Med Chem Res
Benzyl 4-nicotinoylpiperazine-1-carboxylate (compound
N(CH2)2), 5.19 (s, 2H, O-CH2), 6.25–6.27 (m, 1H,
N-CHAr), 6.52–6.54 (m, 1H, N-CHAr), 6.93–6.94 (m, 1H,
Ar), 7.37–7.41 (m, 5H, Cbz), 10.11–10.14 (m, 1H, NH)
ppm.; 13C NMR (CDCl3, 100 MHz) d = 43.73 (CH2N),
43.78 (CH2N), 67.50 (OCH2), 109.55 (CHAr), 112.39
(CHAr), 121.56 (CHAr), 124.14 (CHAr), 128.09 (CHAr),
128.25 (CAr), 128.61 (CHAr), 136.41 (CAr), 155.22 (CO),
162.18 (CO) ppm.; IR (cm-1) m = 3255, 3104, 2905,
2851, 1695, 1593, 1545, 1473, 1446, 1421, 1358, 1281,
1245, 1232, 1191, 1131, 1100, 1014, 961, 849, 783, 742,
697, 680; MS (ESI) m/z (%) = 312 (M-H-); HRMS for
C17H18N3O3: calculated 312.1348, found 312.1342.
9f)
1
Yield, 98 %, yellow solid; H NMR (CDCl3, 400 MHz)
d = 3.44–3.76 (m, 8H, –N(CH2)2), 5.51 (s, 2H, O-CH2),
7.32–7.39 (m, 6H, Cbz, CHAr), 7.75–7.78 (m, 1H, CHAr),
8.66–8.68 (m, 2H, CHAr) ppm.; 13C NMR (CDCl3,
100 MHz) d = 42.14 (CH2N), 43.80 (CH2N), 47.53
(CH2N), 67.59 (CH2O), 123.65 (CHAr), 128.07 (CHAr),
128.28 (CHAr), 128.60 (CHAr), 131.18 (CHAr), 135.22
(CHAr), 136.22 (CAr), 147.84 (CHAr), 151.00 (CO), 155.07
(CAr), 167.96 (CO) ppm.; IR (cm-1) m = 3386, 3027, 2919,
2835, 2857, 1697, 1627, 1472, 1426, 1410, 1278, 1225,
1159, 1115, 1071, 1003, 980, 861, 830, 754, 746, 743, 698;
MS (ESI) m/z (%) = 326 (MH?); HRMS for C18H20N3O3:
calculated 326.1505, found 326.1499.
Benzyl 4-(1H-indole-2-carbonyl)piperazine-1-carboxylate
(compound 9d)
Yield, 92 %, white solid; 1H NMR (CDCl3, 400 MHz)
d = 3.66–3.68 (m, 4H, –N(CH2)2), 3.97 (s, 4H, –N(CH2)2),
5.21 (s, 2H, O-CH2), 6.79–6.80 (m, 1H, Ar), 7.17 (ddd,
J = 8.01, 7.01, 0.98 Hz, 1H, Ar), 7.32 (ddd, J = 8.24,
7.01, 1.14, 1H, Ar), 7.36–7.42 (m, 5H, Ar), 7.46 (dd,
J = 8.29, 0.90 Hz, 1H, Ar), 7.67 (dd, J = 8.03, 0.89 Hz,
1H, Ar), 9.68 (s, 1H, NH) ppm.; 13C NMR (CDCl3,
100 MHz) d = 43.73 (CH2N), 43.76 (CH2N), 43.79
(CH2N), 43.82 (CH2N), 67.59 (OCH2), 105.49 (CHAr),
111.87 (CHAr), 120.71 (CHAr), 121.94 (CHAr), 124.65
(CHAr), 127.37 (CHAr), 128.11 (CHAr), 128.29 (CHAr),
128.62 (CAr), 128.78 (CAr), 135.84 (CAr), 136.34 (CAr),
155.20 (CO), 162.81 (CO) ppm.; IR (cm-1) m = 3252,
3058, 2878, 1700, 1595, 1530, 1460, 1443, 1408, 1346,
1221, 1120, 804, 765, 745, 727, 693, 678; MS (ESI) m/
z (%) = 362 (M-H-); HRMS for C21H20N3O3: calculated
362.1505, found 362.1498.
