2-(cyclohexylamino)ethanol

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Hydroxyethylamine and cyclohexanone were reacted according to Method B4a, Step 1 to afford 4-aza-1-oxaspiro[4.5]decane. The oxazolidine was reduced according to method B4a, Step 2 to afford N-cyclohexyl-N-(2-hydroxyethyl)amine. The alcohol was reacted with SOCl2 according to Method B7c to afford N-cyclohexyl-N-(2-chloroethyl)amine. The amine was reacted with 2-methoxy-4-nitrophenyl isothiocyanate according to Method C1d to afford 2-(2-methyl-4-nitrophenylimino)-3-cyclohexyl-1,3-thiazolidine.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Hydroxyethylamine and cyclohexanone were reacted according to Method B4a, Step 1 to afford 4-aza-1-oxaspiro[4.5]decane. The oxazolidine was reduced according to method B4a, Step 2 to afford N-cyclohexyl-N-(2-hydroxyethyl)amine. The alcohol was reacted with SOCl2 according to Method B7c to afford N-cyclohexyl-N-(2-chloroethyl)amine. The amine was reacted with 2-methoxy-4-nitrophenyl isothiocyanate according to Method C1d to afford 2-(2-methyl-4-nitrophenylimino)-3-cyclohexyl-1,3-thiazolidine.

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 0.24 g (1.7 mmol) of 2-cyclohexylaminoethanol are added to a suspension of 130 mg (0.34 mmol) of (E)-N-(4′-chlorobiphenyl-4-yl)-3-(4-chloromethylphenyl)acrylamide in 10 mL of DMF and the mixture is stirred for 48 hours at 80° C. Then the reaction mixture is poured onto water and the precipitate formed is suction filtered and washed with water. The solid is dried in the circulating air dryer at 50° C. Yield: 20 mg (10% of theory); C30H33ClN2O2 (M=489.05); melting point: 178° C.-179° C.; calc.: molecular ion peak (M+H)+: 489/491 (Cl); found: molecular ion peak (M+H)+: 489/491 (Cl). Then the reaction mixture is poured onto water the precipitate formed filtered washed with water The solid is dried in the circulating air dryer at 50° C

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Following the procedure for 103, 8-(1H-Pyrazol-4-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid (50.0 mg, 0.2 mmol) was reacted with 2-(cyclohexylamino)ethanol (1.2 equiv) to give 173 (14.1 mg, M+1 439.1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of N-cyclohexylethanolamine (2.1 g, 14.7 mmol) and tetrahydrofuran (70 ml) were added iodomethane (1.1 ml, 17.6 mmol) and triethylamine (2.26 ml, 16.2 mmol) at room temperature, and the reaction mixture was stirred for 1 hour under heating refluxing. The reaction mixture was cooled at room temperature (external temperature). To the mixture was added water to stop the reaction. To the reaction mixture was added ethyl acetate, and the organic layer was separated. The organic layer was washed with water and an aqueous saturated sodium chloride solution, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate, NH silica gel) to obtain the title compound (790.7 mg, 5.0 mmol, 34%). under heating refluxing the reaction the organic layer was separated The organic layer was washed with water an aqueous saturated sodium chloride solution, and the solvent was distilled off under reduced pressure The residue was purified by silica gel chromatography (ethyl acetate, NH silica gel)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To an ice cooled solution of N-cyclohexylethanolamine (0.55 g, 3.9 mmol) and 4-tert-butoxycarbonylamino-4-cyclohexyl-butyric acid (1.0 g, 3.5 mol), in DCM (200 mL), HOBT (0.62 g, 4.5 mmol) and TEA (1.0 mL) were added followed by addition of 1,3-dimethylamino propyl-3-ethylcarbodiimide (EDC, 0.87 g, 4.5 mmol). The reaction mixture was allowed to warm to room temperature and then stirred overnight. EtOAc (300 mL) was added to the reaction mixture. The reaction mixture was then washed with aqueous citric acid solution, saturated NaHCO3 solution, and NaCl solution. The organic layer was collected, dried with MgSO4, and then evaporated to yield {1-cyclohexyl-3-[cyclohexyl-(2-hydroxy-ethyl)-carbamoyl]-propyl}-carbamic acid tert-butyl ester as an oil, which was used in the next step without further purification. The reaction mixture was then washed with aqueous citric acid solution, saturated NaHCO3 solution, and NaCl solution The organic layer was collected dried with MgSO4 evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Hydroxyethylamine and cyclohexanone were reacted according to Method B4a, Step 1 to afford 4-aza-1-oxaspiro[4.5]decane. The oxazolidine was reduced according to method B4a, Step 2 to afford N-cyclohexyl-N-(2-hydroxyethyl)amine. The alcohol was reacted with SOCl2 according to Method B7c to afford N-cyclohexyl-N-(2-chloroethyl)amine. The amine was reacted with 2-methoxy-4-nitrophenyl isothiocyanate according to Method C1d to afford 2-(2-methyl-4-nitrophenylimino)-3-cyclohexyl-1,3-thiazolidine.

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Following the procedure for 103, 8-(1H-Pyrazol-4-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid (50.0 mg, 0.2 mmol) was reacted with 2-(cyclohexylamino)ethanol (1.2 equiv) to give 173 (14.1 mg, M+1 439.1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Following the procedure for 103, 8-(1H-Pyrazol-4-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid (50.0 mg, 0.2 mmol) was reacted with 2-(cyclohexylamino)ethanol (1.2 equiv) to give 173 (14.1 mg, M+1 439.1)