tert-Butyl 4-(5-amino-1H-indol-3-yl)cyclohex-3-enyl(methyl)carbamate → HCID 178486004, compound
Reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[C:11]1[CH2:16][CH2:15][CH:14]([N:17]([CH3:25])[C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH2:13][CH:12]=1.I.CS[C:29]([C:31]1[S:32][CH:33]=[CH:34][CH:35]=1)=[NH:30]>C(O)C>[CH3:25][N:17]([CH:14]1[CH2:15][CH2:16][C:11]([C:5]2[C:4]3[C:8](=[CH:9][CH:10]=[C:2]([NH:1][C:29]([C:31]4[S:32][CH:33]=[CH:34][CH:35]=4)=[NH:30])[CH:3]=3)[NH:7][CH:6]=2)=[CH:12][CH2:13]1)[C:18](=[O:24])[O:19][C:20]([CH3:21])([CH3:22])[CH3:23]Participants
4
Procedure
A solution of compound 98 (0.415 g, 1.215 mmol) in dry ethanol (20 mL) was treated with thiophene-2-carboximidothioic acid methyl ester hydroiodide (0.693 g, 2.430 mmol) at room temperature and the resulting solution was stirred for 24 h. The solvent was evaporated and crude was diluted with sat. NaHCO3 solution (25 mL) and CH2Cl2 (50 mL). The organic layer was separated and aqueous layer was extracted with CH2Cl2 (2 25 mL). The combined organic layer was washed with brine (20 mL) and dried (Na2SO4). Th solvent was evaporated and crude product was purified by column chromatography on silica gel (2M NH3 in methanol: CH2Cl2, 5:95) to obtain compound 99 (0.37 g, 68%) as a foam. 1H NMR (DMSO-d6) δ: 0.85 (t, 1H, J=7.2 Hz), 1.20-1.26 (m, 1H), 1.40 (s, 9H), 1.77-1.87 (m, 2H), 2.22-2.40 (m, 2H), 2.72 (s, 3H), 4.06-4.16 (m, 1H), 6.06 (s, 1H), 6.28 (brs, 1H), 6.66 (d, 1H, J=8.4 Hz), 7.10 (t, 1H, J=4.2 Hz), 7.22 (s, 1H), 7.25-7.32 (m, 2H), 7.60 (d, 1H, J=4.8 Hz), 7.72 (d, 1H, J=3.3 Hz), 10.94 (s, 1H); ESI-MS m/z (%): 451 (MH+, 100). N-(3-(4-(methylamino)cyclohex-1-enyl)-1H-indol-5-yl)thiophene-2-carboximidamide (100): A solution of compound 99 (0.35 g, 0.776 mmol) was treated with 20% TFA in CH2Cl2 (20 mL) at 0° C. and stirring was continued for 1 h at the same temperature. The solvent was evaporated and crude was diluted with 10% aq. NH3 (15 mL) and product was extracted into CH2Cl2 (3 20 mL). The combined CH2Cl2 layer was washed with brine (10 mL) and dried (Na2SO4). The solvent was evaporated and the crude product was purified by column chromatography (2 M NH3 in methanol: CH2Cl2, 1:9) to obtain compound 100 (0.2 g, 74%) as a solid. mp 167-169° C.; 1H NMR (DMSO-d6) δ: 1.39-1.47 (m, 2H), 1.88-1.96 (m, 3H), 2.33 (s, 3H), 2.40-2.46 (m, 1H), 2.57-2.61 (m, 1H), 6.01 (s, 1H), 6.19 (brs, 2H), 6.65 (dd, 1H, J=1.5, 8.2 Hz), 7.09 (dd, 1H, J=4.2, 4.9 Hz), 7.20 (s, 1H), 7.28-7.31 (m, 2H), 7.59 (d, 1H, J=4.2 Hz), 7.71 (d, 1H, J=3.3 Hz), 10.87 (s, 1H); ESI-MS m/z (%): 351 (MH+, 66), 320 (54), 160 (63), 119 (100); ESI-HRMS calculated for C20H23N4S (MH+), Calculated: 351.1654; Observed: 351.1637.