N-cyclohexylpiperidine-4-carboxamide

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

Procedure: 200 mg (0.44 mmol) of the compound of Example 70A and 138 mg (0.66 mmol) of 4-(cyclohexylamino)carbonylpiperidine (for preparation see WO 2003031397) are heated with 91 μl (0.66 mmol) of triethylamine in 4 ml of DMSO at 120° C. for 7 h. After cooling, the entire reaction mixture is separated by preparative HPLC (method 6). 30 mg of the title compound are obtained. After cooling the entire reaction mixture is separated by preparative HPLC (method 6)

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

Procedure: 200 mg (0.44 mmol) of the compound of Example 70A and 138 mg (0.66 mmol) of 4-(cyclohexylamino)carbonylpiperidine (for preparation see WO 2003031397) are heated with 91 μl (0.66 mmol) of triethylamine in 4 ml of DMSO at 120° C. for 7 h. After cooling, the entire reaction mixture is separated by preparative HPLC (method 6). 30 mg of the title compound are obtained. After cooling the entire reaction mixture is separated by preparative HPLC (method 6)

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

Procedure: The title compound is prepared according to the reactions described above starting from 2-chloromethyl-pyrimidin-4-ylamine and piperidine-4-carboxylic acid cyclohexylamide; LC-MS A: tR=0.47 min; [M+H]+=318.12.

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

Procedure: The title compound is prepared according to the reactions described above starting from 4-chloro-3-nitro-benzaldehyde and piperidine-4-carboxylic acid cyclohexylamide yielding after reductive amination 1-(4-Chloro-3-nitro-benzyl)-piperidine-4-carboxylic acid cyclohexylamide LC-MS A: tR=0.67 min; [M+H]+=380.03 and reduction with stannous chloride the title compound LC-MS A: tR=0.63 min; [M+H]+=350.21. The title compound is prepared

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

Procedure: The title compound is prepared according to the reactions described above starting from 2-chloro-3-nitro-benzaldehyde and piperidine-4-carboxylic acid cyclohexylamide giving after reductive amination 1-(2-chloro-3-nitro-benzyl)-piperidine-4-carboxylic acid cyclohexylamide LC-MS B: tR=0.57 min; [M+H]+=380.14 and reduction with stannous chloride the title compound LC-MS A: tR=0.50 min; [M+H]+=350.20. The title compound is prepared

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

Procedure: Piperidine-4-carboxylic acid cyclohexylamide (1.5 g 7.132 mmol) and 3-nitroacetophenone (1.77 g, 10.7 mmol) are dissolved in MeOH (40 mL). Tetraisopropyl-orthotitanate (3.167 mL, 10.7 mmol) is added and the mixture is stirred at RT for 18 h. NaBH4 (539.6 mg, 14.3 mmol) is added carefully. The mixture is evaporated under reduced pressure. DCM (25 mL) and water (25 mL) are added, following by 1 M NaOH solution (50 mL). The organic phase is separated and the aqueous phase is extracted with DCM (25 mL). The combined organic phases are dried over MgSO4, filtered and concentrated. The crude residue is purified by flash chromatography on silica gel using a gradient of heptane/EtOAc 4:1 to EtOAc 100%. After concentration of the product-containing fractions, the title compound (0.375 g, 15%) is obtained as a colorless solid LC-MS A: tR=0.64 min; [M+H]+=360.26. Tetraisopropyl-orthotitanate (3.167 mL, 10.7 mmol) is added The mixture is evaporated under reduced pressure DCM (25 mL) and water (25 mL) are added The organic phase is separated the aqueous phase is extracted with DCM (25 mL) The combined organic phases are dried over MgSO4 filtered concentrated The crude residue is purified by flash chromatography on silica gel using a gradient of heptane/EtOAc 4:1 to EtOAc 100%

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

Procedure: 200 mg (0.44 mmol) of the compound of Example 70A and 138 mg (0.66 mmol) of 4-(cyclohexylamino)carbonylpiperidine (for preparation see WO 2003031397) are heated with 91 μl (0.66 mmol) of triethylamine in 4 ml of DMSO at 120° C. for 7 h. After cooling, the entire reaction mixture is separated by preparative HPLC (method 6). 30 mg of the title compound are obtained. After cooling the entire reaction mixture is separated by preparative HPLC (method 6)