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X. He et al. / European Journal of Medicinal Chemistry 54 (2012) 542e548
J ¼ 4.88 Hz, Cpr-CH), 1.12 (s, 6H, 2CH3), 1.17 (t, 3H, J ¼ 7.08 Hz, CH3),
1.49 (d, 1H, J ¼ 4.88 Hz, Cpr-CH), 4.05 (q, 2H, J ¼ 7.08 Hz, CH2), 7.15
(brs, 1H, NH), 7.56 (d, 2H, J ¼ 8.48 Hz, C3,5-ArH), 7.89 (d, 2H,
J ¼ 8.48 Hz, C2,6-ArH), 8.00 (brs, 1H, NH), 10.25 (brs, 1H, NH). 13C-
NMR (100 Hz, DMSO-d6): 13.7, 18.5, 22.6, 27.4, 28.2, 48.4, 60.2,
126.4, 128.2, 129.2, 132.1, 165.3, 170.6, 174.4. ESI-MS: 354.2
([M þ H]þ). Anal. calc. for C16H20ClN3O4 : C 54.32, H 5.70, N 11.88;
found: C 54.53, H 5.61, N 11.95.
([M þ H]þ). Anal. calc. for C17H20F3N3O4: C 52.71, H 5.20, N 10.85;
found : C 52.72, H 5.31, N 10.81.
5.1.2.14. Ethyl 2,2-dimethyl-1-(2-(4-nitrobenzoyl)hydrazinecarbox-
amido) cyclopropanecarboxylate (6n). Yield: 75%. Yellow solid. Mp:
155e156 ꢁC. 1H NMR (400 MHz, DMSO-d6): 0.79 (d, 1H, J ¼ 4.88 Hz,
Cpr-CH), 1.13 (s, 6H, 2CH3), 1.19 (t, 3H, J ¼ 7.04 Hz, CH3), 1.51 (d, 1H,
J ¼ 4.88 Hz, Cpr-CH), 4.06 (q, 2H, J ¼ 7.04 Hz, CH2), 7.23 (brs, 1H,
NH), 8.10 (brs, 1H, NH), 8.12 (d, 2H, J ¼ 8.72 Hz, C2,6-ArH), 8.33 (d,
2H, J ¼ 8.72 Hz, C3,5-ArH), 10.51 (brs, 1H, NH). ESI-MS: 365.3
([M þ H]þ). Anal. calc. for C16H20N4O6: C 52.74, H 5.53, N 15.38;
found: C 52.66, H 5.37, N 15.46.
5.1.2.8. Ethyl
1-(2-(2-chlorobenzoyl)hydrazinecarboxamido)-2,2-
dimethyl cyclopropanecarboxylate (6h). Yield: 85%. White solid.
Mp: 113e114 ꢁC. 1H-NMR (400 MHz, DMSO-d6): 0.80 (d, 1H,
J ¼ 4.92 Hz, Cpr-CH), 1.13 (s, 3H, 2CH3), 1.17 (t, 3H, J ¼ 7.04 Hz, CH3),
1.52 (d, 1H, J ¼ 4.92 Hz, Cpr-CH), 4.06 (q, 2H, J ¼ 7.04 Hz), 6.95 (brs,
1H, NH), 7.39e7.47 (m, 5H, ArH), 8.13 (brs, 1H, NH), 10.07 (brs, 1H,
NH). ESI-MS: 354.2 ([M þ H]þ). Anal. calc. for C16H20ClN3O4: C
54.32, H 5.70, N 11.88; found: C 54.42, H 5.51, N 11.93.
5.1.2.15. Ethyl 1-(2-(4-methoxybenzoyl)hydrazinecarboxamido)-2,2-
dimethyl cyclopropanecarboxylate (6o). Yield: 85%. White solid.
Mp: 153e154 ꢁC. 1H NMR (400 MHz, DMSO-d6): 0.79(d, 1H,
J ¼ 4.92 Hz, Cpr-CH), 1.13 (s, 6H, 2CH3), 1.19 (t, 3H, J ¼ 7.06 Hz, CH3),
1.49 (d, 1H, J ¼ 4.92 Hz, Cpr-CH), 3.81 (s, 3H, OCH3), 4.02 (q, 2H,
5.1.2.9. Ethyl
1-(2-(4-bromobenzoyl)hydrazinecarboxamido)-2,2-
J ¼ 7.06 Hz, CH2), 5.37 (brs, 1H, NH), 7.00 (d, 2H, J ¼ 8.88 Hz, C3,5
-
dimethyl cyclopropanecarboxylate (6i). Yield: 82%. White solid.
Mp: 101e102 ꢁC. 1H-NMR (400 MHz, DMSO-d6): 0.77 (d, 1H,
J ¼ 4.84 Hz, Cpr-CH), 1.12 (s, 6H, 2CH3), 1.17 (t, 3H, J ¼ 7.12 Hz, CH3),
1.49 (d, 1H, J ¼ 4.84 Hz, Cpr-CH), 4.05 (q, 2H, J ¼ 7.12 Hz, CH2), 7.15
(brs, 1H, NH), 7.69 (d, 2H, J ¼ 8.44 Hz, C3,5-ArH), 7.82 (d, 2H,
J ¼ 8.44 Hz, C2,6-ArH), 8.00 (brs, 1H, NH), 10.25 (brs, 1H, NH). ESI-
MS: 398.1 ([M þ H]þ). Anal. calc. for C16H20BrN3O4: C 48.25, H
5.06, N 10.55; found: C 48.32, H 5.23, N 10.32.
