Reaktion #49233

Reaktionsgleichung

3-(((1S,2S)-1-((2R,4R)-1-(tert-butoxycarbonyl)-4-propoxypyrrolidin-2-yl)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)propan-2-yl)carbamoyl)benzoic acid

HATU

N-methylbutan-1-amine

( A )

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

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

→

title compound

Ausbeute 80.0%

N1-butyl-N3-((1R,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1-((2R,4R)-4-propoxypyrrolidin-2-yl)propan-2-yl)-N1-methylisophthalamide

Ausbeute 80.0%

Lösungsmittel

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe crude mixture was purified by silica gel Flash Chromatography (0% to 20% to 40% to 60% to 80% EtOAc/Hexane step gradient)

Vorschrift

Step 3 (A): Preparation of (2R,4R)-tert-butyl 2-((1S,2S)-1-(tert-butyldimethylsilyloxy)-2-(3-(carbamoyl)benzamido)-3-(3,5-difluorophenyl)propyl)-4-propoxypyrrolidine-1-carboxylate. To a solution of 3-(((1S,2S)-1-((2R,4R)-1-(tert-butoxycarbonyl)-4-propoxypyrrolidin-2-yl)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)propan-2-yl)carbamoyl)benzoic acid (Step 1 (C), 66 mg, 0.10 mmol) in dichloromethane (2 mL) were added HATU (46 mg, 0.12 mmol) and N-methylbutan-1-amine (12 mg, 0.13 mmol) and the reaction mixture was stirred at rt overnight. The crude mixture was purified by silica gel Flash Chromatography (0% to 20% to 40% to 60% to 80% EtOAc/Hexane step gradient) to give 60 mg of the title compound (80% yield): 1H NMR (CDCl3, 500 MHz) δ 0.02 (3H, s), 0.05 (3H, s), 0.75 (2H, m), 0.83 (9H, s), 0.88 (3H, m), 0.93-0.96 (2H, m), 1.12 (1H, m), 1.35-1.41 (1H, m), 1.48-1.53 (11H, m), 1.61 (1H, m), 2.01-2.06 (1H, m), 2.19 (1H, d, J=10 Hz), 2.66 (1H, m), 2.89-2.93 (3H, m), 3.04 (1H, s), 3.21 (1H, brd s), 3.27-3.36 (3H, m), 3.51 (1H, brd s), 3.75 (1H, dd, J=5, 15 Hz), 3.97 (1H, m), 4.05-4.11 (2H, m), 4.60 (1H, m), 6.59 (1H, m), 6.76 (2H, d, J=5 Hz), 7.41-7.48 (2H, m), 7.87 (2H, s), 8.13 (1H, brd s). MS (ESI) (M+H)+ 746.36.

Quelle