Reaktion #49249

Reaktionsgleichung

( B )

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

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

(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

→

title compound

N1-((1R,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1-((2R,4R)-4-propoxypyrrolidin-2-yl)propan-2-yl)-N3-(1-(4-fluorophenyl)ethyl)isophthalamide

Lösungsmittel

HCl

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe solvent was removed
2. 2
   Sonstigethe mixture was purified by reverse phase HPLC (30×100 mm PHENOMENEX-LUNA S5 column, 34-90% methanol/H2O/0.1% TFA)

Vorschrift

Step 16 (B): N1-((1R,2 S)-3-(3,5-Difluorophenyl)-1-hydroxy-1-((2R,4R)-4-propoxypyrrolidin-2-yl)propran-2-yl)-N3-(1-(4-fluorophenyl)ethyl)isophthalamide. The solution of (2R,4R)-tert-butyl 2-((1S,2S)-1-(tert-butyldimethylsilyoxy)-2-(3-(carbonyl)benzamido)-3-(3,5-difluorophenyl)propyl)-4-propoxypyrrolidine-1-carboxylate (Step 16 (A), 38 mg) in HCl (4.0 M solution in dioxane, 1 mL) was added 2 drops of H2O and the mixture was stirred at rt for 1 h. The solvent was removed and the mixture was purified by reverse phase HPLC (30×100 mm PHENOMENEX-LUNA S5 column, 34-90% methanol/H2O/0.1% TFA) to give 30 mg of the title compound: 1H NMR (CD3OD, 500 MHz) δ ppm 0.97 (3H, m), 1.58 (3H, d, J=5 Hz), 1.62 (2H, m), 2.17 (1H, m), 2.50 (1H, m), 2.86 (1H, m), 3.34-3.49 (5H, m), 3.81 (1H, m), 4.06 (1H, dd, J=5, 10 Hz), 4.22-4.25 (2H, m), 5.21-5.27 (1H, m), 6.73 (1H, m), 6.89-6.90 (2H, m), 7.07 (2H, m), 7.41-7.44 (2H, m), 7.53 (1H, t, J=10 Hz), 7.79-7.82 (1H, m), 7.96 (1H, m), 8.12-8.14 (1H, m), MS (ESI) (M+H)+ 584.32.

Quelle