Y. Li et al. / European Journal of Medicinal Chemistry 76 (2014) 182e192
189
88 ꢂC.1H NMR (300 MHz, DMSO-d6)
d
: 7.78(d, 1H, J ¼ 7.5 Hz, ArH),
HRMS (ESI) m/z (M þ H) calcd for C21H30N3O4S, 420.1957, found
7.41(s, 1H, ArH), 7.32(t, 1H, J ¼ 7.5 Hz, J ¼ 6.9 Hz, ArH), 7.20e7.16(m,
3H, ArH), 6.79(d, 2H, J ¼ 9.0 Hz, ArH), 5.90e5.77(m, 1H, ]CHe),
5.01(m, 2H, ]CH2), 4.34(s, 2H, eCH2eN), 4.17(q, 2H, J ¼ 7.2 Hz, e
CH2e), 1.54(s, 6H, eCH3 ꢁ 2), 1.18(t, 3H, J ¼ 7.2 Hz, eCH3). HRMS
(ESI) m/z (M þ H) calcd for C23H26N3O4S 440.1644, found 440.1645.
420.1951.
7.1.4.11. Ethyl 2-(4-(isopentyl(thiazol-2-yl)amino)phenoxy)-2-
methylpropanoate (14k). White solid, yield 86.6%, m.p.75e
76 ꢂC.1H NMR (300 MHz, DMSO-d6)
d
: 7.26(d, 1H, J ¼ 3.6 Hz, ArH),
7.17(d, 2H, J ¼ 8.7 Hz ArH), 6.98(d, 1H, J ¼ 3.6 Hz, ArH), 6.82(d, 2H,
J ¼ 8.7 Hz, ArH), 4.17(q, 2H, J ¼ 7.2 Hz, eCH2e), 3.65(t, 2H, J ¼ 7.5 Hz,
J ¼ 7.8 Hz, eCH2e), 1.55(s, 6H, eCH3 ꢁ 2), 1.53e1.30(m, 3H, eCH2e,
eCH<), 1.16(t, 3H, J ¼ 7.2 Hz, eCH3), 0.82(d, 6H, J ¼ 6.9 Hz, e
CH3 ꢁ 2). HRMS (ESI) m/z (M þ H) calcd for C21H30N3O4S 420.1957,
found 420.1963.
7.1.4.5. Ethyl 2-(4-(benzo[d]thiazol-2-yl(3-methylbut-2-enyl)amino)
phenoxy)-2-methylpropanoate (14e). Light brown solid, yield 25.5%,
m.p.97e98 ꢂC.1H NMR (300 MHz, DMSO-d6)
d: 7.79 (s, 1H, ArH),
7.35 (t, 2H, J ¼ 7.2 Hz, ArH), 7.20 (t, 1H, J ¼ 7.2 Hz, ArH), 7.16 (d, 2H,
J ¼ 8.7 Hz, ArH), 6.81 (d, 2H, J ¼ 8.7 Hz, ArH), 5.22 (t, 1H, J ¼ 7.2 Hz,
]C]CHeCH2e), 4.26 (d, 2H, J ¼ 7.2 Hz, ]CHeCH2e), 4.21 (q, 2H,
J ¼ 7.2 Hz, eCH2eCH3), 1.62 (s, 3H, eCH3), 1.53 (s, 6H, eCH3 ꢁ 2),
1.40 (s, 3H, eCH3), 1.20 (t, 3H, J ¼ 7.2 Hz, eCH2eCH3). HRMS (ESI) m/
z (M þ H) calcd for C25H30N3O4S 468.1957, found 468.1956.
7.1.4.12. Ethyl 2-(4-((2-ethoxyethyl)(thiazol-2-yl)amino)phenoxy)-2-
methylpropanoate (14l). White solid, yield 72.2%, m.p. 74e75 ꢂC.1H
NMR (300 MHz, DMSO-d6)
d
: 7.27 (d, 1H, J ¼ 3.6 Hz, ArH), 7.20 (d,
2H, J ¼ 8.7 Hz, ArH), 6.99 (d, 1H, J ¼ 3.6 Hz, ArH), 6.81 (d, 2H,
J ¼ 8.7 Hz, ArH), 4.21e4.14 (q, 2H, J ¼ 6.9 Hz, eCH2e), 3.79 (t, 2H,
J ¼ 6.0 Hz, eCH2e), 3.46 (t, 2H, J ¼ 6.0 Hz, eCH2e), 3.44e3.34 (q, 2H,
J ¼ 6.9 Hz, eCH2e), 1.54 (s, 6H, eCH3 ꢁ 2), 1.18 (t, 3H, J ¼ 6.9 Hz, e
CH3), 1.015 (t, 3H, J ¼ 6.9 Hz, eCH3). HRMS (ESI) m/z (M þ H) calcd
for C20H27N3O5S 422.1750, found 422.1749.