ArH), 7.86 (d, 2H, J ¼ 8.88 Hz, C2,6-ArH), 10.03 (brs, 1H, NH), 11.72
(brs, 1H, NH). ESI-MS: 350.1 ([M þ H]þ). Anal. calc. for C17H23N3O5:
C 58.44, H 6.64, N 12.03; found: C 58.62, H 6.52, N 12.22.
5.1.2.16. Ethyl 1-(2-(3,4-dimethoxybenzoyl)hydrazinecarboxamido)-
2,2-dimethylcyclopropanecarboxylate (6p). Yield: 85%. White solid.
Mp: 134e135 ꢁC. 1H NMR (400 MHz, DMSO-d6): 0.78 (d, 1H,
J ¼ 4.80 Hz, Cpr-CH), 1.16 (s, 6H, 2CH3), 1.18 (t, 3H, J ¼ 7.00 Hz, CH3),
1.50 (d, 1H, J ¼ 4.80 Hz, Cpr-CH), 3.80 (s, 6H, 2OMe), 4.05 (q, 2H,
J ¼ 7.00 Hz, CH2), 7.01e7.07 (m, 2H, C4,5-ArH), 7.47 (brs, 1H, NH),
7.49e7.51 (m, 1H, C2-ArH), 7.92 (brs, 1H, NH), 10.04 (brs, 1H, NH).
ESI-MS: 380.1 ([M þ H]þ). Anal. calc. for C18H25N3O6 : C 56.98, H
6.64, N 11.08; found : C 56.82, H 6.42, N 11.12.
5.1.2.10. Ethyl 1-(2-(2-bromobenzoyl)hydrazinecarboxamido)-2,2-
dimethyl cyclopropanecarboxylate (6j). Yield: 88%. White solid.
M.p. 94e96 ꢁC.1H-NMR (400 MHz, DMSO-d6): 0.79(d,1H, J ¼ 4.64 Hz,
Cpr-CH), 1.14(s, 6H, 2CH3), 1.19(t, 3H, J ¼ 7.14 Hz, CH3), 1.51(d, 1H,
J ¼ 4.64 Hz, Cpr-CH), 4.07(q, 2H, J ¼ 7.14 Hz, CH2), 7.15(brs, 1H, NH),
7.31e7.35 (m, 2H), 7.36e7.54 (m, 2H), 8.25 (brs,1H, NH),10.15(brs,1H,
NH). ESI-MS: 398.1 ([M þ H]þ). Anal. calc. for C16H20BrN3O4: C 48.25,
H 5.06, N 10.55; found: C 48.34, H 5.30, N 10.44.
5.1.2.17. Ethyl
amido)-2,2-dimethylcyclopropanecarboxylate
1-(2-(3,4,5-trimethoxybenzoyl)hydrazinecarbox-
(6q). Yield: 85%.
White solid. Mp: 187e188 ꢁC. 1H-NMR (400 MHz, DMSO-d6): 0.78
(d,1H, J ¼ 4.96 Hz, Cpr-CH), 1.13 (s, 6H, 2CH3), 1.19 (t, 3H, J ¼ 7.08 Hz,
CH3), 1.51 (d, 1H, J ¼ 4.96 Hz, Cpr-CH), 3.71 (s, 3H, C4-ArOCH3), 3.82
(s, 6H, C3,5-ArOCH3), 4.06 (q, 2H, J ¼ 7.08 Hz, CH2), 7.11 (brs,1H, NH),
7.22 (s, 2H, C2,6-ArH), 7.97 (brs, 1H, NH), 10.12 (brs, 1H, NH). ESI-MS:
410.1 ([M þ H]þ). Anal. calc. for C19H27N3O7: C 55.74, H 6.65, N
10.26; found: C 55.43, H 6.43, N 10.37.
5.1.2.11. Ethyl
1-(2-(4-fluorobenzoyl)hydrazinecarboxamido)-2,2-
dimethyl cyclopropanecarboxylate (6k). Yield: 83%. White solid.
Mp: 169e170 ꢁC. 1H-NMR (400 MHz, DMSO-d6): 0.78 (d, 1H,
J ¼ 4.68Hz, Cpr-CH),1.12(s, 6H, 2CH3),1.17 (t, 3H, J ¼ 7.08Hz, CH3),1.50
(d,1H, J ¼ 4.68 Hz, Cpr-CH), 4.05 (q, 2H, J ¼ 7.08 Hz), 7.13 (brs,1H, NH),
7.29e7.33 (m, 2H, C3,5-ArH), 7.93e7.97 (m, 2H, C2,6-ArH), 7.99 (brs,1H,
NH), 10.18 (brs, 1H, NH). ESI-MS: 338.3 ([M þ H]þ). Anal. calc. for
C16H20FN3O4: C 56.97, H 5.98, N 12.46; found: C 57.02, H 6.13, N 12.38.
