Reaktion #1596970

Reaktionsgleichung

(S)-5-tert-butoxy-4-(3-((S)-1-tert-butoxy-6-(3-iodobenzamido)-1-oxohexan-2-yl)ureido)-5-oxopentanoic acid

4-(2-aminoethyl)benzenesulfonamide

HATU

DIPEA

→

(S)-tert-butyl 2-(3-((S)-1-tert-butoxy-1,5-dioxo-5-(4-sulfamoylphenylamino)pentan-2-yl)ureido)-6-(3-iodobenzamido)hexanoate

Lösungsmittel

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe solvents were evaporated under reduced pressure
2. 2
   Sonstigeto give a residue, which
3. 3
   Sonstigewas purified

Vorschrift

A solution of (S)-5-tert-butoxy-4-(3-((S)-1-tert-butoxy-6-(3-iodobenzamido)-1-oxohexan-2-yl)ureido)-5-oxopentanoic acid (212 mg, 0.32 mmol), 4-(2-aminoethyl)benzenesulfonamide (80 mg, 0.40 mmol), HATU (152 mg, 0.40 mmol), and DIPEA (0.50 mL) in DMF (5 mL) was stirred at 50° C. overnight. The solvents were evaporated under reduced pressure to give a residue, which was purified utilizing a Biotage SP4 with a gradient of 10-100% EtOAc in hexane to give (S)-tert-butyl 2-(3-((S)-1-tert-butoxy-1,5-dioxo-5-(4-sulfamoylphenylamino)pentan-2-yl)ureido)-6-(3-iodobenzamido)hexanoate. A solution of the above product was dissolved in TFA (2.0 mL)/DCM (2.0 mL) and stirred at room temperature for 3 h. The solvents were removed under reduced pressure to give a residue, which was purified by Amberchrom™ to give ((S)-2-(3-((S)-1-carboxy-4-oxo-4-(4-sulfamoylphenethylamino)butyl)ureido)-6-(3-iodobenzamido)hexanoic acid (40 mg, 17% over 2 steps) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 8.54 (t, J=5.4 Hz, 1H), 8.17 (s, 1H), 7.97 (t, J=5.4 Hz, 1H), 7.86 (d, J=8.0 Hz, 1H), 7.83 (d, J=8.0 Hz, 1H), 7.72 (d, J=8.4 Hz, 2H), 7.37 (d, J=8.0 Hz, 2H), 7.28-7.23 (m, 3H), 6.32 (t, J=7.0 Hz, 2H), 4.07-3.99 (m, 2 H), 3.27-2.80 (m, 2H), 2.75 (t, J=7.2 Hz, 2H), 2.10-1.29 (m, 10H); ESMS m/z: 732.2 (M+H)+. Synthesis of Exemplary Formula IV Compounds

Quelle