776 Journal of Medicinal Chemistry, 2011, Vol. 54, No. 3
Yermolina et al.
(q, J =7.3 Hz, 4 H), 1.02 (t, J = 7.3 Hz, 6 H). 13C NMR (100
MHz, CDCl3) δ 172.6, 170.1, 162.0, 138, 129.5 (2 C), 128.6 (2 C),
100.2, 96.5, 57.5, 49.0 (2 C), 35.0, 12.5 (2 C). HRMS-ESI calcd
for C16H21IN3O2 [M þ H]þ 414.06730; found 414.06654.
N-((3-(4-Bromophenyl)isoxazol-5-yl)methyl)-2-(diethylamino)-
2-(Diethylamino)-N-((3-(4-methylphenyl)isoxazol-5-yl)methyl)-
ethanamide (8q). Yield 50%; yellow oil; Rf 0.17 (EtOAc); tR
-
HPLC: 1.43 min (100%). IR (film) υmax 3330 (br), 2962, 1674,
1612, 1516, 1432, 1254, 1168, 1026 cm-1. 1H NMR (500 MHz,
CDCl3) δ 8.15 (br s, 1H), 7.66 (d, J = 7.9 Hz, 2H), 7.24 (d, J =
7.9 Hz, 2H), 6.48 (s, 1H), 4.61 (br s, 1H), 4.11 (q, J = 7.2 Hz,
4H), 2.39 (s, 3H), 1.25 (t, J = 7.2 Hz, 6H). 13C NMR (125 MHz,
CDCl3) δ 172.3, 169.3, 162.3, 161.3, 137.4 (2 C), 129.2, 128.9
(2 C), 127.6, 102.1, 57.4, 49.04 (2 C), 34.9, 12.4 (2 C). HRMS-EI
calcd for C17H24N3O2 [M þ H]þ 302.3914; found 302.3926.
N-((3-(3-Iodo-4-methoxyphenyl)isoxazol-5-yl)methyl)-2-(diethyl-
amino)ethanamide (8r). Yield 62%; colorless oil; Rf 0.22
(EtOAc); tR - HPLC: 1.43 min (99.6%). IR film υmax 3324
ethanamide (8k). Yield 64%; yellow oil; Rf 0.11 (EtOAc); tR
-
HPLC: 1.47 min (98.2%). IR (film) υmax 3307 (br), 2966, 2923,
1
1670, 1508, 1427, 1275, 1072, 830 cm-1. H NMR (500 MHz,
CDCl3) δ 8.04 (s, 1 H), 7.64 (d, J = 8.4 Hz, 2 H), 7.58 (d, J =
8.4 Hz, 2 H), 6.47 (s, 1 H), 4.63 (d, J = 6.1 Hz, 2 H), 4.29 (s, 2 H),
3.16 (s, 2 H), 2.61 (q, J = 6.9 Hz, 4 H), 0.88 (t, J = 6.9 Hz, 6 H).
13C NMR (125 MHz, CDCl3) δ 172.5, 170.0, 161.8, 136.3, 129.5
(2 C), 128.3 (2 C), 127.6, 100.3, 57.4, 49.0 (2 C), 35.0, 12.5 (2 C).
HRMS-ESI calcd for C16H21BrN3O2 [M þ H]þ 366.08117;
found 366.08056.
(br), 2960, 2928, 1668, 1605, 1516, 1426, 1262, 1134, 1071 cm-1
.
1H NMR (400 MHz, CDCl3) δ 8.20 (d, J = 2.1 Hz, 1 H), 7.99
(s, 1 H), 7.73 (dd, J = 2.0, 8.4 Hz, 1 H), 6.86 (d, J = 8.5 Hz, 1 H),
6.45 (s, 1 H), 4.61 (d, J = 6.2 Hz, 2 H), 3.93 (s, 3 H), 3.11 (s, 2 H),
2.57 (q, J = 7.1 Hz, 4 H), 1.03 (t, J = 7.1 Hz, 6 H). 13C NMR
(100 MHz, CDCl3) δ 172.6, 169.7, 161.1, 159.6, 138.0, 128.3,
119.5, 111.0, 100.1, 86.4, 57.5, 56.7, 49.0 (2 C), 35.0, 12.5 (2 C).
