All melting points were recoded using “Electrothermal Capillary apparatus” and all were uncorrected. IR spectra were determined as KBr pellets, values are characterized in cm− 1. Mass spectral data were recoded using electron impact ionization technique at 70 eV. “1H NMR (500 MHz) and 13C NMR” (100 MHz) bands were achieved on “Jeol ECA 500 MHz spectrometer” and chemical shifts were presented as ppm. “Elemental microanalyses were done on Microanalytical Units in Cairo University and the National Research Centre”. All final compounds exhibited purity above 95% as detected by HPLC. Analysis was carried out using Agilent 1100 series apparatus. Detection method was using diode array (DAD) ultraviolet (UV) detector was used at 254 nm. Column used was C18 column Zorbax ODS (4.6 x 150 mm i.d.,5 mm) and eluent was water: acetonitrile (30:70), flow rate = 1 mL/min, temperature 25°C.
4.1.3. Synthesis of 2-(2-((1-carbamoylcycloalkyl)(aralkyl)amino)-2-oxoethyl)-N-alkyl/aralkylhydrazine-1-carboxamides 5a-d, 6a-d and 7a-d
A 0.01 mol of the suitable isocyante was added to 0.01 mol of hydrazine 4a-c in dichloroethane and the mixture was for 3 h. The mixture was filtered off and the residue was washed with diethyl ether to get 5a-d, 6a-d and 7a-d.
4.1.3.1. 2-(2-((1-Carbamoylcyclopentyl)(phenyl)amino)-2-oxoethyl)-N-propylhydrazine-1-carboxamide (5a)
Yield 84%, “1HNMR” (CDCl3d6, δ, ppm): 0.93 (t, 3H, J = 7.5 Hz, CH3-CH2), 1.46–1.50 (m, 2H, CH2-CH3), 1.60–1.67 (m, 4H, 2CH2-cyclopentyl), 1.90–1.93 (m, 2H, CH2-cyclopentyl), 2.46–2.51 (m, 2H, CH2-cyclopentyl), 3.72 (s, 2H, CH2-CH2-CH3), 3.82–3.86 (m, 2H, CH2-NH), 5.91 (br.s, 1H, NH), 7.14–7.16 (m, 2H, Har.), 7.28–7.45 (m, 3H, Har.), 7.95 (s, 2H, NH2). 13CNMR (CDCl3d6, δ, ppm): 11.38 (CH3), 22.75 ( CH2-CH3),, 23.20, 34.18 (CH2-cyclopentyl), 42.17 (CH2-CH2-CH3), 55.33 (CH2-CO) 63.22 (Cq), 128.76, 129.48, 130.14, 137.06 (aromatic carbons), 157.54, 166.98, 170.65 (3C = O), IR (KBr, cm− 1) 3240, 3120, 3096, 2950 (3NH, NH2), 1701, 1664, 1604 (3C = O). MS (EI) m/z (%): 361.45 (M+, 10%), Anal. calcd. for C18H27N5O3: C, 59.81; H, 7.53; N, 19.39. Found: C, 59.50; H, 7.33; N, 19.50.
4.1.3.2. 2-(2-((1-Carbamoylcyclopentyl)(phenyl)amino)-2-oxoethyl)-N-isopropylhydrazine-1-carboxamide (5b)
Yellowish brown oil, yield 88%,; “1HNMR” (CDCl3d6, δ, ppm): 1.07 (d, 3H, J = 6.5 Hz, CH3-CH), 1.11–1.15 (m, 2H, CH2-cyclopentyl), 1.52–1.97 (m, 2H, 2CH2-cyclopentyl), 2.33–2.42 (m, 2H, CH2-cyclopentyl), 3.82 (s, 2H, CH2-NH), 4.38 (s, 1H, (CH3)2), 5.60 (br.s, 1H, NH), 7.02–7.14 (m, 2H, Har.), 7.23 (s, 2H, NH2), 7.40–7.44 (m, 3H, Har.). 13CNMR (CDCl3d6, δ, ppm): 23.30 (2CH3), 25.37, 37.22 (CH2-cyclopentyl), 41.63 (CH-CH3), 45.0 (CH2-NH), 70.8 (Cq), 128.70, 129.39, 129.51, 137.59 (aromatic carbons), 165.97, 170.08, 171.67 (3C = O), IR (KBr, cm− 1) 3321, 3232, 3086, 2974 (3NH, NH2), 1755, 1664, 1604 (3C = O), MS (EI) m/z (%): 361.45 (M+, 10%), Anal. calcd. for C18H27N5O3: C, 59.81; H, 7.53; N, 19.38. Found: C, 59.50; H, 7.32; N, 19.50.