7.1.4.6. Ethyl 2-(4-(benzo[d]thiazol-2-yl(cyclopentylmethyl)amino)
phenoxy)-2-methylpropanoate (14f). White solid, yield 63.5%,
m.p.124e125 ꢂC.1H NMR (300 MHz, DMSO-d6)
d: 7.77(d, 1H,
J ¼ 7.5 Hz, ArH), 7.40(s, 1H, ArH), 7.32(t, 1H, J ¼ 7.8 Hz, J ¼ 7.5 Hz,
ArH), 7.22e7.15(m, 3H, ArH), 6.82(d, 2H, J ¼ 8.7 Hz, ArH), 4.18(q, 2H,
J ¼ 7.2 Hz, eCH2e), 3.58(d, 2H, J ¼ 6.9 Hz, eCH2e), 1.94(m, 1 H, e
CH<), 1.55(s, 6H, eCH3 ꢁ 2), 1.60e1.14 (m, 11H, eCH3, eCH2e ꢁ 4).
HRMS (ESI) m/z (M þ H) calcd for C26H32N3O4S 482.2114, found
482.2116.
7.1.4.13. Ethyl 2-(4-(allyl(thiazol-2-yl)amino)phenoxy)-2-
methylpropanoate (14m). Yellow solid, yield 59.6%, m.p.59e
60 ꢂC.1H NMR (300 MHz, DMSO-d6)
d
: 7.27(d, 1H, J ¼ 3.6 Hz, ArH),
7.17(d, 2H, J ¼ 8.7 Hz, ArH), 6.98(d, 1H, J ¼ 3.6 Hz, ArH), 6.79(d, 2H,
J ¼ 8.7 Hz, ArH), 5.90e5.77 (m, 1H, ]CHe), 5.09(m, 2H, ]CH2),
4.29(d, 2H, J ¼ 5.1 Hz, eCH2N), 4.17(q, 2H, J ¼ 7.2 Hz, eCH2e), 1.53(s,
6H, eCH3 ꢁ 2), 1.17(t, 3H, J ¼ 7.2 Hz, eCH3). 13C NMR (100 MHz,
7.1.4.7. Ethyl
phenoxy)-2-methylpropanoate (14g). White solid, yield 88.3%,
m.p.97e98 ꢂC.1H NMR (300 MHz, DMSO-d6)
2-(4-(benzo[d]thiazol-2-yl(cyclohexylmethyl)amino)
d
: 7.78(d,1H, J ¼ 7.5 Hz,
ArH), 7.43(s, 1H, ArH), 7.32(t, 1H, J ¼ 7.8 Hz, J ¼ 7.5 Hz, ArH), 7.21e
7.15(m, 3H, ArH), 6.82 (d, 2H, J ¼ 8.7 Hz, ArH), 4.18(q, 2H, J ¼ 7.2 Hz,
eCH2e), 3.58(d, 2H, J ¼ 6.9 Hz, eCH2e), 1.54(s, 6H, eCH3 ꢁ 2), 1.65e
0.91(m, 14H, eCH3, cyclohexyl). HRMS (ESI) m/z (M þ H) calcd for
CDCl3) d: 173.77, 160.06, 155.87, 152.69, 137.03, 132.98, 132.85,
129.47, 119.85,118.27, 112.71, 79.28, 61.59, 52.74, 25.35,14.06. HRMS
(ESI) m/z (M þ H) calcd for C19H24N3O4S 390.1488, found 390.1497.
C
27H34N3O4S 496.2270, found 496.2279.
7.1.4.14. Ethyl
amino)phenoxy)propanoate (14n). White solid, yield 29.8%,
m.p.81e82 ꢂC.1H NMR (300 MHz, DMSO-d6)
: 7.37 (d, 1H,
2-methyl-2-(4-((3-methylbut-2-enyl)(thiazol-2-yl)
7.1.4.8. Ethyl
phenoxy)-2-methylpropanoate (14h). White solid, yield 79.6%,
m.p.84e85 ꢂC.1H NMR (300 MHz, DMSO-d6)
7.77(d, 1H,
2-(4-(benzo[d]thiazol-2-yl(furan-2-ylmethyl)amino)
d
J ¼ 3.6 Hz, ArH), 7.15 (d, 2H, J ¼ 8.7 Hz, ArH), 6.98 (s, 1H, ArH), 6.81
(d, 2H, J ¼ 8.7 Hz, ArH), 5.19 (t, 1H, J ¼ 7.2 Hz, ]C]CHeCH2e), 4.24
(d, 2H, J ¼ 7.2 Hz, ]CHeCH2e), 4.20 (q, 2H, J ¼ 7.2 Hz, eCH2eCH3),
1.61 (s, 3H, eCH3), 1.54 (s, 6H, eCH3 ꢁ 2), 1.38 (s, 3H, eCH3), 1.19 (t,
d:
J ¼ 7.5 Hz, ArH), 7.40(s, 1H, ArH), 7.32(t, 1H, J ¼ 7.8 Hz, J ¼ 7.5 Hz,
ArH), 7.22e7.15(m, 3H, ArH), 6.82(d, 2H, J ¼ 8.7 Hz, ArH), 4.18(q,
2H, J ¼ 7.2 Hz, eCH2e), 3.58(d, 2H, J ¼ 6.9 Hz, eCH2e), 1.94(m, 1 H,
eCH<), 1.55(s, 6H, eCH3 ꢁ 2), 1.60e1.14 (m, 11H, eCH3, eCH2e
ꢁ 4). HRMS (ESI) m/z (M þ H) calcd for C25H26N3O5S 480.1593,
found 480.1589.
