(2S)-N-tert-butylpiperazine-2-carboxamide

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

Procedure: 4-[5-({1-[2,4-Bis(trifluoromethyl)benzyl]-1H-indazol-5-yl}methylidene)-4-oxo-4,5-dihydro-1,3-thiazol-2-yl]-N-tert-butylpiperazine-2-(S)-carboxamide was prepared from 5-[1-(2,4-Bis-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-ethylsulfanyl-thiazol-4-one and piperazine-2-(S)-carboxylic acid tert-butylamide following General Procedure C.

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

Procedure: 4-[5-({1-[2,4-Bis(trifluoromethyl)benzyl]-1H-indazol-5-yl}methylidene)-4-oxo-4,5-dihydro-1,3-thiazol-2-yl]-N-tert-butylpiperazine-2-(S)-carboxamide was prepared from 5-[1-(2,4-Bis-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-ethylsulfanyl-thiazol-4-one and piperazine-2-(S)-carboxylic acid tert-butylamide following General Procedure C.

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

Procedure: In a manner analogous to the method described in examples 8, (4S,5R)-2-(6-tert-butyl-4-ethoxy-pyridin-3-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl chloride (example 51) was coupled with (S)-piperazine-2-carboxylic acid tert-butylamide (Wako) to give the title compound. HR-MS (ES, m/z) calculated for C38H49Cl2N6O3 [(M+H)+] 707.3238, observed 707.3239.

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

Procedure: Analogously to Example 4, 5 g (27 mmol) of pyrazinecarboxylic acid tert-butylamide, 127 mg (0.27 mmol) of bicyclo[2.2.1]hepta-2,5-dienerhodium(I) chloride dimer and 353 mg (0.594 mmol) of 1-[1 (R)-(dicyclohexylphosphino)ethyl]-2(S)-(diphenylphosphino)ferrocene were hydrogenated for 20 hours in 70 ml of methanol at 100° C. and 50 bar. A conversion of 85 percent was determined by NMR. The enantiomeric excess (ee) was 49 percent according to GC analysis.

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

Procedure: 0.5 g (2.7 mmol) of pyrazinecarboxylic acid tert-butylamide (prepared according to Example 3), 26.9 mg (58 μmol) of bicyclo[2.2.1]hepta-2,5-dienerhodium(I) chloride dimer and 72 mg (121 μmol) of 1-[1 (R)-(dicyclohexylphosphino)ethyl]-2(S)-(diphenylphosphino)ferrocene were placed in an autoclave under argon. After the addition of 10 ml of degassed methanol, the autoclave was flushed three times with argon and twice with hydrogen. A hydrogen pressure of 50 bar was then applied. Hydrogenation was carried out at 70° C. for 20 hours. The autoclave was depressurized and flushed with nitrogen. The solvent was completely distilled off. The yield of the title compound was 0.50 g. A conversion of 80 percent was determined by NMR. The enantiomeric excess (ee) was 77.6 percent according to GC analysis. the autoclave was flushed three times with argon flushed with nitrogen The solvent was completely distilled off