4.1.3.3. N-Butyl-2-(2-((1-carbamoylcyclopentyl)(phenyl)amino)-2-oxoethyl)hydrazine-1-carboxamide (5c)
Yield 89%, “1HNMR” (CDCl3d6, δ, ppm): 0.83(t, 3H, J = 7.65 Hz, CH3), 1.22–1.46 (m, 8H, 4CH2-cyclopentyl), 1.62–2.05 (m, 4H, (CH2)2-CH3), 2.99 (t, 2H, J = 6.7 Hz, CH2-(CH2)2-CH3), 3.40 (s, 2H,CH2-CO), 4.29 (br.s, 1H, NH), 7.01–7.15 (m, 2H, Har.), 7.10 (s, 2H, NH2), 7.11–7.40 (m, 5H, Har.), 8.29 (br.s, 1H, NH). 13CNMR (CDCl3d6, δ, ppm): 13.82 (CH3-CH2), 20.09 (CH3-CH2), 24.81, 25.00 (2CH2-cyclopentyl), 32.06 (CH3-CH2-CH2), 40.50 ( CH2-(CH2)2-CH3), 55.08 (CH2-CO), 67.91 (Cq), 115.23, 116.56, 129.26, 129.37 (aromatic carbons), 158.89, 175.99, 192.75 (3C = O); IR (KBr, cm− 1) 3369, 3300, 3226, 2956 (3NH, NH2), 1703, 1691, 1640 (3C = O); MS (EI) m/z (%): 375.47 (M+, 10%), Anal. calcd. for C19H29N5O3: C, 60.78; H, 7.79; N, 18.65. Found: C, 60.75; H, 7.77; N, 18.62.
4.1.3.4. N-Benzyl-2-(2-((1-carbamoylcyclopentyl)(phenyl)amino)-2-oxoethyl)hydrazine-1-carboxamide (5d)
Pale yellow oil, yield 89%, “1HNMR” (CDCl3d6, δ, ppm): 1.40–1.71 (m, 8H, CH2-cyclopentyl), 2.13–2.16 (m, 3H, CH2-cyclohexyl), 4.42 (s, 2H, CH2-CO), 4.46 (br.s, 1H, NH), 7.05 (br.s, 1H, NH), 7.12 (br.s, 1H, NH), 7.24 (s, 2H, NH2), 7.26–7.36 (m, 7H, Har.), 7.39–7.42 (m, 3H, Har.). 13CNMR (CDCl3d6, δ, ppm): 22.71, 25.4, 32.41 (2CH2-cyclopentyl), 44.23 (CH2-C6H5), 57.4 (CH2-CO), 68.51 (Cq), 119.72, 121.9, 122.7, 126.8, 127.5, 128.4, 134.59, 136.31 (aromatic carbons), 157.78, 164.7, 178.0 (3C = O), IR (KBr, cm− 1) 3369, 3288, 3030, 2937 (3NH, NH2), 1703, 1691, 1650 (3C = O);MS (EI) m/z (%): 409.21 (M+, 18%), Anal. calcd. for C22H27N5O3: C, 64.53; H, 6.65; N, 17.10. Found: C, 64.50; H, 6.68; N, 17.15.
4.1.3.5. 2-(2-((1-Carbamoylcyclohexyl)(phenyl)amino)-2-oxoethyl)- N - propyl hydrazine − 1 -carboxamide (6a): White solid, m.p. 200°C, yield 85%, “1HNMR” (CDCl3d6, δ, ppm): 0.83 (t, 3H, J = 8 Hz, CH3), 1.38–1.81 (m, 12H, 5CH2-cyclohexyl, 2H, CH2-CH3), 2.99 (t, 2H, J = 8 Hz, CH2-CH2-CH3), 3.37 (s, 2H, CH2-CO), 4.31 (br.s, 1H, NH), 7.14 (s, 2H, NH2), 7.41–7.45 (m, 10H, Har.), 8.364.31 (br.s, 1H, NH).. 13CNMR (CDCl3d6, δ, ppm): 11.76 (CH3), 21.08 ( CH2-CH3), 22.70, 23.68, 33.97 (3CH2-cyclohexyl), 41.50 (CH2-CH2-CH3), 55.54 (CH2-CO), 62.45 (Cq), 127.93, 129.09, 130.51, 137.45 (aromatic carbons), 157.85, 166.58, 168.76 (3C = O), IR (KBr, cm− 1) 3371, 3300, 3068, 2960 (3NH, NH2), 1720, 1687, 1678 (3C = O); MS (EI) m/z (%): 375.47 (M+, 22%). Anal. calcd. for C19H29N5O3: C, 60.78; H, 7.79; N, 18.65. Found: C, 60.75; H, 7.76; N, 18.62.
4.1.3.6. 2-(2-((1-Carbamoylcyclohexyl)(phenyl)amino)-2-oxoethyl)-N-isopropylhydrazine-1-carboxamide (6b)
Yellowish white oil, yield 86%, “1HNMR” (CDCl3d6, δ, ppm): 1.20 (d, 3H, J = 6.5 Hz, CH3), 1.84 (s, 4H, 2CH2-cyclohexyl), 1.96 (s, 6H, 3CH2-cyclohexyl), 3.64 (s, 2H, CH2-CO), 3.96–4.03 (m, 1H, CH-CH3)2), 4.39 (br.s, 1H, NH), 7.29 (s, 2H, NH2), 7.39–7.48 (m, 5H, Har.), 13CNMR(CDCl3d6, δ, ppm): 22.90 (CH3), 23.26, 24.51, 30.91 (3CH2-cyclopentyl), 41.63 (CH-(CH3)2), 51.93 (CH2-CO), 64.32 (Cq), 129.73, 129.99, 130.02, 137.02 (aromatic carbons), 163.94, 166.73, 175.60 (3C = O), IR (KBr, cm− 1) 3365, 3320, 3055, 2981 (3NH, NH2), 1728, 1690, 1676 (3C = O);MS (EI) m/z (%): 375.47 (M+, 15%), Anal. calcd. for C19H29N5O3: C, 60.78; H, 7.79; N, 18.65. Found: C, 60.78; H, 7.81; N, 18.67.
