2-[1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidin-2-yl]acetic acid

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

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

Procedure: Trimethylsilyldiazomethane (2 M solution in hexane, 1.5 ml) was added dropwise to a mixed solution of tert-butyl 2-carboxymethylpyrrolidine-1-carboxylate (CAS No. 194154-91-1, 500 mg) in methanol (1 ml)-toluene (1 ml) under ice-cooling, and the reaction solution was stirred at the same temperature for three hours. The reaction solution was concentrated. The resulting residue was purified by silica gel column chromatography (elution solvent: heptane-ethyl acetate system) to obtain 506 mg of the title compound. The property values of the compound are as follows. The reaction solution was concentrated The resulting residue was purified by silica gel column chromatography (elution solvent: heptane-ethyl acetate system)

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

Procedure: N1-(Benzo[d]isothiazol-3-yl)-N3-((4′-methoxybiphenyl-4-yl)methyl)propane-1,3-diamine (100 mg, 0.25 mmol), 2-carboxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (68 mg, 0.34 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarboduimide hydrochloride (58 mg, 0.30 mmol) were dissolved in anhydrous methylene chloride (10 mL). Diisopropylethylamine (52 μL, mmol) added to the mixture. The reaction was allowed to stir overnight at room temperature. The solution was washed with water, then dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by column chromatography, on silica gel, eluting with a mixture of 3:1 hexanes:ethyl acetate yielded tert-butyl 2-(2-((3-(benzo[d]isothiazol-3-ylamino)propyl)((4′-methoxybiphenyl-4-yl)methyl)amino)-2-oxoethyl)pyrrolidine-1-carboxylate as a solid (30 mg). 1H NMR (300 MHz, CDCl3): 7.90-7.95 (m, 1H), 7.75-7.85 (m, 1H), 7.35-7.55 (m, 6H), 7.19-7.25 (m, 2H), 6.95-7.00 m, 2H), 4.90-5.00 (m, 1H), 4.55-4.65 (m, 2H), 4.19-4.25 (m, 1H), 3.85 (s, 3H), 3.55-3.65 (m, 2H), 3.30-3.35 (m, 2H), 3.10-3.19 (m, 1H), 2.35-2.45 (m, 1H), 2.05-2.15 (m, 1H), 1.80-1.90 (m, 4H), 1.50 ppm (s, 9H). MW=615 confirmed by LC-MS, tr=5.12 min (Method B) MH+=614-616. The solution was washed with water dried over anhydrous sodium sulfate concentrated under reduced pressure Purification by column chromatography on silica gel, eluting with a mixture of 3:1 hexanes

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

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

Procedure: Trimethylsilyldiazomethane (2 M solution in hexane, 1.5 ml) was added dropwise to a mixed solution of tert-butyl 2-carboxymethylpyrrolidine-1-carboxylate (CAS No. 194154-91-1, 500 mg) in methanol (1 ml)-toluene (1 ml) under ice-cooling, and the reaction solution was stirred at the same temperature for three hours. The reaction solution was concentrated. The resulting residue was purified by silica gel column chromatography (elution solvent: heptane-ethyl acetate system) to obtain 506 mg of the title compound. The property values of the compound are as follows. The reaction solution was concentrated The resulting residue was purified by silica gel column chromatography (elution solvent: heptane-ethyl acetate system)

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

Procedure: N1-(Benzo[d]isothiazol-3-yl)-N3-((4′-methoxybiphenyl-4-yl)methyl)propane-1,3-diamine (100 mg, 0.25 mmol), 2-carboxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (68 mg, 0.34 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarboduimide hydrochloride (58 mg, 0.30 mmol) were dissolved in anhydrous methylene chloride (10 mL). Diisopropylethylamine (52 μL, mmol) added to the mixture. The reaction was allowed to stir overnight at room temperature. The solution was washed with water, then dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by column chromatography, on silica gel, eluting with a mixture of 3:1 hexanes:ethyl acetate yielded tert-butyl 2-(2-((3-(benzo[d]isothiazol-3-ylamino)propyl)((4′-methoxybiphenyl-4-yl)methyl)amino)-2-oxoethyl)pyrrolidine-1-carboxylate as a solid (30 mg). 1H NMR (300 MHz, CDCl3): 7.90-7.95 (m, 1H), 7.75-7.85 (m, 1H), 7.35-7.55 (m, 6H), 7.19-7.25 (m, 2H), 6.95-7.00 m, 2H), 4.90-5.00 (m, 1H), 4.55-4.65 (m, 2H), 4.19-4.25 (m, 1H), 3.85 (s, 3H), 3.55-3.65 (m, 2H), 3.30-3.35 (m, 2H), 3.10-3.19 (m, 1H), 2.35-2.45 (m, 1H), 2.05-2.15 (m, 1H), 1.80-1.90 (m, 4H), 1.50 ppm (s, 9H). MW=615 confirmed by LC-MS, tr=5.12 min (Method B) MH+=614-616. The solution was washed with water dried over anhydrous sodium sulfate concentrated under reduced pressure Purification by column chromatography on silica gel, eluting with a mixture of 3:1 hexanes

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