3H, J ¼ 7.2 Hz, eCH2eCH3). 13C NMR (100 MHz, CDCl3)
d: 173.75,
160.12, 155.69, 152.64, 137.00, 136.68, 132.88, 129.62, 119.77, 119.10,
112.51, 79.22, 61.50, 47.36, 25.57, 25.26, 17.48, 14.00. HRMS (ESI) m/z
(M þ H) calcd for C21H28N3O4S 418.1801, found 418.1801.
7.1.4.9. Ethyl
phenoxy)-2-methylpropanoate (14i). Light yellow solid, yield 93.9%,
m.p.91e92 ꢂC.1H NMR (300 MHz, DMSO-d6)
: 7.79 (d, 1H,
2-(4-((3-fluorobenzyl)(benzo[d]thiazol-2-yl)amino)
7.1.4.15. Ethyl
noxy)-2-methylpropanoate (14o). White solid, yield 65.4%,
m.p.119e120 ꢂC.1H NMR (300 MHz, DMSO-d6)
: 9.74(s, 1H, e
2-(4-((cyclopentylmethyl)(thiazol-2-yl)amino)phe-
d
d
J ¼ 6.6 Hz, ArH), 7.38e7.30 (m, 3H, ArH), 7.21e7.16 (m, 6H, ArH), 6.78
(d, 2H, J ¼ 9.0 Hz, ArH), 4.98 (s, 2H, eCH2e), 4.18 (q, 2H, J ¼ 7.2 Hz, e
CH2eCH3), 1.52 (s, 6H, eCH3 ꢁ 2), 1.21 (t, 3H, J ¼ 7.2 Hz, eCH2eCH3).
HRMS (ESI) m/z (M þ H) calcd for C27H26FN3O4S 508.1706, found
508.1716.
NHCOe), 7.26(d, 1H, J ¼ 3.6 Hz, ArH), 7.19(d, 2H, J ¼ 9.0 Hz ArH),
6.98(d, 1H, J ¼ 3.6 Hz, ArH), 6.82(d, 2H, J ¼ 9.0 Hz, ArH), 4.17(q, 2H,
J ¼ 7.2 Hz, eCH2e), 3.63(d, 2H, J ¼ 7.5 Hz, eCH2e), 1.92(m, 1H, e
CH<), 1.55(s, 6H, eCH3 ꢁ 2), 1.60e1.14(m, 11H, eCH3, eCH2e ꢁ 4,
cyclohexyl). HRMS (ESI) m/z (M þ H) calcd for C22H30N3O4S
432.1957, found 432.1960.
7.1.4.10. Ethyl 2-methyl-2-(4-(pentyl(thiazol-2-yl)amino)phenoxy)
propanoate (14j). White solid, yield 91.7%, m.p.81e82 ꢂC.1H
7.1.4.16. Ethyl
noxy)-2-methylpropanoate (14p). White solid, yield 87.2%,
m.p.104e105 ꢂC.1H NMR (300 MHz, DMSO-d6)
: 7.26(d, 1H,
J ¼ 3.6 Hz, ArH), 7.19(d, 2H, J ¼ 8.7 Hz, ArH), 6.98(d, 1H, J ¼ 3.6 Hz,
ArH), 6.82(d, 2H, J ¼ 8.7 Hz, ArH), 4.17(q, 2H, J ¼ 7.2 Hz, eCH2e),
3.53(d, 2H, J ¼ 7.2 Hz, eCH2eN), 1.55(m, 6H, eCH3 ꢁ 2), 1.16(t, 3H,
J ¼ 7.2 Hz, eCH3), 1.64e0.75(m, 11H). HRMS (ESI) m/z (M þ H) calcd
for C23H32N3O4S 446.2114, found 446.2110.
2-(4-((cyclohexylmethyl)(thiazol-2-yl)amino)phe-
NMR(CDCl3, 400 MHz)
d: 7.26e7.25(m, 1H, ArH), 7.13(d, 2H,
J ¼ 6.3 Hz, ArH), 6.90(d, 2H, J ¼ 6.3 Hz, ArH), 6.84e6.84(m, 1H, ArH),
4.27(q, 2H, J ¼ 5.4 Hz, eOCH2e), 3.68(t, 2H, J ¼ 5.7 Hz, eNCH2e),
1.66(s, 6H, 2 ꢁ eCH3), 1.54e1.52(m, 2H, eCH2e), 1.29e1.26(m, 7H,
2 ꢁ eCH2e, eCH3), 0.86(t, 3H, J ¼ 5.1 Hz, eCH3). 13C NMR (100 MHz,
d
CDCl3)
d: 173.81, 155.85, 152.77, 136.79, 132.93, 129.49, 120.00,
112.62, 79.31, 61.62, 49.98, 28.77, 27.76, 25.38, 22.37, 14.09, 13.96.