4.1.3.7. N-Butyl-2-(2-((1-carbamoylcyclohexyl)(phenyl)amino)-2-oxoethyl)hydrazine-1-carboxamide (6c)
Yield 87%, “1HNMR” (CDCl3d6, δ, ppm): 0.86 (t, 3H, J = 4 Hz, CH3), 1.27–1.40 (m, 10H, 5CH2-cyclohexyl), 1.48–1.81 (m, 4H, (CH2)2-CH3), 3.01 (t, 2H, J = 8 Hz, CH2-(CH2)2-CH3), 3.35 (s, 2H,CH2-CO), 4.29 (br.s, 1H, NH), 7.03–7.16 (m, 2H, Har.), 7.27 (s, 2H, NH2), 7.40–7.48 (m, 3H, Har.), 8.26 (br.s, 1H, NH). 13CNMR (CDCl3d6, δ, ppm): 13.73 (CH3-CH2), 20.08 (CH3-CH2), 22.72, 24.43, 32.06 (3CH2-cyclohexyl), 34.17 (CH3-CH2-CH2), 42.89 ( CH2-(CH2)2-CH3), 58.28 (CH2-CO), 63.22 (Cq), 129.42, 130.16, 137.12, 149.12 (aromatic carbons), 157.67, 167.19, 170.49 (3C = O), IR (KBr, cm− 1) 3369, 3300, 3226, 2956 (3NH, NH2), 1703, 1691, 1619 (3C = O); MS (EI) m/z (%): 389.59 (M+, 15%), Anal. calcd. for C19H29N5O3: C, 60.78; H, 7.79; N, 18.65. Found: C, 60.75; H, 7.76; N, 18.62.
4.1.3.8. N-Benzyl-2-(2-((1-carbamoylcyclohexyl)(phenyl)amino)-2-oxoethyl)hydrazine-1-carboxamide (6d)
White solid, m.p. 210–212°C, 84.5%, “1HNMR”(CDCl3d6, δ, ppm): 1.40–1.55 (m, 5H, CH2-cyclohexyl), 1.72–1.82 (m, 2H, CH2-cyclohexyl), 2.13–2.16 (m, 3H, CH2-cyclohexyl), 4.40 (s, 2H, CH2-CO), 4.48 (br.s, 1H, NH), 7.09 (br.s, 1H, NH), 7.11 (br.s, 1H, NH), 7.24 (s, 2H, NH2), 7.26–7.34 (m, 7H, Har.), 7.39–7.45 (m, 3H, Har.). 13CNMR (CDCl3d6, δ, ppm): 22.71, 25.4, 32.41 (3CH2-cyclohexyl), 44.23 (CH2-C6H5), 57.4 (CH2-CO), 68.55 (Cq), 119.70, 121.7, 122.7, 126.6, 127.6, 128.3, 134.59, 136.31 (aromatic carbons), 156.79, 164.7, 178.0 (3C = O), IR (KBr, cm− 1) 3369, 3288, 3030, 2937 (3NH, NH2), 1703, 1691, 1625 (3C = O);MS (EI) m/z (%): 423.52 (M+, 5%), Anal. calcd. for C23H29N5O3: C, 65.23; H, 6.90; N, 16.54. Found: C, 65.25; H, 6.93; N, 16.55.
4.1.3.9. 2-(2-((1-Carbamoylcyclohexyl)(p-tolyl)amino)-2-oxoethyl)-N-propylhydrazine-1-carboxamide (7a)
Pale yellow oil, 87%, “1HNMR” (CDCl3d6, δ, ppm): 0.95 (t, 3H, J = 4 Hz, CH3-CH2), 1.64–1.79 (m, 10H, 5CH2-cyclohexyl), 1.80 (s, 3H, CH3), 1.93–1.96 (m, 2H, CH2-CH2-CH3), 2.32 (s, 3H, CH3), 2.70 (br.s, 1H, NH), 3.73 (br.s, 1H, NH), 3.84 (t, 3H, J = 8, CH2-CH2-CH3), 4.38 ( s, 2H, CH2-CO), 2.70 (s, 1H, NH), 7.22 (d, 2H, J = 4 Hz, Har.), 7.24 (d, 2H, J = 4 Hz, Har.), 7.28 (s, 2H, NH2). 13CNMR (CDCl3d6, δ, ppm): 11.19 (CH3-CH2), 22.45, 23.34, 37.21 (3CH2, cyclohexyl), 23.41 (CH2-CH3), 44.43 (CH2-CH2-CH3), 53.94 (CH2-CO), 70.83 (Cq), 129.08, 129.22, 137.58, 140.49 (aromatic carbons), 149.06, 166.00, 171.69 (3C = O), IR (KBr, cm− 1) 3290, 3215, 3057, 2960 (3NH, NH2), 1720, 1662, 1602 (3C = O); MS (EI) m/z (%): 389.50 (M+, 10%), Anal. calcd. for C20H31N5O3: C, 61.67; H, 8.02; N, 17.98. Found: C, 61.65; H, 8.05; N, 17.97.
