ZHOU ET AL.
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(s, 3H, −SO2CH3), 1.85–2.02 (m, 4H, −CH2), 1.76–1.82 (m, 1H, −CH),
0.98–1.02 (m, 2H, −CH2), 0.76–0.80 (m, 2H, −CH2); 13C NMR
(100 MHz, CDCl3) δ: 171.9, 157.8, 146.1, 138.6, 131.9, 128.7,
127.9, 127.4, 116.5, 72.0, 44.7, 11.0, 7.3; MS (ESI): m/z calcd. for
Isopropyl 4-((5-(4-(methylsulfonyl)phenyl)pyridin-2-yl)oxy)-
piperidine-1-carboxylate (compound II-5)
Yield 54%. 1H NMR (400 MHz, CDCl3) δ: 8.39 (dd, J1 = 0.8 Hz,
J2 = 2.4 Hz, 1H, −ArH), 8.01 (d, J = 8.4 Hz, 2H, −ArH), 7.82 (dd,
J1 = 8.4 Hz, J2 = 2.4 Hz, 1H, −ArH), 7.71 (d, J = 8.4 Hz, 2H, −ArH), 6.84
(d, J1 = 0.8 Hz, J2 = 8.8 Hz, 1H, −ArH), 5.27–5.33 (m, 1H, −CH),
4.91–4.97 (m, 1H, −CH(CH3)2), 3.81 (br, 2H, −CH2), 3.33–3.39 (m,
2H, −CH2), 3.09 (s, 3H, −SO2CH3), 2.01–2.04 (m, 2H, −CH2), 1.76–1.79
(m, 2H, −CH2), 1.26 (d, J = 6.4 Hz, 6H, −CH(CH3)2); 13C NMR (100 MHz,
CDCl3) δ: 163.3, 155.3, 145.5, 143.5, 139.2, 137.6, 128.2, 128.0,
127.3, 112.0, 70.6, 68.6, 44.6, 41.1, 30.7, 22.3; MS (ESI): m/z calcd. for
C
22H26NO4S, [M+H]+ 400.1, found 400.4 [M+H]+. Anal. calcd. C,
66.14; H, 6.31; N, 3.51; S, 8.03, found: C, 66.01; H, 6.33; N, 3.53; S,
8.05.
Compounds I-5, II-3–11, III-4–5 were prepared in a manner similar
to that described for compound I-4.
Phenyl 4-((4ʹ-(methylsulfonyl)-[1,1ʹ-biphenyl]-4-yl)oxy)-
piperidine-1-carboxylate (compound I-5)
C
21H27N2O5S, [M+H]+ 419.1, found 419.7 [M+H]+. Anal. calcd. C,
Yield 44%. 1H NMR (400 MHz, CDCl3) δ: 7.99–8.00 (m, 1H, −ArH),
7.97–7.98 (m, 1H, −ArH), 7.74–7.75 (m, 1H, −ArH), 7.72–7.73 (m,
1H, −ArH), 7.58–7.59 (m, 1H, −ArH), 7.56–7.57 (m, 1H, −ArH),
7.35–7.40 (m, 2H, −ArH), 7.19–7.23 (m, 1H, −ArH), 7.11–7.14 (m,
2H, −ArH), 7.03–7.07 (m, 2H, −ArH), 4.63–4.68 (m, 1H, −CH),
3.63–3.90 (m, 4H, −CH2), 3.09 (s, 3H, −SO2CH3), 2.05 (br, 2H,
−CH2), 1.95 (br, 2H, −CH2); 13C NMR (100 MHz, CDCl3) δ: 157.8,
153.8, 151.4, 146.1, 146.1, 138.6, 132.0, 129.3, 129.3, 128.7,
127.9, 127.4, 125.3, 121.7, 116.6, 71.7, 44.7; MS (ESI): m/z calcd.
for C25H26NO5S, [M+H]+ 452.1, found 452.9 [M+H]+. Anal. calcd.
C, 66.50; H, 5.58; N, 3.10; S, 7.10, found: C, 66.72; H, 5.55; N, 3.11;
S, 7.11.