HRMS-EI calcd for C17H23IN3O3 [M þ H]þ 444.0784; found
444.0789.
N-(3-(4-Chlorophenyl)isoxazol-5-yl)methyl)-2-(diethylamino)-
ethanamide (8l). Yield 42%; white solid; mp 81-83 ꢀC; Rf 0.11
(EtOAc); tR - HPLC: 1.46 min (97.1%). FTIR (KBr pellet)
υmax 3286 (br), 2969, 1659, 1521, 1424, 1090, 1028, 847,
1
805 cm-1. H NMR (500 MHz, CDCl3) δ 8.01 (s, 1 H), (d,
J = 8.4 Hz, 2 H), (d, J = 8.4 Hz, 2 H), 6.47 (s, 2 H), 4.63 (d, J =
6.2 Hz, 2 H), 3.10 (s, 2 H), 2.57 (q, J = 7.1 Hz, 4 H), 1.03 (t, J =
7.1 Hz, 6 H). 13C NMR (125 MHz, CDCl3) δ 172.6, 170.0, 161.8,
136.3, 129.4 (2 C), 128.3 (2 C), 127.6, 100.3, 57.5, 49.0 (2 C), 35.0,
12.5 (2 C). HRMS-ESI calcd for C16H21ClN3O2 [M þ H]þ
322.13168; found 322.13131.
2-(Diethylamino)-N-((3-(2-furyl)isoxazol-5-yl)methyl)ethanamide
(8m). Yield 56%; colorless oil; Rf 0.16 (EtOAc); tR - HPLC:
1.46 min (96.8%). IR (film) υmax 3342 (br), 2966 (br), 2928, 1669,
1517, 1455, 1334, 1259, 1207, 1049 (br) cm-1. 1H NMR (500 MHz,
CDCl3) δ 8.08 (br s, 1 H), 7.54 (dd, J = 0.6, 1.2 Hz, 1 H), 6.87 (dd,
J = 0.5, 2.8 Hz, 1 H), 6.51 (dd, J = 1.6, 1.8 Hz, 1 H), 6.43 (s, 1 H),
4.61(d,J=6.2Hz,2H),3.15(s,2H),2.62(d,J= 7.1 Hz, 4 H), 1.05
(t, J = 7.1 Hz, 6 H). 13C NMR (125 MHz, CDCl3) δ 169.4, 155.1,
144.1, 111.9, 110.6, 99.9, 57.01, 49.0 (2 C), 34.9, 29.9, 28.8, 12.3 (2 C).
HRMS-EI calcd for C14H20N3O3 [M þ H]þ 278.3269; found
278.3265.
2-(Diethylamino)-N-((1-(4-iodophenyl)-1H-1,2,3-triazol-4-yl)-
methyl)ethanamide (15b). Yield 90%; white solid; mp 127-129 ꢀC;
Rf 0.19 (MeOH/EtOAc, 1%); tR - HPLC: 5.3 min (MeOH,
97.2%). FTIR (KBr pellet) υmax 3291, 3152, 3054, 2967, 2932,
1
2805, 1654, 1525, 1498, 1348, 1224, 1045 cm-1. H NMR (400
MHz, CDCl3) δ 8.02 (br s, 1 H), 7.97 (s, 1 H), 7.81 (d, J = 8.7 Hz, 2
H), 7.47 (d, J = 8.7 Hz, 2 H), 4.58 (d, J = 6.1 Hz, 2 H), 3.04
(s, 2 H), 2.52 (q, J = 7.1 Hz, 4 H), 0.96 (t, J = 7.1 Hz, 6 H). 13
C
NMR (100 MHz, CDCl3) δ 172.6, 146.1, 139.0 (2 C), 136.7, 122.1
(2 C), 120.3, 93.7, 57.5, 48.8 (2 C), 34.5, 12.3 (2 C). HRMS-EI calcd
for C15H21IN5O [M þ H]þ 414.2646; found 414.2648
N-((1-(4-Chlorophenyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(diethyl-
amino)ethanamide (15c). Yield 55%; white solid; mp 100 ꢀC;
Rf 0.61 (EtOAc/hexanes, 1:3); tR - HPLC: 1.47 min (97.6%).
