Reaktion #158840

ord-37dbbb980e384507b150930d32e3f1f8

Reaktionsgleichung

CCCc1cc(C(=O)O)nn1Cc1ccc(-c2ccccc2S(=O)(=O)NC(C)=O)cc1
1-(2′-acetylsulfamoylbiphenyl-4-ylmethyl)-5-propyl-1H-pyrazole-3-carboxylic acid
CN(C)C(On1nnc2cccnc21)=[N+](C)C.F[P-](F)(F)(F)(F)F
HATU
CCN(C(C)C)C(C)C
DIPEA
CN(C)C=O
DMF
N[C@H](Cc1ccccc1)[C@@H](O)C(=O)O
(2R,3R)-3-amino-2-hydroxy-4-phenylbutyric acid
→
CCCc1cc(C(=O)N[C@H](Cc2ccccc2)[C@@H](O)C(=O)O)nn1Cc1ccc(-c2ccccc2S(=O)(=O)NC(C)=O)cc1
title compound
Ausbeute 97.0%
CCCc1cc(C(=O)N[C@H](Cc2ccccc2)[C@@H](O)C(=O)O)nn1Cc1ccc(-c2ccccc2S(=O)(=O)NC(C)=O)cc1
(2R,3R)-3-(1-((2′-(N-Acetylsulfamoyl)biphenyl-4-yl)methyl)-5-propyl-1H-pyrazole-3-carboxamido)-2-hydroxy-4-phenylbutanoic Acid
Ausbeute 97.0%

Edukte

CCCc1cc(C(=O)O)nn1Cc1ccc(-c2ccccc2S(=O)(=O)NC(C)=O)cc1
1-(2′-acetylsulfamoylbiphenyl-4-ylmethyl)-5-propyl-1H-pyrazole-3-carboxylic acid
CN(C)C(On1nnc2cccnc21)=[N+](C)C.F[P-](F)(F)(F)(F)F
HATU
CCN(C(C)C)C(C)C
DIPEA
CN(C)C=O
DMF
N[C@H](Cc1ccccc1)[C@@H](O)C(=O)O
(2R,3R)-3-amino-2-hydroxy-4-phenylbutyric acid

Reagenzien

Keine

Reaktionsbedingungen

Temperatur
45°CELSIUS
Detaillierte Bedingungen
See reaction.notes.procedure_details.

Aufarbeitung

  1. 1
    EinengenThe mixture was concentrated
  2. 2
    workup.DISSOLUTIONre-dissolved in water/MeCN/TFA
  3. 3
    Sonstigepurified

Vorschrift

A solution of 1-(2′-acetylsulfamoylbiphenyl-4-ylmethyl)-5-propyl-1H-pyrazole-3-carboxylic acid (250 mg, 570 μmol), HATU (215 mg, 566 μmol) and DIPEA (592 μL, 3.4 mmol) in DMF (18 mL, 230 mmol) was stirred to pre-activate the acid. After 15 minutes, (2R,3R)-3-amino-2-hydroxy-4-phenylbutyric acid (110 mg, 566 μmol) was added. The resulting solution was stirred at 45° C. overnight. The mixture was concentrated, re-dissolved in water/MeCN/TFA and purified using reverse phase liquid chromatography to yield the title compound (197 mg, 97% purity). MS m/z: [M+H]+ calcd for C32H34N4O7S, 619.22. found 619.6.

Quelle

DOI: 10.6084/m9.figshare.5104873.v1Patent: US08822522B2uspto-grants-2014_09