4.1.3.10. 2-(2-((1-Carbamoylcyclohexyl)(p-tolyl)amino)-2-oxoethyl)-Nisopropylhydrazine-1-carboxamide (7b)
Pale yellow oil, 90%, “1HNMR” (CDCl3d6, δ, ppm): 1.08–1.13 (m, 4H, 2CH2-cyclohexyl), 1.15 (d, 2H, J = 8 Hz, CH3-CH), 1.17–1.27 (m, 6H, 3CH2-cyclohexyl), 1.83 ( s, 3H, CH3), 2.77 (br.s, 1H, NH), 3.75 (s, 2H, CH2-CO), 4.40 (s, 1H, CH-CH3)2), 4.67 (br.s, 1H, NH), 6.70 (br.s, 1H, NH),, 7.15 (d, 2H, J = 8 Hz, Har.), 7.25 (d, 2H, J = 8 Hz, Har.), 7.28 (s, 2H, NH2). 13CNMR (CDCl3d6, δ, ppm): 23.77 (CH3), 23.97 (CH-(CH3)2), 24.21, 29.69, 37.22 (3CH2-cyclohexyl), 54.15 (CH2-CO), 70.84 (Cq), 129.20, 129.39, 129.46, 137.60 (aromatic carbons), 165.96, 170.08, 178.78 (3C = O), IR (KBr, cm− 1) 3313, 3234, 3084, 2972 (3NH, NH2), 1750, 1689, 1656 (3C = O); MS (EI) m/z (%): 389.50 (M+, 15%), Anal. calcd. for C20H31N5O3: C, 61.67; H, 8.02; N, 17.98. Found: C, 61.65; H, 8.03; N, 17.95.
4.1.3.11. N-Butyl-2-(2-((1-carbamoylcyclohexyl)(p-tolyl)amino)-2-oxoethyl)hydrazine-1-carboxamide (7c)
Pale yellow, 89%, “1HNMR” (CDCl3d6, δ, ppm): 0.87 (t, 3H, J = 7.5 Hz, CH3-CH2), 1.15 (t, 4H, J = 7 Hz, CH2, CH2-CH3), 1.95–1.1.98 (m, 10H, 5CH2-cyclohexyl), 3.62 (s, 2H,CH2-CO), 3.79 ( t, 2H, J = 7.5 Hz, CH2-CH2-CH2-CH3) ,4.31 (br.s, 1H, NH), 7.07 (d, 2H, J = 5.8 Hz, Har.), 7.16 (d, 2H, J = 5.8 Hz, Har.), 7.20 (s, 2H, NH2), 7.98 (br.s, 1H, NH), 8.91 (br.s, 1H, NH), 13CNMR (CDCl3d6, δ, ppm): 13.7 (CH3-CH2), 18.2 (CH3-CH2), 20.8 (CH3), 22.4, 25.3 (2CH2-cyclohexyl), 31.8 (CH2-cyclohexyl), 36.81 (CH3-CH2-CH2), 42.8 ( CH2-(CH2)2-CH3), 58.2 (CH2-CO), 71.0 (Cq), 129.0, 129.2, 137.5, 140.4 (aromatic carbons), 159.1, 166.7, 180.2 (3C = O), IR (KBr, cm− 1) 3330, 3214, 3050, 2937 (3NH, NH2), 1730, 1688, 1672 (3C = O); MS (EI) m/z (%): 403.53 (M+, 7%), Anal. calcd. for C21H33N5O3: C, 62.51; H, 8.24; N, 17.36. Found: C, 62.54; H, 8.25; N, 17.35.
4.1.3.12. N-Benzyl-2-(2-((1-carbamoylcyclohexyl)(p-tolyl)amino)-2-oxoethyl)hydrazine-1-carboxamide (7d)
Oil, 85%, “1HNMR” (CDCl3d6, δ, ppm): 1.68-2.00 (m, 10H, 5CH2-cyclohexyl), 2.34 (s, 3H, CH3), 4.28 (s, 2H, CH2-CO), 5.23 (s, 2H, CH2-C6H5), 7.10 (s, 1H, NH), 7.22–7.29 (m, 9H, Har.), 8.99 (br.s, 1H, NH). 13CNMR (CDCl3d6, δ, ppm): 21.02 (CH3), 22.21, 24.25, 30.21 (3CH2-cyclohexyl), 43.86 (CH2-C6H5), 52.43 (CH2-CO), 70.55 (Cq), 127.15, 127.34, 128.49, 129.69, 129.91 131.21, 134.21, 137.52 (aromatic carbons), 158.21, 166.82, 180.10 (3C = O), IR (KBr, cm− 1) 3332, 3294, 3215, 2935 (3NH, NH2), 1715, 1693, 1662 (3C = O); MS (EI) m/z (%): 437.54 (M+, 30%), Anal. calcd. for C24H31N5O3: C, 65.88; H, 7.14; N, 16.01. Found: C, 65.89; H, 7.15; N, 16.03.
