2-pyrrolidin-1-ylpropanoic acid

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: 0.18 mL (1.31 mmol) triethylamine and 269 mg (0.84 mmol) TBTU are added successively to a solution of 100 mg (0.70 mmol) 2-pyrrolidin-1-yl-propionic acid in 10 mL THF. The solution is stirred for 1 h at RT and then 200 mg (0.66 mmol) 4-[5-(4-chloro-phenyl)-pyridin-2-ylethynyl]-phenylamine are added. The reaction solution is stirred overnight at RT. The reaction is incomplete. Therefore 100 mg (0.70 mmol) 2-pyrrolidin-1-yl-propionic acid in 10 mL THF is added to the reaction mixture (activated for 1 h by stirring with 0.18 mL (1.31 mmol) triethylamine and 269 mg (0.84 mmol) TBTU). The reaction solution is stirred for a further 16 h and diluted with NaHCO3 solution. The aqueous phase is extracted with EtOAc and the organic phase is dried over MgSO4. The solvent is eliminated i.vac. and further purification is carried out by column chromatography on silica gel (EtOAc/MeOH/NH3 8:2:0.2). The reaction solution is stirred overnight at RT The reaction solution is stirred for a further 16 h The aqueous phase is extracted with EtOAc the organic phase is dried over MgSO4 and further purification

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

Procedure: 0.18 mL (1.31 mmol) triethylamine and 269 mg (0.84 mmol) TBTU are added successively to a solution of 100 mg (0.70 mmol) 2-pyrrolidin-1-yl-propionic acid in 10 mL THF. The solution is stirred for 1 h at RT and then 200 mg (0.66 mmol) 4-[5-(4-chloro-phenyl)-pyridin-2-ylethynyl]-phenylamine are added. The reaction solution is stirred overnight at RT. The reaction is incomplete. Therefore 100 mg (0.70 mmol) 2-pyrrolidin-1-yl-propionic acid in 10 mL THF is added to the reaction mixture (activated for 1 h by stirring with 0.18 mL (1.31 mmol) triethylamine and 269 mg (0.84 mmol) TBTU). The reaction solution is stirred for a further 16 h and diluted with NaHCO3 solution. The aqueous phase is extracted with EtOAc and the organic phase is dried over MgSO4. The solvent is eliminated i.vac. and further purification is carried out by column chromatography on silica gel (EtOAc/MeOH/NH3 8:2:0.2). The reaction solution is stirred overnight at RT The reaction solution is stirred for a further 16 h The aqueous phase is extracted with EtOAc the organic phase is dried over MgSO4 and further purification

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

Procedure: 4-Bromo aniline (0.25 g, 1.45 mmol), 2-pyrrolidin-1-ylpropanoic acid (0.25 g, 1.74 mmol) and diisopropylethylamine (0.3 ml, 1.74 mmol) were dissolved in dimethylacetamide (5 ml). HBTU (0.66 g, 1.74 mmol) was subsequently added and the mixture was stirred overnight. The reaction mixture was added to water and extracted twice with ethyl acetate. The combined organics were washed several times with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to give the desired product. Yield: 0.43 g, 100%. LCMS method: 2, RT: 2.73 min; MI: 297-299 [M+1]. extracted twice with ethyl acetate The combined organics were washed several times with brine dried over anhydrous magnesium sulfate filtered concentrated in vacuo

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

Procedure: 0.18 mL (1.31 mmol) triethylamine and 269 mg (0.84 mmol) TBTU are added successively to a solution of 100 mg (0.70 mmol) 2-pyrrolidin-1-yl-propionic acid in 10 mL THF. The solution is stirred for 1 h at RT and then 200 mg (0.66 mmol) 4-[5-(4-chloro-phenyl)-pyridin-2-ylethynyl]-phenylamine are added. The reaction solution is stirred overnight at RT. The reaction is incomplete. Therefore 100 mg (0.70 mmol) 2-pyrrolidin-1-yl-propionic acid in 10 mL THF is added to the reaction mixture (activated for 1 h by stirring with 0.18 mL (1.31 mmol) triethylamine and 269 mg (0.84 mmol) TBTU). The reaction solution is stirred for a further 16 h and diluted with NaHCO3 solution. The aqueous phase is extracted with EtOAc and the organic phase is dried over MgSO4. The solvent is eliminated i.vac. and further purification is carried out by column chromatography on silica gel (EtOAc/MeOH/NH3 8:2:0.2). The reaction solution is stirred overnight at RT The reaction solution is stirred for a further 16 h The aqueous phase is extracted with EtOAc the organic phase is dried over MgSO4 and further purification

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

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To the 2-pyrrolidin-1-yl-propanoic acid (508 mg, 3.55 mmol) in DMF (10 mL), was added HATU (1.62 g, 4.26 mmol), 4-Amino-benzoic acid ethyl ester (645 mg, 3.90 mmol) and NMM (1.2 mL, 10.65 mmol) and stirred at 50° C. for 16 hours. The reaction mixture was diluted with ethyl acetate (50 mL) and washed with 1 N HCl, saturated NaHCO3, water, brine and dried over MgSO4. Filtration and concentration gave ethyl 4-(2-(pyrrolidin-1-yl)propanamido)benzoate. washed with 1 N HCl, saturated NaHCO3, water, brine dried over MgSO4 Filtration and concentration

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

Procedure: To the 2-pyrrolidin-1-yl-propanoic acid (200 mg, 1.4 mmol) in DMF (10 mL), was added HATU (586 mg, 1.5 mmol), 4-amino-benzoic acid ethyl ester (231 mg, 1.4 mmol) and DIPEA (0.5 mL, 2.8 mmol). The reaction mixture was stirred at room temperature for 16 hours, diluted with water and acetonitrile, purified by preparative HPLC, and lyophilized to give ethyl 4-(2-(pyrrolidin-1-yl)propanamido)benzoate. purified by preparative HPLC

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

Procedure: To the 2-pyrrolidin-1-yl-propanoic acid (200 mg, 1.4 mmol) in DMF (10 mL), was added HATU (586 mg, 1.5 mmol), 4-amino-benzoic acid ethyl ester (231 mg, 1.4 mmol) and DIPEA (0.5 mL, 2.8 mmol). The reaction mixture was stirred at room temperature for 16 hours, diluted with water and acetonitrile, purified by preparative HPLC, and lyophilized to give ethyl 4-(2-(pyrrolidin-1-yl)propanamido)benzoate. purified by preparative HPLC

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

Procedure: To the 2-pyrrolidin-1-yl-propanoic acid (200 mg, 1.4 mmol) in DMF (10 mL), was added HATU (586 mg, 1.5 mmol), 4-amino-benzoic acid ethyl ester (231 mg, 1.4 mmol) and DIPEA (0.5 mL, 2.8 mmol). The reaction mixture was stirred at room temperature for 16 hours, diluted with water and acetonitrile, purified by preparative HPLC, and lyophilized to give ethyl 4-(2-(pyrrolidin-1-yl)propanamido)benzoate. purified by preparative HPLC