60.27; H, 6.26; N, 6.69; S, 7.66, found: C, 60.42; H, 6.25; N, 6.70; S,
7.67.
sec-Butyl 4-((5-(4-(methylsulfonyl)phenyl)pyridin-2-yl)oxy)-
piperidine-1-carboxylate (compound II-6)
Yield 67%. 1H NMR (400 MHz, CDCl3) δ: 8.39 (dd, J1 = 2.4 Hz,
J2 = 0.8 Hz, 1H, −ArH), 8.01 (d, J = 8 Hz, 2H, −ArH), 7.82 (dd,
J1 = 8.4 Hz, J2 = 2.4 Hz, 1H, −ArH), 7.71 (d, J = 8.4 Hz, 2H, −ArH),
6.84 (d, J1 = 8.8 Hz, J2 = 0.8 Hz, 1H, −ArH), 5.28–5.33 (m, 1H, −CH),
4.73–4.81 (m, 1H, −CH(CH3)CH2CH3), 3.81–3.86 (m, 2H, −CH2), 3.33–
3.40 (m, 2H, −CH2), 3.09 (s, 3H, −SO2CH3), 2.02 (br, 2H, −CH2), 1.77–
1.81 (m, 2H, −CH2), 1.50–1.68 (m, 2H, −CH(CH3)CH2CH3), 1.23 (d,
J = 6.0 Hz, 3H, −CH(CH3)CH2CH3), 0.92 (t, J = 7.6 Hz, 3H, −CH(CH3)
CH2CH3); 13C NMR (100 MHz, CDCl3) δ: 163.3, 155.4, 145.4, 143.5,
139.2, 137.6, 128.2, 128.0, 127.3, 112.0, 73.2, 70.6, 44.6, 41.1, 30.7,
29.1, 19.9, 9.7; MS (ESI): m/z calcd. for C22H29N2O5S, [M+H]+ 433.1,
found 433.8 [M+H]+. Anal. calcd. C, 61.09; H, 6.52; N, 6.48; S, 7.41,
found: C, 61.02; H, 6.54; N, 6.49; S, 7.43.
Methyl 4-((5-(4-(methylsulfonyl)phenyl)pyridin-2-yl)oxy)-
piperidine-1-carboxylate (compound II-3)
Yield 60%. 1H NMR (400 MHz, CDCl3) δ: 8.39 (d, J = 2.4 Hz, 1H,
−ArH), 8.01 (d, J = 8 Hz, 2H, −ArH), 7.82 (dd, J1 = 8.4 Hz, J2 = 2.4 Hz,
1H, −ArH), 7.71 (d, J = 8.4 Hz, 2H, −ArH), 6.84 (d, J = 8.4 Hz, 1H,
−ArH), 5.28–5.33 (m, 1H, −CH), 3.82 (br, 2H, −CH2), 3.72 (s, 3H,
−COOCH3), 3.36–3.43 (m, 2H, −CH2), 3.09 (s, 3H, −SO2CH3), 2.02–
2.04 (m, 2H, −CH2), 1.78–1.80 (m, 2H, −CH2); 13C NMR (100 MHz,
CDCl3) δ: 163.3, 156.0, 145.4, 143.4, 139.2, 137.6, 128.2, 128.1,
127.3, 112.0, 70.4, 52.6, 44.6, 41.2, 30.7; MS (ESI): m/z calcd. for
Phenyl 4-((5-(4-(methylsulfonyl)phenyl)pyridin-2-yl)oxy)-
piperidine-1-carboxylate (compound II-7)
Yield 49%. 1H NMR (400 MHz, CDCl3) δ: 8.40 (dd, J1 = 2.8 Hz,
J2 = 0.8 Hz, 1H, −ArH), 8.02 (d, J = 8 Hz, 2H, −ArH), 7.84 (dd,
J1 = 8.4 Hz, J2 = 2.4 Hz, 1H, −ArH), 7.72 (d, J = 8.4 Hz, 2H, −ArH),
7.34–7.40 (m, 2H, −ArH), 7.19–7.22 (m, 1H, −ArH), 7.11–7.14 (m, 2H,
−ArH), 6.87 (dd, J1 = 8.8 Hz, J2 = 0.8 Hz, 1H, −ArH), 5.35–5.41 (m, 1H,
−CH), 3.95 (d, J = 34 Hz, 2H, −CH2), 3.58 (d, J = 39.2 Hz, 2H, −CH2),
3.09 (s, 3H, −SO2CH3), 2.11 (br, 2H, −CH2), 1.90–1.93 (m, 2H, −CH2);
13C NMR (100 MHz, CDCl3) δ: 163.2, 153.8, 151.4, 145.5, 143.4,
139.3, 137.7, 129.3, 128.2, 127.4, 125.3, 121.7, 112.0, 100.0, 70.1,
44.6; MS (ESI): m/z calcd. for C24H25N2O5S, [M+H]+ 453.1, found
453.1 [M+H]+. Anal. calcd. C, 63.70; H, 5.35; N, 6.19; S, 7.09, found: C,
63.79; H, 5.37; N, 6.17; S, 7.10.