4.1.4. Synthesis of substituted (2,4,5-trioxoimidazolidin-1-yl)amino)-N-phenylacetamido)cycloalkane-1-carboxamides 8a-d, 9a-d and 10a-d
To a 0.001 mol of 5a-d, 6a-d or 7a-d in dry benzene a 0.002 mol of oxalyl chloride was supplemented. The mix was heated for 3 h then benzene was allowed to evaporate. The residual substance was subjected to column chromatography using mixture of CHCl2 and CH3OH as mobile phase to obtain 8a-d, 9a-d and 10a-d.
4.1.4.1. 1-(N- Phenyl-2-((2,4,5 - trioxo-3-propyl imidazolidin-1-yl)amino)acetamido) cyclopentane-1-carboxamide (8a)
White solid, m.p. 110–112°C, yield 80%, HPLC: purity 98.7%, Rt = 3.98 min. “1HNMR” (CDCl3d6, δ, ppm): 0.91–1.01 (m, 3H, CH3-CH2), 1.61–1.91 (m, 10H, 4CH2-cyclopentyl, CH2-CH3), 3.63 (t, 2H, J = 8, CH2-CH2-CH3), 3.73 (s, 2H, CH2-CO), 4.59 (br.s, 1H, NH), 7.22 (s, 2H, NH2), 7.38–7.54 (m, 5H, Har.). 13CNMR (CDCl3d6, δ, ppm): 11.13 (CH3), 20.94 (CH2-CH3), 23.92, 36.14 (2CH2-cyclopentyl), 41.67 (CH2-CH2-CH3), 44.47 (CH2-CO), 71.09 (Cq), 115.56, 128.35, 130.10, 135.70 (aromatic carbons), 149.09, 152.55, 154.54 (3C = O, imidazolidine), 166.5, 169.30 (2C = O); IR (KBr, cm− 1) 3365, 3251 (NH, NH2), 1762, 1755, 1689, 1631, 1591 (5C = O);MS (EI) m/z (%): 415.45 (M+, 4%), Anal. calcd. for C20H25N5O5: C, 57.82; H, 6.07; N, 16.86. Found: C, 57.81; H, 6.15; N, 16.75.
4.1.4.2. 1-(2-((3 – Isopropyl − 2,4,5-trioxo imidazolidin-1-yl)amino) – N -phenylacetamido)cyclopentane-1-carboxamide (8b)
Yellowish brown oil, yield 75%, HPLC: purity 99.4%, Rt = 4.30 min. “1HNMR” (CDCl3d6, δ, ppm): 1.07–1.11 (m, 2H, CH2-cyclopentyl), 1.14 (d, 6H, J = 6.5, (CH3)2), 1.22–1.26 (m, 2H, CH2-cyclopentyl), 1.39–1.50 (m, 4H, 2CH2-cyclopentyl) 2.07 (br.s, 1H, NH), 3.71 (s, 2H, CH2-CO), 4.51 (m, 1H, CH-(CH3)2), 7.26 (s, 2H, NH2), 7.36–7.45 (m, 5H, Har.). 13C NMR (CDCl3, δ, ppm): 20.43 (CH3), 23.00, 37.00 (2CH2-cyclopentyl), 42.47 (CH2-CO), 51.16 (CH-(CH3)2), 63.85 (Cq), 129.65, 129.77, 130.12, 137.57 (aromatic carbons), 148.78, 151.81, 159.06 (3C = O, imidazolidine), 165.06, 177.20 (2C = O), IR (KBr, cm− 1) 3304, 3234, 3207 (NH, NH2), 1755, 1747, 1662, 1610, 1593 (5C = O); MS (EI) m/z (%): 415.45 (M+, 25%), Anal. calcd. for C20H25N5O5: C, 57.82; H, 6.07; N, 16.86. Found: C, 57.72; H, 6.15; N, 16.69.
4.1.4.3. 1-(2-((3-Butyl-2,4,5-trioxoimidazolidin-1-yl)amino)-N-phenylacetamido)cyclopentane-1-carboxamide (8c)
Yellowish brown oil, yield 80%, HPLC: purity 96.5%, Rt = 3.39 min. “1HNMR” (CDCl3d6, δ, ppm): 0.87 (t, 3H, J = 8 Hz, CH3), 1.13–1.18 (m, 2H, CH3-CH2), 1.23–1.27 (m, 2H, CH2-CH2-CH3), 1.29–1.68 (m, 8H, 4CH2-cyclopentyl), 3.50 (s, 2H, CH2-CO), 3.80 (t, 2H, J = 8 Hz, CH2-CH2-CH2-CH3), 4.50 (br.s, 1H, NH), 7.22 ( br.s, 2H, NH2), 7.27–7.38 (m, 5H, Har.). 13CNMR (CDCl3d6, δ, ppm): 13.70 (CH3), 18.18 (CH2-CH3), 24.14, 36.64 (2CH2-cyclopentyl), 29.38 (CH2-CH2- CH3), 42.88 (CH2-CH2- CH2-CH3), 52.98 (CH2-CO), 72.38 (Cq), 119.31, 128.65, 129.02 (3CHar.), 137.38 (Car.), 148.45, 155.07, 159.22 (3C = O, imidazolidine), 163.07, 177.28 (2C = O). IR (KBr, cm− 1) 3336, 3253, 3244 (NH, NH2), 1766, 1747, 1734, 1716, 1687 (5C = O); MS (EI) m/z (%): 429.48 (M+, 20%), Anal. calcd. for C21H27N5O5: C, 58.73; H, 6.34; N, 16.31. Found: C, 58.80; H, 6.31; N, 16.35.
