.24 (m, 6H) 0.91 (t, J ¼ 7.3 Hz, 3H); 13C NMR (CDCl3,
107.9, 67.6, 65.8, 61.5, 14.2; ESIeMS: (m/z): 380 (M þ H)þ.
6.4.5. Ethyl 4-(4-(2-(naphthalen-2-yloxy)acetamido)phenoxy)
butanoate(12)
75 MHz) d: 174.2, 166.3, 154.6, 152.4, 135.8, 131.6, 127.4, 127.1, 122.6,
121.0, 120.3, 112.4, 79.6, 68.1, 61.5, 34.3, 30.1, 25.4, 20.6, 14.2, 12.5;
From 6c and ethyl 4-bromobutyrate; white solid, yield: 78%;
ESIeMS: (m/z): 414 (M þ H)þ.
mp: 272e274 ꢁC; IR(KBr, cmꢂ1): 3502, 2940, 2272, 1727, 1680, 1518,
1417, 1219, 1059, 762; 1H NMR (CDCl3, 300 MHz)
d
: 8.22 (s, NH)
6.4.11. Ethyl 4-(4-(2-(2-sec-butylphenoxy)acetamido)phenoxy)
butanoate (21)
7.83e7.74 (m, 3H) 7.50e7.37 (m, 4H) 7.27e7.21 (m, 2H) 6.87 (d,
J ¼ 8.9 Hz, 2H) 4.72 (s, 2H) 4.14 (q, J ¼ 7.0 Hz, 2H) 3.99 (t, J ¼ 6.0 Hz,
2H) 2.50 (t, J ¼ 7.2 Hz, 2H) 2.14e2.05 (m, 2H) 1.26 (t, J ¼ 7.1 Hz, 3H);
ESIeMS: (m/z): 408 (M þ H)þ.
From 15c and ethyl 4-bromobutyrate; yellow liquid, yield: 86%;
mp: 215e217 ꢁC; IR(KBr, cmꢂ1): 3409, 2283, 1689, 1524, 1219, 1049,
726; 1HNMR(CDCl3, 300 MHz)
d:8.22(s, NH)7.49e7.46 (m, 2H) 7.28e
7.18 (m, 2H) 7.08e7.03 (m, 1H) 6.91e6.87 (m, 3H) 4.62 (s, 2H) 4.17 (q,
J ¼ 7.1 Hz, 2H) 4.02 (t, J ¼ 6.1 Hz, 2H) 3.20e3.10 (m, 1H) 2.53 (t,
J ¼ 6.3 Hz, 2H) 2.17e2.08 (m, 2H) 1.74e1.66 (m, 2H) 1.33e1.25 (m, 6H)
6.4.6. Ethyl 2-(4-(2-(naphthalen-2-ylthio)acetamido)phenoxy)
propanoate (13)
From 7c and ethyl 2-bromopropionate; white solid, yield: 80%;
0.93 (t, J ¼ 7.3 Hz, 3H); 13C NMR (CDCl3, 75 MHz)
d: 173.2,166.3,156.1,
154.7, 135.9, 130.2, 127.4, 127.1, 122.6, 121.7, 115.0, 112.4, 68.1, 67.1, 60.5,
mp: 292e294 ꢁC; IR(KBr, cmꢂ1): 3511, 2910, 2285, 1718, 1556, 1504,
1227,1019; 1HNMR(CDCl3, 300MHz)
d:8.52(s,NH)7.79e7.72 (m, 4H)
34.3, 30.9, 30.1, 24.7, 20.6, 14.3, 12.5; ESIeMS: (m/z): 414 (M þ H)þ.
7.48e7.39(m, 3H)7.34(d, J¼ 9.0Hz,2H)6.80(d, J¼ 8.9Hz,2H)4.67(q,
J ¼ 6.8 Hz,1H) 4.18 (q, J ¼ 8.9 Hz, 2H) 3.84(s, 2H) 1.58 (d, J ¼ 6.7 Hz, 3H)
6.4.12. Ethyl 2-(4-(2-(2-chlorophenoxy)acetamido)phenoxy)
propanoate (22)
1.22 (t, J ¼ 7.1 Hz, 3H);13C NMR (CDCl3, 75 MHz)
d: 172.1, 165.9, 154.8,
133.8, 132.1, 131.7, 131.3, 129.2, 127.8, 127.3, 127.0, 126.6, 126.3, 126.2,
From 16c and ethyl 2-bromopropionate; white solid, yield: 85%;
121.8, 115.7, 73.1, 61.4, 38.2, 18.6, 14.2; ESIeMS: (m/z): 410 (M þ H)þ.
mp: 215e217 ꢁC; IR(KBr, cmꢂ1): 3315, 3013, 2275, 1678, 1556, 1504,
1327, 1019; 1H NMR (CDCl3, 300 MHz)
d: 8.58 (s, NH) 7.55e7.52 (m,
6.4.7. Ethyl 2-(4-(2-(naphthalen-2-ylthio)acetamido)phenoxy)
butanoate (14)
2H) 7.46e7.43 (m, 1H) 7.32e7.26 (m, 1H) 7.06e6.96 (m, 2H) 6.90 (d,
J ¼ 9.0 Hz, 2H) 4.74 (q, J ¼ 6.8 Hz, 1H) 4.66 (s, 2H) 4.23 (q, J ¼ 7.1 Hz,
2H) 1.62 (d, J ¼ 6.7 Hz, 2H) 1.27 (t, J ¼ 7.3 Hz, 3H);13C NMR (CDCl3,
From 7c and ethyl 2-bromo -2-methylpropionate; white solid,
yield: 82%; mp: 295e297 ꢁC; IR(KBr, cmꢂ1): 3305, 3013, 2275, 1718,
75 MHz) d: 172.2,165.5, 154.8, 152.7,130.9, 130.5, 128.3, 123.2, 123.0,
1556, 1504, 1327, 1019; 1H NMR (CDCl3, 300 MHz)
d
: 8.52 (s, NH)
121.6, 115.8, 114.3, 73.1, 68.3, 61.4, 18.6, 14.2; ESIeMS: (m/z): 378
7.79e7.72 (m, 4H) 7.48e7.39 (m, 3H) 7.33 (d, J ¼ 8.9 Hz, 2H) 6.81 (d,
(M þ H)þ.