Molecules 2018, 23, 321
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(Ar-C2,6), 43.46 (CH(CH3)2), 36.80 (Ar-NH-CO-CH2), 32.36 (NH-CO-CH2), 28.80 (CH2), 28.68 (CH2),
25.42 (CH2), 25.09 (CH2), 22.80 ((CH3)2); MS-ESI+: m/z 350 [M + H]+, 372 [M + Na]+.
[(8-Anilino-8-oxo-octanoyl)amino]N-benzylcarbamate (2b). Remained as a white solid (0.373 g, 94% yield);
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1H NMR (400 MHz, DMSO-d6):
δ
(ppm) = 11.36 (s, 1H, NH), 9.84 (s, 1H, NH), 8.22 (t, J = 5.8,
1H, NH-CH2), 7.60–7.56 (m, 2H, NH-Ar2,6-H), 7.36–7.22 (m, 7H, NH-Ar3,5-H, CH2-Ar2,3,4,5,6-H),
7.04–6.99 (m, 1H, NH-Ar4-H), 4.23 (d, 3J = 6.0, 2H, CH2-Ar), 2.28 (t, 3J = 7.4, 2H, Ar-NH-CO-CH2),
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2.07 (t, J = 7.9, 2H, NH-CO-CH2), 1.63–1.47 (m, 4H, (CH2)2), 1.36–1.24 (m, 4H, (CH2)2); 13C NMR
(100 MHz, DMSO-d6):
δ (ppm) = 171.63 (CO), 170.54 (CO), 155.79 (COO), 139.75 (Ar-C1),
139.49 (Ar-C1), 129.04 (CH2-Ar-C2,6), 128.72 (CH2-Ar-C3,5), 127.46 (NH-Ar-C3,5), 127.38 (CH2-Ar-C4),
123.32 (NH-Ar-C4), 119.43 (NH-Ar-C2,6), 44.49 (CH2-Ar), 36.78 (Ar-NH-CO-CH2), 32.35 (NH-CO-CH2),
28.81 (CH2), 28.67 (CH2), 25.41 (CH2), 25.09 (CH2); MS-ESI+: m/z 398 [M + H]+, 420 [M + Na]+.
[(8-Anilino-8-oxo-octanoyl)amino]N-ethylcarbamate (2c). Remained as a white powder (0.310 g, 92%
1
yield); H NMR (400 MHz, DMSO-d6):
δ (ppm) = 11.27 (s, 1H, NH), 9.84 (s, 1H, NH), 7.65–7.55
(m, 3H, NH, Ar2,6-H), 7.31–7.25 (m, 2H, Ar3,5-H), 7.04–6.99 (m, 1H, Ar4-H), 3.09–2.99 (m, 2H,
CH2-CH3), 2.29 (t, 3J = 7.3, 2H, Ar-NH-CO-CH2), 2.07 (t, 3J = 7.9, 2H, NH-CO-CH2), 1.62–1.46
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(m, 4H, (CH2)2), 1.35–1.24 (m, 4H, (CH2)2), 1.03 (t, J = 7.2, 3H, CH2-CH3); 13C NMR (100 MHz,
DMSO-d6):
δ (ppm) = 171.69 (CO), 170.42 (CO), 155.20 (COO), 139.82 (Ar-C1), 129.04 (Ar-C3,5),
123.33 (Ar-C4), 119.43 (Ar-C2,6), 36.76 (Ar-NH-CO-CH2), 35.90 (CH2-CH3), 32.35 (NH-CO-CH2),
28.79 (CH2), 28.67 (CH2), 25.42 (CH2), 25.12 (CH2), 14.26 (CH3); MS-ESI+: m/z 336 [M + H]+,
358 [M + Na]+.