4.1.4.4. 1-(2- ((3 -Benzyl- 2,4,5- trioxo imidazolidin-1-yl) amino)- N- phenylacetamido) cyclopentane-1-carboxamide (8d)
Pale yellow viscous oil, yield 71%, HPLC: purity 98%, Rt = 7.18 min. “1HNMR” (CDCl3d6, δ, ppm): 1.14–1.27 (m, 4H, 2CH2-cyclopentyl), 1.94–2.08 (m, 4H, 2CH2-cyclopentyl), 4.71 (s, 2H, CH2-C6H5), 4. 76 (br.s, 1H, NH), 7.14 (s, 2H, NH2), 7.16–7.29 (m, 10H, Har.), 13CNMR (CDCl3d6, δ, ppm): 25.01, 35.55 (2CH2-cyclopentyl), 42.93 (CH2-C6H5), 43.95 (CH2-CO), 67.90 (Cq), 128.96, 128.98, 129.01 129.07, 129.08, 129.12, 136.90, 137.25 (aromatic carbons), 148.56, 151.68, 153.43 (3C = O, imidazolidine), 166.92, 172.75 (2C = O). IR (KBr, cm− 1) 34195, 3273, 3186, 3089 (NH, NH2), 1759, 1720, 1680, 1665, 1631 (5C = O); MS (EI) m/z (%): 463.39 (M+, 10%), Anal. calcd. for C24H25N5O5: C, 62.19; H, 5.44; N, 15.11. Found: C, 62.21; H, 5.45; N, 15.15.
4.1.4.5. 1-(N- Phenyl-2-((2,4,5 - trioxo- 3-propyl imidazolidin-1-yl)amino) acetamido) cyclohexane-1-carboxamide (9a)
White solid, m.p. 120°C, yield 75%, HPLC: purity 97.6%, Rt = 5.05 min. “1HNMR” (CDCl3d6, δ, ppm): 1.10–1.23 (m, 3H, CH3-CH2), 1.41–1.91 (m, 12H, 5CH2-cyclohexyl, CH2-CH3), 3.61 (t, 2H, J = 8, CH2-CH2-CH3), 3.75 (s, 2H, CH2-CO), 4.59 (br.s, 1H, NH), 7.22 (s, 2H, NH2), 7.38–7.54 (m, 5H, Har.). 13CNMR (CDCl3d6, δ, ppm): 11.14 (CH3), 20.84 (CH2-CH3), 23.92, 36.14 (2CH2-cyclopentyl), 41.61 (CH2-CH2-CH3), 44.47 (CH2-CO), 69.12 (Cq), 115.56, 128.35, 130.10 (3CHar.), 135.91 (Car.), 149.09, 152.55, 154.54 (3C = O, imidazolidine), 166.2, 169.30 (2C = O), IR (KBr, cm− 1) 3313, 3294, 3142 (NH, NH2), 1745, 1690, 1685, 1666, 1630 (5C = O); MS (EI) m/z (%): 429.48 (M+, 25%), Anal. calcd. for C21H27N5O5: C, 58.73; H, 6.34; N, 16.31. Found: C, 58.71; H, 6.38; N, 16.29.
4.1.4.6. 1-(2- ((3-Isopropyl − 2,4,5 – trioxo imidazolidin-1-yl) amino) -N-phenyl acetamido) cyclohexane-1-carboxamide (9b)
White solid, m.p. 160°C, yield 80%, HPLC: purity 99.4%, Rt = 4.27 min. “1HNMR” (CDCl3d6, δ, ppm): 1.11 (d, 6H, J = 4 Hz, (CH3)2), 1.38–1.61 (m, 10H, 5CH2-cyclohexyll), 3.65 (s, 2H, CH2-CO), 4.33–4.50 (m, 1H, CH-(CH3)2), 4.93 (br.s, 1H, NH), 7.14 (s, 2H, NH2), 7.27 (s, 2H, Har.), 7.36–7.48 (m, 3H, Har.); 13C NMR (CDCl3, δ, ppm): 20.68 CH3), 22.49, 25.85, 29.68 (3CH2-cyclohexyl), 46.79 (CH2-CO), 53.57 (CH-(CH3)2), 66.06 (Cq), 129.61, 129.75, 129.87, 134.78 (aromatic carbons), 148.23, 156.44, 157.21 (3C = O, imidazolidine), 164.89, 166.19 (2C = O), MS (EI) m/z (%): 429.48 (M+, 10%), Anal. calcd. for C21H27N5O5: C, 58.73; H, 6.34; N, 16.31. Found: C, 58.75; H, 6.34; N, 16.30.
