piperazin-1-yl(pyrrolidin-1-yl)methanone

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

Procedure: (2E)-4-Bromobut-2-enoic acid (106 mg, 0.64 mmol) and piperazin-1-yl(pyrrolidin-1-yl)methanone (125 mg, 0.68 mmol) were dissolved in DCM (5.0 mL), and DIPEA (111 mg, 0.85 mmol) was added. The mixture was stirred at rt for 2 h. Subsequently, the compound from Example 15A (150 mg, 0.43 mmol), DIPEA (55 mg, 0.43 mmol) and EDCI (82 mg, 0.43 mmol) were added. The reaction was stirred at 50° C. overnight. Then, water was added, and the mixture was extracted three times with DCM. The combined organic layers were dried over sodium sulfate. The solvent was removed in vacuo, and the residue was purified by preparative HPLC to yield 25 mg (10%) of the title compound. The reaction was stirred at 50° C. overnight the mixture was extracted three times with DCM The combined organic layers were dried over sodium sulfate The solvent was removed in vacuo the residue was purified by preparative HPLC

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

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

Procedure: (2E)-4-Bromobut-2-enoic acid (106 mg, 0.64 mmol) and piperazin-1-yl(pyrrolidin-1-yl)methanone (125 mg, 0.68 mmol) were dissolved in DCM (5.0 mL), and DIPEA (111 mg, 0.85 mmol) was added. The mixture was stirred at rt for 2 h. Subsequently, the compound from Example 15A (150 mg, 0.43 mmol), DIPEA (55 mg, 0.43 mmol) and EDCI (82 mg, 0.43 mmol) were added. The reaction was stirred at 50° C. overnight. Then, water was added, and the mixture was extracted three times with DCM. The combined organic layers were dried over sodium sulfate. The solvent was removed in vacuo, and the residue was purified by preparative HPLC to yield 25 mg (10%) of the title compound. The reaction was stirred at 50° C. overnight the mixture was extracted three times with DCM The combined organic layers were dried over sodium sulfate The solvent was removed in vacuo the residue was purified by preparative HPLC

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

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

Procedure: (2E)-4-Bromobut-2-enoic acid (106 mg, 0.64 mmol) and piperazin-1-yl(pyrrolidin-1-yl)methanone (125 mg, 0.68 mmol) were dissolved in DCM (5.0 mL), and DIPEA (111 mg, 0.85 mmol) was added. The mixture was stirred at rt for 2 h. Subsequently, the compound from Example 15A (150 mg, 0.43 mmol), DIPEA (55 mg, 0.43 mmol) and EDCI (82 mg, 0.43 mmol) were added. The reaction was stirred at 50° C. overnight. Then, water was added, and the mixture was extracted three times with DCM. The combined organic layers were dried over sodium sulfate. The solvent was removed in vacuo, and the residue was purified by preparative HPLC to yield 25 mg (10%) of the title compound. The reaction was stirred at 50° C. overnight the mixture was extracted three times with DCM The combined organic layers were dried over sodium sulfate The solvent was removed in vacuo the residue was purified by preparative HPLC

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

Procedure: The same procedure described in step c method J was followed but starting from 2-(5-bromo-2-fluoro-phenyl)-1-methyl-1H-benzoimidazole and piperazin-1-yl-pyrrolidin-1-yl-methanone. The crude reaction mixture was purified by preparative HPLC to afford 0.06 g of the title compound (44%). The crude reaction mixture was purified by preparative HPLC

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

Procedure: The title compound was prepared from 5-(4-methylphenyl)isoxazole-4-carboxylic acid (10.2 mg, 0.050 mmol) and piperazin-1-yl-pyrrolidin-1-yl-methanone (11.0 mg, 0.060 mmol) as described in synthetic method B and thereafter purified by preparative HPLC method B to give a solid (11.7 mg). Calcd for C20H24N4O3: 368.1848, found 368.1847. purified by preparative HPLC method B