[(8-Anilino-8-oxo-octanoyl)amino]N-phenylcarbamate (2d). Remained as a white solid (0.368 g, 96% yield);
1H NMR (400 MHz, DMSO-d6):
δ (ppm) = 11.54 (s, 1H, NH), 10.15 (s, 1H, NH), 9.82 (s, 1H, NH),
7.61–7.55 (m, 2H, Ar2,6-H), 7.48–7.43 (m, 2H, Ar20,60-H), 7.35–7.23 (m, 4H, Ar3,30,5,50-H) 7.08–6.98
(m, 2H, Ar4,40-H), 2.29 (t, 3J = 7.2, 2H, Ar-NH-CO-CH2), 2.14 (t, 3J = 7.2, 2H, NH-CO-CH2), 1.65–1.48
(m, 4H, (CH2)2), 1.39–1.24 (m, 4H, (CH2)2); 13C NMR (100 MHz, DMSO-d6):
δ (ppm) = 171.62 (CO),
170.69 (CO), 152.74 (COO), 139.77 (Ar-C1), 138.68 (Ar-C10), 129.35 (Ar-C3,5), 129.02 (CH2-Ar-C30,50),
123.50 (Ar-C4), 123.31 (Ar-C40), 119.48 (Ar-C2,6), 118.82 (Ar-C20,60), 36.81 (Ar-NH-CO-CH2),
32.82 (NH-CO-CH2), 28.82 (CH2), 28.57 (CH2), 25.41 (CH2), 25.08 (CH2); MS-ESI+: m/z 384 [M + H]+,
406 [M + Na]+.
[[2-(4-Pentoxyphenyl)acetyl]amino]N-isopropylcarbamate (
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). Remained as a white solid (0.272 g, 88%
1
3
yield); H NMR (400 MHz, DMSO-d6):
δ
(ppm) = 11.49 (s, 1H, NH), 7.60 (d, J = 3.16, 1H, NH),
7.17 (d, 3J = 3.7, 2H, Ar3,5-H), 6.85 (d, 3J = 4.2, 2H, Ar2,6-H), 3.93 (t, 3J = 6.3, 2H, CH2-O), 3.64–3.53
(m, 1H, CH(CH3)2), 1.73–1.63 (m, 2H, CH2), 1.48–1.37 (m, 2H, CH2), 1.08 (d, 3J = 3.7, 6H, C(CH3)2),
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0.93 (t, J = 7.4, 3H, CH2-CH3); remark: the two benzylic protons overlap with the signal of the
solvent, but could be identified and assigned in a two-dimensional NMR experiment; 13C NMR
(100 MHz, DMSO-d6):
δ (ppm) = 168.36 (CO), 157.90 (COO), 154.41 (Ar-C4), 130.46 (Ar-C3,5), 127.29
(Ar-C1), 114.61 (Ar-C2,6), 67.52 (CH2-O), 43.42 (CH(CH3)2), 38.34 (Ar-CH2), 31.21 (CH2), 22.81 (CH2),
19.16 (CH3), 14.08 (C(CH3)2); MS-ESI+: m/z 398.0 [M + H]+, 420.0 [M + Na]+.
tert-Butyl-piperazine-1carboxylate (3). A solution of 5 mmol di-tert-butyl dicarbonate in dichloromethane
(5 mL/mmol) was slowly added to a solution of piperazine (10 mmol) in dichloromethane
(25 mL/mmol). The batch was stirred over night before the solvent was removed under reduced
pressure. The addition of water led to precipitation of the raw product, which was filtrated and
extracted with dichloromethane. The combined organic phases were dried over sodium sulfate and
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evaporated to result in 0.616 g of white solid (66% yield). H NMR (400 MHz, CDCl3):
δ (ppm) = 3.40
(t, 3J = 5.0, 4H, N-(CH2)2), 2.82 (t, 3J = 5.2, 4H, HN-(CH2)2), 1.47 (s, 9H, C(CH3)3); 13C NMR (100 MHz,
CDCl3): δ (ppm) = 154.88 (CO), 79.41 (C(CH3)3), 45.88 (N-(CH2)2), 44.66 (N-(CH2)2), 28.38 (C(CH3)3).
tert-Butyl 4-(imidazole-1-carbonyl)piperazine-1-carboxylate
(4). Three-point-three millimoles
tert-butyl-piperazine-1carboxylate (3) were dissolved in dichloromethane (5 mL/mmol) and