4.1.4.7. 1-(2-((3-Butyl-2,4,5-trioxo imidazolidin-1-yl) amino)- N-phenyl acetamido) cyclohexane-1-carboxamide (9c)
White solid, m.p. 170°C, yield 75%, HPLC: purity 97.6%, Rt = 6.59 min. “1HNMR” (CDCl3d6, δ, ppm): 0.96 (t, 3H, J = 4 Hz, CH3), 1.25 36-1.41 (m, 2H, CH2- CH3), 1.61–1.63 (m, 10H, 5CH2-cyclohexyl), 3.66 (s, 2H, CH2-CO), 3.73 (t, 2H, CH2-(CH2)2 -CH3), 4.54 (br.s, 1H, NH), 7.18 (s, 2H, Har.), 7.26 (br.s, 2H, NH2), 7.27–7.46 (m, 3H, Har.). 13CNMR (CDCl3d6, δ, ppm): 13.73 (CH3), 19.89 (CH2-CH3), 20.04, 22.51, 29.82 (3CH2-cyclohexyl), 29.96 (CH2-CH2- CH3), 42.90 (CH2-CH2- CH2-CH3), 53.42 (CH2-CO), 63.23 (Cq), 129.61, 129.82, 130.08, 136.56, 137.38 (aromatic carbons.), 148.78, 151.81, 153.71 (3C = O, imidazolidine), 165.06, 167.69 (2C = O). MS (EI) m/z (%): 443.50 (M+, 30%), IR (KBr, cm− 1) 3392, 3385, 3275 (NH, NH2), 1795, 1759, 1685, 1670, 1593 (5C = O); Anal. calcd. for C22H29N5O5: C, 59.58; H, 6.59; N, 15.79. Found: C, 59.55; H, 6.62; N, 15.83.
4.1.4.8. 1-(2-((3-Benzyl-2,4,5- trioxo imidazolidin-1-yl) amino)-N-phenyl acetamido) cyclohexane-1-carboxamide (9d)
White solid, m.p. 175°C, yield 90%, HPLC: purity 97.9%, Rt = 8.25 min. “1HNMR” (CDCl3d6, δ, ppm): 1.25 (s, 4H, 2CH2-cyclohexyl), 1.46–1.72 (m, 6H, 3CH2-cyclohexyl), 4.84 (s, 2H, CH2-CO), 4.87 ( s, 2H, CH2-C6H5),7.25 (s, 2H, NH2), 7.35–7.37 (m, 10H, Har.) 7.50 (br.s, 1H, NH). 13CNMR (CDCl3d6, δ, ppm): 22.89, 34.52, 34.58 (3CH2-cyclohexyl), 43.52 (CH2-C6H5), 44.03 (CH2-CO), 64.40 (Cq), 128.79, 128.97, 129.01, 129.03, 129.12, 129.18, 133.82, 134.99 (aromatic carbons), 149.94, 151.59, 153.31 (3C = O, imidazolidine), 164.89, 166.19 (2C = O), MS (EI) m/z (%): 477.52 (M+, 40), IR (KBr, cm− 1) 3400, 3332, 3294, 3215 (NH, NH2), 1730, 1693, 1680, 1662, 1602 (5C = O); Anal. calcd. for C25H27N5O5: C, 62.88; H, 5.70; N, 14.67. Found: C, 62.86; H,5.68; N, 14.63.
4.1.4.9. 1-(N-(p-Tolyl)-2-((2,4,5-trioxo-3-propylimidazolidin-1-yl)amino)acetamido)cyclohexane-1-carboxamide (10a)
White solid, m.p. 110–112°C, yield 75%, HPLC: purity 97%, Rt = 3.81 min. “1HNMR” (CDCl3d6, δ, ppm): 0.92 (t, 3H, J = 4 Hz, CH2-CH3), 1.56–1.59 (m, 2H, CH2-CH3), 1.66–1.73 (m, 10H, 5CH2-cyclohexyl), 1.79 (s, 3H, CH3), 3.85 (t, 2H, J = 8, CH2-CH2-CH3), 3.73 (s, 2H, CH2-CO), 4.53 (br.s, 1H, NH), 7.28 ( s, 2H, NH2), 7.36 (d, 2H, J = 8, Har.), 7.46 (d, 2H, J = 8 Hz, Har.). 13CNMR (CDCl3d6, δ, ppm): 11.10 (CH3-CH2), 21.14 (CH3-C6H5), 23.94, 24.17, 36.97 (3CH2-cyclohexyl), 42.39 (CH2-CH2-CH3), 44.46 (CH2-CO), 72.38 (Cq), 128.75, 129.56, 129.73, 140.71 (aromatic carbons), 149.0, 152.55, 154.54 (3C = O, imidazolidine), 172.28, 177.53 (2C = O). MS (EI) m/z (%): 443.50 (M+, 45%), IR (KBr, cm− 1) 3290, 3165, 3091, 3053 (NH, NH2), 1760, 1720, 1685, 1662, 1631 (5C = O); Anal. calcd. for C22H29N5O5: C, 59.58; H, 6.59; N, 15.79. Found: C, 59.54; H, 6.57; N, 15.78.
