2-cyclohexylethanamine;hydrochloride

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

Procedure: Using a method similar to Example 14, using 6-(1-oxo-indan-5-yloxy)-nicotinamide (Intermediate 4, 536 mg, 2.00 mmol), 2-cyclohexylethylamine HCl ((Synthesis (1983), (5), 388-9), 393 mg, 2.40 mmol), Et3N (243 mg, 2.40 mmol), Ti(iPrO)4 (1.14 g, 4.00 mmol), TiCl4 (11.0M/DCM, 4.00 ml, 4.00 mmol), and NaBH3CN (251 mg, 4.00 mmol) gives the title compound (628 mg) as a yellow solid. Mass spectrum (ion spray): m/z=380 (M+1); 1HNMR (CDCl3): 8.59 (s, 1H), 8.15 (d, 1H), 7.38 (d, 1H), 6.99 (s, 1H), 6.95 (d, 1H), 6.94 (d, 1H), 5.89 (br. s, 2H), 4.24 (t, 1H), 3.01 (m, 1H), 2.82 (m, 1H), 2.75 (t, 2H), 2.45 (m, 1H), 1.88 (m, 1H), 1.74-1.62 (m, 5H), 1.43 (m, 2H), 1.38-1.13 (m, 4H), 0.93 (m, 2H).

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

Procedure: Using a method similar to Example 14, using 6-(1-oxo-indan-5-yloxy)-nicotinamide (Intermediate 4, 536 mg, 2.00 mmol), 2-cyclohexylethylamine HCl ((Synthesis (1983), (5), 388-9), 393 mg, 2.40 mmol), Et3N (243 mg, 2.40 mmol), Ti(iPrO)4 (1.14 g, 4.00 mmol), TiCl4 (1.0M/DCM, 4.00 ml, 4.00 mmol), and NaBH3CN (251 mg, 4.00 mmol) gives the title compound (628 mg) as a yellow solid. Mass spectrum (ion spray): m/z=380 (M+1); 1HNMR (CDCl3): 8.59 (s, 1H), 8.15 (d, 1H), 7.38 (d, 1H), 6.99 (s, 1H), 6.95 (d, 1H), 6.94 (d, 1H), 5.89 (br. s, 2H), 4.24 (t, 1H), 3.01 (m, 1H), 2.82 (m, 1H), 2.75 (t, 2H), 2.45 (m, 1H), 1.88 (m, 1H), 1.74-1.62 (m, 5H), 1.43 (m, 2H), 1.38-1.13 (m, 4H), 0.93 (m, 2H).

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

Procedure: Using a method similar to Example 14, using 6-(1-oxo-indan-5-yloxy)-nicotinamide (Intermediate 4, 536 mg, 2.00 mmol), 2-cyclohexylethylamine HCl ((Synthesis (1983), (5), 388-9), 393 mg, 2.40 mmol), Et3N (243 mg, 2.40 mmol), Ti(iPrO)4 (1.14 g, 4.00 mmol), TiCl4 (1.0M/DCM, 4.00 ml, 4.00 mmol), and NaBH3CN (251 mg, 4.00 mmol) gives the title compound (628 mg) as a yellow solid. Mass spectrum (ion spray): m/z=380 (M+1); 1HNMR (CDCl3): 8.59 (s, 1H), 8.15 (d, 1H), 7.38 (d, 1H), 6.99 (s, 1H), 6.95 (d, 1H), 6.94 (d, 1H), 5.89 (br. s, 2H), 4.24 (t, 1H), 3.01 (m, 1H), 2.82 (m, 1H), 2.75 (t, 2H), 2.45 (m, 1H), 1.88 (m, 1H), 1.74-1.62 (m, 5H), 1.43 (m, 2H), 1.38-1.13 (m, 4H), 0.93 (m, 2H).

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

Procedure: 158 mg (0.93 mmol) of CDI were added to a solution of 300 mg (0.93 mmol) of 2-(2-(phenylsulfonyl)ethylthio)nicotinic acid in DCM (8 ml), and the mixture was stirred for 1 h at RT. A solution of 151 mg (0.93 mmol) of 2-cyclohexylethylamine hydrochloride and 157 μL (0.93 mmol) of diisopropylethyl-amine in DCM (8 ml) was then added, and stirring was continued for a further 16 h at RT. The reaction solution was then washed in each case three times with sat. aq. ammonium chloride solution and saturated aqueous NaHCO3 solution. The organic phase was dried over MgSO4, filtered and concentrated in vacuo. 390 mg (0.90 mmol, 97%) of N-(2-cyclohexylethyl)-2-(2-(phenylsulfonyl)-ethyl-thio)nicotinamide were obtained as residue. MS: m/z 433.2 [M+H]+. stirring was continued for a further 16 h at RT The reaction solution was then washed in each case three times with sat. aq. ammonium chloride solution and saturated aqueous NaHCO3 solution The organic phase was dried over MgSO4 filtered concentrated in vacuo

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

Procedure: Using a method similar to Example 14, using 6-(1-oxo-indan-5-yloxy)-nicotinamide (Intermediate 4, 536 mg, 2.00 mmol), 2-cyclohexylethylamine HCl ((Synthesis (1983), (5), 388-9), 393 mg, 2.40 mmol), Et3N (243 mg, 2.40 mmol), Ti(iPrO)4 (1.14 g, 4.00 mmol), TiCl4 (11.0M/DCM, 4.00 ml, 4.00 mmol), and NaBH3CN (251 mg, 4.00 mmol) gives the title compound (628 mg) as a yellow solid. Mass spectrum (ion spray): m/z=380 (M+1); 1HNMR (CDCl3): 8.59 (s, 1H), 8.15 (d, 1H), 7.38 (d, 1H), 6.99 (s, 1H), 6.95 (d, 1H), 6.94 (d, 1H), 5.89 (br. s, 2H), 4.24 (t, 1H), 3.01 (m, 1H), 2.82 (m, 1H), 2.75 (t, 2H), 2.45 (m, 1H), 1.88 (m, 1H), 1.74-1.62 (m, 5H), 1.43 (m, 2H), 1.38-1.13 (m, 4H), 0.93 (m, 2H).

