Reaction #47474

Reaction equation

(S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid

(S)-2-[4-(2-Chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-amide

1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride salt

1-hydroxybenzotriazole

(R)-4-(3-amino-pyrazol-1-ylmethyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid t-butyl ester

→

(R)-4-(3-{(S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoylamino}-pyrazol-1-ylmethyl)-2,2-dimethyl-oxazolidin-3-carboxylic acid t-butyl ester

Yield 105.8%

Solvents

dichloromethane

dichloromethane

Conditions

Workup

1. 1
   Washwashed with a saturated ammonium chloride solution, water
2. 2
   Dryinga saturated sodium bicarbonate solution, a saturated sodium chloride solution and dried over magnesium sulfate
3. 3
   OtherThe crude product obtained
4. 4
   Concentrationafter concentration
5. 5
   Otherwas purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 40 g; 0% to 100% ethyl acetate/hexanes)

Procedure

A solution of (S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid (prepared as in Example 64, 0.98 g, 3.01 mmol) in dichloromethane (15 mL) was treated with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride salt (0.64 g, 3.32 mmol), 1-hydroxybenzotriazole (0.45 g, 3.32 mmol) and (R)-4-(3-amino-pyrazol-1-ylmethyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid t-butyl ester (1.07 g, 1.57 mmol). The reaction mixture was stirred for 18 h at 25° C., under nitrogen and then diluted with dichloromethane, washed with a saturated ammonium chloride solution, water, a saturated sodium bicarbonate solution, a saturated sodium chloride solution and dried over magnesium sulfate. The crude product obtained after concentration, was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 40 g; 0% to 100% ethyl acetate/hexanes) to afford (R)-4-(3-{(S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoylamino}-pyrazol-1-ylmethyl)-2,2-dimethyl-oxazolidin-3-carboxylic acid t-butyl ester (1.00 g, 55%) as a white powder: LR-ES-MS m/z calculated for C30H40ClN5O6 [M]+ 601, observed 602 [M+H]+.

Source