Benzyl 4-((tert-butoxycarbonyl)-L-prolyl)piperazine-1-
carboxylate (compound 9g)
Yield, 99 %, white solid; 1H NMR (CDCl3, 400 MHz)
d = 1.41 (s, 4H, CH), 1.47 (s, 5H, CH), 1.82–1.91 (m, 2H,
CH2), 1.97–2.21 (m, 2H, CH2), 3.45–3.65 (m, 8H,
–N(CH2)2), 4.53–4.68 (m, 1H, CH), 5.17 (d, J = 3.64 Hz,
1H, NH), 5.32 (s, 2H, O-CH2), 7.35-7.39 (m, 5H, Cbz)
ppm.; 13C NMR (DMSO-d6, 100 MHz) d = 22.96 (CH2),
28.01 (CH3), 28.14 (CH3), 29.85 (CH2), 41.11 (CH2N),
43.34 (CH2N), 43.41 (CH2N), 44.12 (CH2N), 46.29 (CH2),
56.38 (CH), 56.22 (CH2N), 66.39 (CH2O), 78.15 (CO),
127.59 (CHAr), 127.88 (CHAr), 128.41 (CHAr), 136.71
(CHAr), 153.07 (CHAr), 153.25 (CHAr), 154.40 (CO),
170.22 (CO), 170.55 (CO) ppm.; IR (cm-1) m = 2979,
2954, 2866, 1704, 1680, 1658, 1450, 1404, 1364, 1246,
1210, 1156, 1114, 1074, 1044, 947, 928, 754, 698; MS
(ESI) m/z (%) = 418 (MH?); HRMS for C22H32N3O5:
calculated 418.2342, found 418.2353.
Benzyl 4-(1H-indole-3-carbonyl)piperazine-1-carboxylate
(compound 9e)
General procedure for synthesis of compounds 4c–g
Yield, 82 %, yellow-white solid; 1H NMR (DMSO-d6,
400 MHz) d = 3.38 (s, 1H, NCH2), 3.52–3.59 (m, 5H,
N(CH2)2), 3.73 (s, 2H, NCH2), 5.19 (s, 2H, –OCH2),
7.21–7.28 (m, 2H, Ar), 7.34–7.40 (m, 8H, Ar) ppm; 13C
NMR (DMSO-d6, 100 MHz) d = 43.41 (CH2N), 43.63
(CH2N), 44.50 (CH2N), 44.95 (CH2N), 66.93 (CH2O),
112.20 (CHAr), 120.48 (CHAr), 121.19 (CHAr), 122.24
(CHAr), 128.13 (CHAr), 128.30 (CHAr), 128.39 (CHAr),
128.92 (CHAr), 134.14 (CAr), 136.02 (CAr), 137.18 (CAr),
Compound 9c–g (0.55 mmol) was dissolved in the mixture
of EtOHabs (10 mL) and dry THF (10 mL), flushed with
argon, and degassed under reduced pressure. Ten percent
Pd/C (5 % m/m with respect to compound 9) was added,
and the reaction mixture was stirred under H2 atmosphere
for 3 h at room temperature. The catalyst was then filtered
off, and the solvent evaporated under reduced pressure.
The residue (0.55 mmol, 1.1 eq) was dissolved in dry
dichloromethane (15 mL). Compound 6 (0.50 mmol, 1 eq)
was added, and the mixture was stirred under argon for
20 min at room temperature. Na(OAc)3BH (0.23 g,
1.05 mmol, 2.1 eq) was added and 40 min of stirring at
room temperature followed. Dichloromethane was washed
154.85 (CAr), 161.56 (CO), 166.69 (CO) ppm.; IR (cm-1
)
m = 3513, 3032, 2916, 2863, 1696, 1425, 1357, 1281,
1230, 1199, 1119, 1069, 1002, 732, 697; MS (ESI) m/
z (%) = 362 (M-H-); HRMS for C21H20N3O3: calculated
362.1505, found 362.1507.
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