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

Procedure: Using a method similar to Example 14, using 6-(1-oxo-indan-5-yloxy)-nicotinamide (Intermediate 4, 536 mg, 2.00 mmol), 2-cyclohexylethylamine HCl ((Synthesis (1983), (5), 388-9), 393 mg, 2.40 mmol), Et3N (243 mg, 2.40 mmol), Ti(iPrO)4 (1.14 g, 4.00 mmol), TiCl4 (11.0M/DCM, 4.00 ml, 4.00 mmol), and NaBH3CN (251 mg, 4.00 mmol) gives the title compound (628 mg) as a yellow solid. Mass spectrum (ion spray): m/z=380 (M+1); 1HNMR (CDCl3): 8.59 (s, 1H), 8.15 (d, 1H), 7.38 (d, 1H), 6.99 (s, 1H), 6.95 (d, 1H), 6.94 (d, 1H), 5.89 (br. s, 2H), 4.24 (t, 1H), 3.01 (m, 1H), 2.82 (m, 1H), 2.75 (t, 2H), 2.45 (m, 1H), 1.88 (m, 1H), 1.74-1.62 (m, 5H), 1.43 (m, 2H), 1.38-1.13 (m, 4H), 0.93 (m, 2H).

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

Procedure: Using the procedure outlined in Example 96, 4-(4-formylisoquinolin-1-yloxy)-benzamide (Preparation 16) and 2-cyclohexylethylamine hydrochloride were converted to the title compound: RT=2.70 min; m/z (ES+)=404.0 [M+H]+.

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

Procedure: Using a method similar to Example 14, using 6-(1-oxo-indan-5-yloxy)-nicotinamide (Intermediate 4, 536 mg, 2.00 mmol), 2-cyclohexylethylamine HCl ((Synthesis (1983), (5), 388-9), 393 mg, 2.40 mmol), Et3N (243 mg, 2.40 mmol), Ti(iPrO)4 (1.14 g, 4.00 mmol), TiCl4 (1.0M/DCM, 4.00 ml, 4.00 mmol), and NaBH3CN (251 mg, 4.00 mmol) gives the title compound (628 mg) as a yellow solid. Mass spectrum (ion spray): m/z=380 (M+1); 1HNMR (CDCl3): 8.59 (s, 1H), 8.15 (d, 1H), 7.38 (d, 1H), 6.99 (s, 1H), 6.95 (d, 1H), 6.94 (d, 1H), 5.89 (br. s, 2H), 4.24 (t, 1H), 3.01 (m, 1H), 2.82 (m, 1H), 2.75 (t, 2H), 2.45 (m, 1H), 1.88 (m, 1H), 1.74-1.62 (m, 5H), 1.43 (m, 2H), 1.38-1.13 (m, 4H), 0.93 (m, 2H).

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

Procedure: 158 mg (0.93 mmol) of CDI were added to a solution of 300 mg (0.93 mmol) of 2-(2-(phenylsulfonyl)ethylthio)nicotinic acid in DCM (8 ml), and the mixture was stirred for 1 h at RT. A solution of 151 mg (0.93 mmol) of 2-cyclohexylethylamine hydrochloride and 157 μL (0.93 mmol) of diisopropylethyl-amine in DCM (8 ml) was then added, and stirring was continued for a further 16 h at RT. The reaction solution was then washed in each case three times with sat. aq. ammonium chloride solution and saturated aqueous NaHCO3 solution. The organic phase was dried over MgSO4, filtered and concentrated in vacuo. 390 mg (0.90 mmol, 97%) of N-(2-cyclohexylethyl)-2-(2-(phenylsulfonyl)-ethyl-thio)nicotinamide were obtained as residue. MS: m/z 433.2 [M+H]+. stirring was continued for a further 16 h at RT The reaction solution was then washed in each case three times with sat. aq. ammonium chloride solution and saturated aqueous NaHCO3 solution The organic phase was dried over MgSO4 filtered concentrated in vacuo

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

Procedure: Using a method similar to Example 14, using 6-(1-oxo-indan-5-yloxy)-nicotinamide (Intermediate 4, 536 mg, 2.00 mmol), 2-cyclohexylethylamine HCl ((Synthesis (1983), (5), 388-9), 393 mg, 2.40 mmol), Et3N (243 mg, 2.40 mmol), Ti(iPrO)4 (1.14 g, 4.00 mmol), TiCl4 (11.0M/DCM, 4.00 ml, 4.00 mmol), and NaBH3CN (251 mg, 4.00 mmol) gives the title compound (628 mg) as a yellow solid. Mass spectrum (ion spray): m/z=380 (M+1); 1HNMR (CDCl3): 8.59 (s, 1H), 8.15 (d, 1H), 7.38 (d, 1H), 6.99 (s, 1H), 6.95 (d, 1H), 6.94 (d, 1H), 5.89 (br. s, 2H), 4.24 (t, 1H), 3.01 (m, 1H), 2.82 (m, 1H), 2.75 (t, 2H), 2.45 (m, 1H), 1.88 (m, 1H), 1.74-1.62 (m, 5H), 1.43 (m, 2H), 1.38-1.13 (m, 4H), 0.93 (m, 2H).