4.1.4.10. 1-(2- ((3-Isopropyl − 2,4,5 –trioxo imidazolidin-1-yl) amino)-N- (p-tolyl) acetamido) cyclohexane-1-carboxamide (10b)
White solid, m.p. 150–152°C, yield 83%, HPLC: purity 99%, Rt = 5.94 min. “1HNMR” (CDCl3d6, δ, ppm): 1.14 (d, 6H, J = 6.5 Hz, (CH3)2), 1.43–1.54 (m, 10H, 5CH2-cyclohexyl), 1.77 (s, 3H, C6H5-CH3), 3.87 (s, 2H, CH2-CO), 4.41–4.57 (m, 1H, CH-(CH3)2), 7.17 (d, 2H, J = 6.5 Hz, Har.), 7.27 (s, 2H, NH2), 7.44 (d, 2H, J = 6.5 Hz, Har.); “13C NMR” (CDCl3, δ, ppm): 20.42 (CH-(CH3)2), 21.15 (CH3-C6H5), 22.32, 25.16, 29.72 (3CH2-cyclohexyl), 46.17 (CH2-CO), 53.52 (CH-(CH3)2), 67.12 (Cq), 129.41, 129.65, 129.81, 135.73 (aromatic carbons), 148.21, 154.42, 157.13 (3C = O, imidazolidine), 164.42, 167.16 (2C = O), MS (EI) m/z (%): 443.50 (M+, 50%), IR (KBr, cm− 1) 3155, 3091, 3055, 3035 (NH, NH2), 1730, 1708, 1680, 1666, 1649 (5C = O); Anal. calcd. for C22H29N5O5: C, 59.58; H, 6.59; N, 15.79. Found: C, 59.57; H, 6.55; N, 15.77.
4.1.4.11. 1-(2-((3-Butyl − 2,4,5-trioxo imidazolidin-1-yl) amino)-N-(p-tolyl) acetamido) cyclohexane-1-carboxamide (10c)
White solid, m.p. 120°C, yield 75%, HPLC: purity 99%, Rt = 6.07 min. “1HNMR” (CDCl3d6, δ, ppm): 0.86 (t, 3H, J = 4.4 Hz, CH2-CH3), 1.24–1.30 (m, 2H, CH2-CH2-CH3), 1.24–1.30 (m, 2H, CH2-CH2-CH3), 1.47–1.69 (m, 10H, 5CH2-cyclohexyl), 1.97 (s, 3H, C6H4-CH3), 3.58 (s, 2H, CH2-CO), 3.80 (t, 2H, J = 7.4 Hz, CH2-(CH2)2 -CH3), 4.49 (br.s, 1H, NH), 7.20 (br.s, 2H, NH2), 7.27 (d, 2H, J = 8.4 Hz, Har.), 7.31 (d, 2H, J = 8.4 Hz, Har.). MS (EI) m/z (%): 457.53 (M+, 15%), IR (KBr, cm− 1) 3385, 3311, 3301 (NH, NH2), 1759, 1719, 1680, 1665, 1631, 1625 (5C = O); Anal. calcd. for C23H31N5O5: C, 60.38; H, 6.83; N, 15.31. Found: C, 60.36; H, 6.81; N, 15.30.
4.1.4.12. 1-(2-((3-Benzyl − 2,4,5- trioxoimidazolidin-1-yl)amino)-N-(p-tolyl)acetamido)cyclohexane-1-carboxamide (10d)
White solid, m.p. 160°C, yield 75%, HPLC: purity 95.9%, Rt = 6.60 min. “1HNMR” (CDCl3d6, δ, ppm): 1.19–1.37 (m, 10H, 5CH2-cyclohexyl), 1.74 (CH3-C6H4), 3.66 (s, 2H, CH2-CO), 4.77 (s, 2H, CH2-C6H5), 4.85 (br.s, 1H, NH), 5.29 (s, 2H, NH2), 7.17–7.42 (m, 10H, Har.). 13CNMR (CDCl3d6, δ, ppm): 20.7 (CH3), 22.4, 25.1, 36.9 (2CH2-cyclohexyl), 44.6 (CH2-C6H5), 53.1 (CH2-CO), 70.9 (Cq), 129.06, 129.54, 129.64, 129.68, 129.77, 133.81, 137.05, 136.57 (aromatic carbons), 150.41, 154.44, 159.31 (3C = O, imidazolidine), 166.20, 177.51 (2C = O). MS (EI) m/z (%): 491.55 (M+, 30%), IR (KBr, cm− 1) 3307, 3273, 3062, 3032 (NH, NH2), 1759, 1720, 1680, 1665, 1631, 1625 (5C = O); Anal. calcd. for C26H29N5O5: C, 63.53; H, 5.95; N, 14.25. Found: C, 63.50; H, 5.61; N, 14.27.