C
19H23N2O5S, [M+H]+ 391.1, found 391.6 [M+H]+. Anal. calcd. C,
58.45; H, 5.68; N, 7.17; S, 8.21, found: C, 58.57; H, 5.70; N, 7.14; S,
8.23.
Isobutyl 4-((5-(4-(methylsulfonyl)phenyl)pyridin-2-yl)oxy)-
piperidine-1-carboxylate (compound II-4)
Yield 54%. 1H NMR (400 MHz, CDCl3) δ: 8.39 (d, J = 2.4 Hz, 1H, −ArH),
8.01 (d, J = 8 Hz, 2H, −ArH), 7.82 (dd, J1 = 8.4 Hz, J2 = 2.4 Hz, 1H,
−ArH), 7.71 (d, J = 8.4 Hz, 2H, −ArH), 6.84 (d, J = 8.4 Hz, 1H, −ArH),
5.28–5.33 (m, 1H, −CH), 3.88 (d, J = 6.0 Hz, 2H, −CH2CH(CH3)2), 3.82–
3.85 (m, 2H, −CH2), 3.36–3.43 (m, 2H, −CH2), 3.09 (s, 3H, −SO2CH3),
2.01–2.04 (m, 2H, −CH2), 1.92–1.99 (m, 1H, −CH2CH(CH3)2), 1.75–
1.83 (m, 2H, −CH2), 0.95 (d, J = 6.4 Hz, 6H, −CH2CH(CH3)2); 13C NMR
(100 MHz, CDCl3) δ: 163.3, 155.7, 145.5, 143.5, 139.2, 137.6, 128.2,
128.1, 127.3, 112.0, 71.6, 70.5, 44.6, 41.2, 30.7, 29.7, 28.1, 19.1; MS
(ESI): m/z calcd. for C22H29N2O5S, [M+H]+ 433.1, found 433.5 [M+H]+.
Anal. calcd. C, 61.09; H, 6.52; N, 6.48; S, 7.41, found: C, 60.89; H, 6.55;
N, 6.47; S, 7.39.
Benzyl 4-((5-(4-(methylsulfonyl)phenyl)pyridin-2-yl)oxy)-
piperidine-1-carboxylate (compound II-8)
Yield 43%. 1H NMR (400 MHz, CDCl3) δ: 8.41 (d, J = 2.8 Hz, 1H, −ArH),
8.13 (d, J = 8.4 Hz, 2H, −ArH), 8.00 (dd, J = 8.4 Hz, 2H, −ArH), 7.73 (d,
J = 8.8 Hz, 2H, −ArH), 7.30–7.38 (m, 6H, −ArH), 5.15 (s, 2H, −OCH2Ph),
4.59–4.64 (m, 1H, −CH), 3.74–3.81 (m, 2H, −CH2), 3.48–3.54 (m, 2H,
−CH2), 3.09 (s, 3H, −SO2CH3), 1.99 (br, 2H, −CH2), 1.85 (br, 2H, −CH2);