Reaktion #49246

Reaktionsgleichung

(2R,4R)-tert-butyl 2-((1S,2S)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)-2-(3-hydroxy-5-(2-oxopyrrolidin-1-yl)benzamido)propyl)-4-propoxypyrrolidine-1-carboxylate

cesium carbonate

2-iodopropane

( A )

(2R,4R)-tert-butyl 2-((1S,2S)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)-2-(3-((R)-2-(methoxymethyl)pyrrolidine-1-carbonyl)-5-(oxazol-2-yl)benzamido)propyl)-4-propoxypyrrolidine-1-carboxylate

(2R,4R)-tert-butyl 2-((1S,2S)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)-2-(3-isopropoxy-5-(2-oxopyrrolidin-1-yl)benzamido) propyl)-4-propoxypyrrolidine-1-carboxylate

→

title compound

N-((1R,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1-((2R,4R)-4-propoxypyrrolidin-2-yl)propan-2-yl)-3-isopropoxy-5-(2-oxopyrrolidin-1-yl)benzamide

Lösungsmittel

DMF

Ethyl acetate

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigethe reaction mixture was microwaved at 60° C. for 2 h
2. 2
   Waschenthe mixture was washed with Brine, H2O
3. 3
   Einengenconcentrated under vacuum
4. 4
   SonstigeThe crude mixture was purified by silica gel Flash Chromatography (0% to 20% to 30% to 40% EtOAc/Hexane step gradient)

Vorschrift

Step 14 (A): (2R,4R)-tert-butyl 2-((1S,2S)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)-2-(3-isopropoxy-5-(2-oxopyrrolidin-1-yl)benzamido) propyl)-4-propoxypyrrolidine-1-carboxylate. To a solution of (2R,4R)-tert-butyl 2-((1S,2S)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)-2-(3-hydroxy-5-(2-oxopyrrolidin-1-yl)benzamido)propyl)-4-propoxypyrrolidine-1-carboxylate (Preparation I, 38 mg, 0.05 mmol) in DMF (1 mL) were added cesium carbonate (29 mg, 0.09 mmol) and 2-iodopropane (42 mg, 0.25 mmol) and the reaction mixture was microwaved at 60° C. for 2 h. Ethyl acetate (100 mL) was added and the mixture was washed with Brine, H2O and concentrated under vacuum. The crude mixture was purified by silica gel Flash Chromatography (0% to 20% to 30% to 40% EtOAc/Hexane step gradient) to give 21 mg of the title compound: 1H NMR (CDCl3, 500 MHz) δ ppm 0.01 (3H, s), 0.07 (3H, s), 0.86 (9H, s), 0.88 (3H, m), 1.32 (6H, d, J=5 Hz), 1.46-1.54 (11H, m), 2.03-2.21 (4H, m), 2.59 (2H, m), 2.62 (1H, dd, J=10, 15 Hz), 2.94 (1H, m), 3.26-3.36 (3H, m), 3.76 (1H, dd, J=5, 10 Hz), 3.84-3.91 (2H, m), 3.97 (1H, m), 4.04-4.07 (1H, m), 4.11-4.13 (1H, m), 4.55 (1H, m), 4.63 (1H, m), 6.59 (1H, m), 6.78 (2H, d, J=5 Hz), 7.20 (1H, s), 7.33 (1H, s), 7.71 (1H, s), 7.99 (1H, d, J=10 Hz). MS (ESI) (M+H)+ 775.45.

Quelle