FTIR (KBr pellet) υmax 3286 (br), 2972, 1660, 1521, 1424, 1090,
1028 cm-1. 1H NMR (400 MHz, CDCl3) δ 8.02 (br s, 1 H), 7.96
(s, 1 H), 7.66 (d, J = 8.8 Hz, 1 H), 7.49 (d, J = 8.8 Hz, 2 H), 4.59
(d, J = 6.2 Hz, 2 H), 3.04 (s, 1 H), 2.52 (q, J = 7.1 Hz, 4 H), 0.99
(t, J = 7.1 Hz, 6 H). 13C NMR (100 MHz, CDCl3) δ 172.8,
146.2, 135.7, 134.8, 130.1 (2 C), 121.8 (2 C), 120.6, 57.6, 48.9
(2 C), 34.5, 12.4 (2 C). HRMS-EI calcd for C15H21ClN5O [M þ
H]þ 322.1435; found 322.1437.
2-(Diethylamino)-N-((3-(pentafluorophenyl)isoxazol-5-yl)methyl)-
ethanamide (8n). Yield 68%: white solid; mp 100-102 ꢀC; Rf
0.39 (EtOAc); tR - HPLC: 1.42 min (100%). FTIR (KBr pellet)
υ
max 3316, 2973, 2939, 2877, 2823, 1670, 1508, 1423, 1388, 1361,
1211, 1079, 995, 817 cm-1. 1H NMR (400 MHz, CDCl3) δ 8.02
(br s, 1 H), 6.51 (s, 1 H), 4.70 (d, J = 6.2 Hz, 2H), 3.11 (s, 2 H),
2.58 (q, J = 7.0 Hz, 4 H), 1.04 (t, J = 7.0 Hz, 6 H). 13C NMR (100
MHz, CDCl3) δ 172.4, 170.2, 161.0, 151.7, 145.8, 143.8, 139.0,
137.0, 103.6, 103.1, 57.2, 48.8 (2 C), 34.7, 12.2 (2 C). HRMS-EI
calcd for C16H17F5N3O3 [M þ H]þ 378.3171; found 378.3176.
2-(Diethylamino)-N-((3-propylisoxazol-5-yl)methyl)ethanamide
(8o). Yield 46%; colorless oil; Rf 0.11 (EtOAc); tR - HPLC:
1.47 min (100%). IR (film) υmax 3324 (br), 2965, 2933, 1674, 1605,
N-((1-(4-Bromophenyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(diethyl-
amino)ethanamide (15d). Yield 86%; yellow solid; mp 116-118 ꢀC;
Rf 0.17 (EtOAc); tR - HPLC: 1.45 min (100%). FTIR (KBr pellet)
υ
max 3288 (br), 3056, 2970, 2817, 1663, 1500, 1349, 1265, 1045 cm-1
.
1H NMR (500 MHz, CDCl3) δ 8.03 (br s, 1 H), 7.97 (s, 1 H), 7.62
(m, 4H), 4.59(d, J=6.1Hz, 2H), 3.04(s, 3H), 2.52(q, J=7.1Hz,
4 H), 0.98 (t, J = 7.1 Hz, 6 H). 13C NMR (125 MHz, CDCl3) δ
172.7, 146.2, 136.1, 133.1 (2 C), 122.6, 122.0 (2 C), 120.5, 57.6, 48.9
(2 C), 34.5, 12.4 (2 C). HRMS-EI calcd for C15H21BrN5O [M þ
H]þ 367.2641; found 367.2643.