5.1.2.18. Ethyl
1-(2-(4-(dimethylamino)benzoyl)hydrazinecarbox-
amido)-2,2-dimethylcyclopropanecarboxylate (6r). Yield:77%. White
solid. Mp: 186e187 ꢁC. 1H-NMR (400 MHz, DMSO-d6): 0.78 (d, 1H,
J¼ 4.92Hz, Cpr-CH),1.12(s, 6H, 2CH3),1.18 (t, 3H, J¼ 7.04Hz,CH3),1.50
5.1.2.12. Ethyl
1-(2-(2-fluorobenzoyl)hydrazinecarboxamido)-2,2-
dimethyl cyclopropanecarboxylate (6l). Yield: 88%. White solid.
Mp: 117e118 ꢁC. 1H NMR (400 MHz, DMSO-d6): 0.79 (d, 1H,
J ¼ 4.88 Hz, Cpr-CH), 1.13 (s, 6H, 2CH3), 1.19 (t, 3H, J ¼ 7.04 Hz, CH3),
1.51 (d, 1H, J ¼ 4.88 Hz, Cpr-CH), 4.06 (q, 2H, J ¼ 7.04 Hz, CH2), 7.01
(brs, 1H, NH), 7.27e7.32 (m, 2H, ArH), 7.53e7.54 (m, 1H, ArH),
7.65e7.66 (m, 1H, ArH), 8.10 (brs, 1H, NH), 9.99 (brs, 1H, NH). ESI-
MS: 338.2 ([M þ H]þ). Anal. calc. for C16H20FN3O4: C 56.97, H
5.98, N 12.46; found: C 57.12, H 6.11, N 12.23.
(d, J¼ 4.92 Hz,Cpr-CH), 2.97(s, 6H, 2CH3), 6.70 (d, 2H, J¼ 8.92Hz, C3,5
-
2H), 6.99 (brs,1H, NH), 7.75 (d, 2H, J ¼ 8.80 Hz, C2,6-2H), 7.82 (brs,1H,
NH), 9.81 (brs, 1H, NH). ESI-MS: 363.4 ([M þ H]þ). Anal. calc. for
C18H26N4O4: C 59.65, H 7.23, N 15.46; found: C 59.42, H 7.12, N 15.29.
5.1.2.19. Ethyl 1-(2-(furan-2-carbonyl)hydrazinecarboxamido)-2,2-
dimethylcyclopropane carboxylate (6s). Yield: 80%. White solid.
Mp: 120e121 ꢁC. 1H-NMR (400 MHz, DMSO-d6): 0.79 (d, 1H,
J ¼ 4.96 Hz, Cpr-CH), 1.13 (s, 6H, 2CH3), 1.17 (q, 3H, J ¼ 7.08 Hz, CH3),
1.49 (d, 1H, J ¼ 4.96 Hz, Cpr-CH), 4.05 (q, 2H, J ¼ 7.08 Hz, CH2), 6.64
(m, 1H, C4-ArH), 7.04 (brs, 1H, NH), 7.21 (brs, 1H, NH), 7.87e7.88 (m,
1H, C3-ArH), 7.89e7.90 (m, 1H, C5-ArH), 10.03 (brs, 1H, NH). ESI-MS:
310.2 ([M þ H]þ). Anal. calc. for C14H19N3O5: C 54.36, H 6.19, N
13.58; found: C 54.61, H 6.27, N 13.69.
5.1.2.13. Ethyl 2,2-dimethyl-1-(2-(4-(trifluoromethyl)benzoyl)hydra-
zinecarboxamido) cyclopropanecarboxylate (6m). Yield: 80%. White
solid. Mp: 138e139 ꢁC. 1H-NMR (400 MHz, DMSO-d6): 0.86 (d, 1H,
J ¼ 4.84 Hz, Cpr-CH), 1.13 (s, 6H, 2CH3), 1.18 (t, 3H, J ¼ 7.20 Hz, CH3),
1.51 (d, 1H, J ¼ 4.84 Hz, Cpr-CH), 4.05 (q, 2H, J ¼ 7.20 Hz, CH2), 7.21
(brs, 1H, NH), 7.87 (d, 2H, J ¼ 8.28 Hz, C3,5-ArH), 8.07 (d, 2H,
J ¼ 8.28 Hz, C2,6-ArH), 8.10 (brs, 1H, NH), 10.41 (brs, 1H, NH). 13C-
NMR (100 Hz, DMSO-d6): 13.2, 18.4, 22.3, 27.2, 28.8, 48.8, 61.2,
126.2, 128.0, 128.3, 164.7, 167.1, 171.2, 175.6. ESI-MS: 388.2
5.1.2.20. Ethyl 2,2-dimethyl-1-(2-(thiophene-2-carbonyl)hydrazine-
carboxamido)-cyclopropanecarboxylate (6t). Yield: 77%. White
solid. Mp: 180e181 ꢁC. 1H-NMR (400 MHz, DMSO-d6): 0.79(d, 1H,