1-methyl-1-phenylhydrazine

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

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

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: A mixture of 4-(diethylamino)salicylaldehyde (10 g, 52 mmol, obtained from Aldrich) dissolved in 80 ml of 2-propanol, and N-methyl-N-phenylhydrazine (6.8 ml, 63 mmol, obtained from Aldrich) was added to a 250 ml round bottom flask equipped with a reflux condenser and a magnetic stirrer. The reaction mixture was refluxed until 4-(diethylamino)salicylaldehyde completely reacted. After the termination of the reaction, the reaction mixture was cooled to room temperature. The crystals formed were filtered and washed repeatedly with cold 2-propanol and dried under vacuum to yield 12.9 g (84%) of 4-(diethylamino)salicylaldehyde N-methyl-N-phenylhydrazone. The melting point was found to be 75.5–76.5° C. (recrystallized from 2-propanol). The 1H-NMR spectrum (100 Mhz) of the product in CDCl3 was characterized by the following chemical shifts (in ppm): 11.53 (s, 1H, OH); 7.63 (s, 1H, N═CH); 7.50–6.80 (m, 6H, Ar); 6.26 (m, 2H, Ar); 3.37 (m, 7H, CH2CH3, NCH3); 1.18 (t, 6H, CH2CH3, J=7.0 Hz). An elemental analysis yielded the following results in weight percent: C, 72.61; H, 7.88; N, 14.20, which compared with calculated values for C18H23N3O in weight percent of: C, 72.70; H, 7.80; N, 14.13. equipped with a reflux condenser and a magnetic stirrer completely reacted After the termination of the reaction The crystals formed were filtered washed repeatedly with cold 2-propanol dried under vacuum

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

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

Procedure: In a 10 mL two-necked flask, the above prepared 5-(tetrahydro-pyran-4-yl)-6-(2,2,2-trifluoro-ethoxy)-nicotinic acid (50 mg, 164 μmol, Eq: 1.00) was combined with tetrahydrofuran (1.0 mL) and DMF (1 mL) to give a colorless solution. TBTU (78.9 mg, 246 μmol, Eq: 1.5) and N,N-diisopropylethylamine (106 mg, 143 μl, 819 μmol, Eq: 5) were added and the reaction mixture stirred for 10 min at rt before 1-methyl-1-phenylhydrazine (24.0 mg, 23.1 μl, 197 μmol, Eq: 1.2, CAN 618-40-6) was added and the reaction mixture kept overnight at rt. Work up: The reaction mixture was quenched with 1 M HCl (10 mL) and extracted with EtOAc (2×20 mL). The organic layers were washed with 1 M NaOH, then with H2O/NaCl sol., the combined organic layers were dried over Na2SO4 and concentrated in vacuo. Purification by flash chromatography (silica gel, 10 g, 15% to 50% EtOAc in heptane) delivered eventually 62 mg of the title compound as white foam; MS (EI) 410.2 (M+H)+. to give a colorless solution was added The reaction mixture was quenched with 1 M HCl (10 mL) extracted with EtOAc (2×20 mL) The organic layers were washed with 1 M NaOH with H2O/NaCl sol., the combined organic layers were dried over Na2SO4 concentrated in vacuo Purification by flash chromatography (silica gel, 10 g, 15% to 50% EtOAc in heptane)

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

Procedure: In a 10 mL two-necked flask, the above prepared 5-(tetrahydro-pyran-4-yl)-6-(2,2,2-trifluoro-ethoxy)-nicotinic acid (50 mg, 164 μmol, Eq: 1.00) was combined with tetrahydrofuran (1.0 mL) and DMF (1 mL) to give a colorless solution. TBTU (78.9 mg, 246 μmol, Eq: 1.5) and N,N-diisopropylethylamine (106 mg, 143 μl, 819 μmol, Eq: 5) were added and the reaction mixture stirred for 10 min at rt before 1-methyl-1-phenylhydrazine (24.0 mg, 23.1 μl, 197 μmol, Eq: 1.2, CAN 618-40-6) was added and the reaction mixture kept overnight at rt. Work up: The reaction mixture was quenched with 1 M HCl (10 mL) and extracted with EtOAc (2×20 mL). The organic layers were washed with 1 M NaOH, then with H2O/NaCl sol., the combined organic layers were dried over Na2SO4 and concentrated in vacuo. Purification by flash chromatography (silica gel, 10 g, 15% to 50% EtOAc in heptane) delivered eventually 62 mg of the title compound as white foam; MS (EI) 410.2 (M+H)+. to give a colorless solution was added The reaction mixture was quenched with 1 M HCl (10 mL) extracted with EtOAc (2×20 mL) The organic layers were washed with 1 M NaOH with H2O/NaCl sol., the combined organic layers were dried over Na2SO4 concentrated in vacuo Purification by flash chromatography (silica gel, 10 g, 15% to 50% EtOAc in heptane)

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

Procedure: The title compound was synthesized in analogy to the procedure described in Example 34 c), using 5-cyclopropyl-6-(2,2,2-trifluoro-ethoxy)-nicotinic acid (example 34b) and N-methyl-N-phenyl-hydrazine (CAN 618-40-6); MS (ESI) 366.2 (M+H)+.

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

Procedure: The title compound was synthesized in analogy to the procedure described in Example 34 c), using 5-cyclopropyl-6-(2,2,2-trifluoro-ethoxy)-nicotinic acid (example 34b) and N-methyl-N-phenyl-hydrazine (CAN 618-40-6); MS (ESI) 366.2 (M+H)+.

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

Procedure: The title compound was synthesized in analogy to Example 1 using 5-cyclohexyl-6-(2,2,2-trifluoro-ethoxy)-3-pyridinecarboxylic acid (example 12c) and 1-methyl-1-phenyl-hydrazine (CAN 618-40-6) as starting materials; MS (EI) 408.4 (M+H)+.

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

Procedure: The title compound was synthesized in analogy to Example 1 using 5-cyclopentyl-6-(2,2,2-trifluoro-ethoxy)-3-pyridinecarboxylic acid (example 14c) and 1-methyl-1-phenyl-hydrazine (CAN 618-40-6) as starting materials; LC-MS (UV peak area/ESI) 98.0%, 394.1737 (M+H)+.