1
1516, 1426, 1262, 1206, 1134, 1074, 809 cm-1. H NMR (500
MHz, CDCl 3) δ 7.82 (br s, 1 H), 6.00 (s, 1 H), 4.55 (d, J = 6.2 Hz,
1 H), 3.10 (s, 2 H), 2.61 (t, J = 7.5 Hz, 2 H), 2.57 (q, J = 7.1 Hz,
4 H), 1.67 (s, 2 H), 1.03 (t, J=7.1Hz, 6H), 0.97(t, J=7.4Hz, 3H),
1.05 (t, J = 7.1 Hz, 6 H). 13C NMR (125 MHz, CDCl3) δ 168.7,
164.3, 125.5, 101.8, 57.4, 49.0 (2 C), 35.0, 28.2, 21.8, 13.9, 12.4
(2 C). HRMS-EI calcd for C13H24N3O2 [M þ H]þ 254.3486;
found 254.3489.
2-(Diethylamino)-N-((1-heptyl-1H-1,2,3-triazol-4-yl)methyl)-
ethanamide (15e). Yield 59%; white solid; mp 120 ꢀC; Rf 0.10
(EtOAc); tR - HPLC: 1.47 min (98.8%). FTIR (KBr pellet)
υ
max 3297, 1646, 1544, 1420, 1264, 1221, 1026 cm-1. 1H NMR
(400 MHz, CDCl3) δ 7.95 (br s, 1 H), 7.51 (s, 1 H), 4.53-4.56 (m,
1 H), 4.31-4.33 (m, 1 H), 3.04 (s, 2H), 2.55 (q, J = 7.1 Hz, 4 H),
1.88 (m, 2H), 1.33 (m, 9H), 0.99 (t, J = 7.1 Hz, 6 H), 0.87 (t, J =
5.1 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 172.6, 145.1, 122.1,
57.6, 50.6, 48.9 (2 C), 34.6, 31.8, 29.9, 28.8, 26.6, 22.7, 14.2, 12.5
(2 C). HRMS-EI calcd for C16H32N5O [M þ H]þ 310.2610;
found 310.2604.
2-(Diethylamino)-N-((1-phenyl-1H-1,2,3-triazol-4-yl)methyl)-
ethanamide (15f). Yield 50%; white solid; mp 92 ꢀC; Rf 0.29
(MeOH/EtOAc, 1%); tR - HPLC: 1.47 min (99.7%). FTIR
(KBr pellet) υmax 3288 (br), 3153, 3056, 2970, 2933, 2871, 2817,
1663, 1524, 1500, 1349, 1265, 1224 cm-1. 1H NMR (500 MHz,
2-(Diethylamino)-N-((3-(2,6-dimethylphenyl)isoxazol-5-yl)-
methyl)ethanamide (8p). Yield 69%; colorless oil; Rf 0.12
(EtOAc); tR - HPLC: 1.44 min (96.1%). IR (film) υmax 3319
(br), 2969 (br), 2932, 2871, 2823, 1676, 1601, 1513, 1456, 1423,
1388, 1355, 1207, 1162 cm-1 1H NMR (400 MHz, CDCl3)
.
δ 8.00 (br s, 1 H), 7.20 (t, J = 7.9 Hz, 1 H), 7.08 (d, J = 7.9 Hz,
2 H), 6.09 (s, 1 H), 4.66 (d, J = 6.3 Hz, 2 H), 3.08 (s, 2 H), 2.54
(q, J = 7.1 Hz, 4 H), 2.12 (d, J = 2.7 Hz, 6 H), 1.01 (t, J =
7.1 Hz, 6 H). 13C NMR (100 MHz, CDCl3) δ 172.4, 169.3, 162.3,
137.4 (2 C), 129.2, 128.9 (2 C), 127.6, 103.1 (2 C), 57.4, 49.04
(2 C), 34.9, 20.4, 12.4 (2 C). HRMS-EI calcd for C18H26N3O2
[M þ H]þ 316.2019; found 316.2010