Reaktion #47692

Reaktionsgleichung

2-t-butoxycarbonylamino-3-(tetrahydropyran-4-yl)-propionic acid

1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol

(S)-2-[4-(2,3-dichloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-amide hydrochloride

N,N-diisopropylethylamine

benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate

→

[1-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-ylcarbamoyl]-2-(tetrahydro-pyran-4-yl)-ethyl]-carbamic acid t-butyl ester

Ausbeute 82.0%

Lösungsmittel

N,N-dimethylformamide

Reaktionsbedingungen

Aufarbeitung

1. 1
   EinengenAt this time the mixture was concentrated in vacuo
2. 2
   Sonstigethe residue partitioned between ethyl acetate
3. 3
   SonstigeThe layers were separated
4. 4
   Waschenthe organic layer was washed with water and brine
5. 5
   Trocknendried over anhydrous sodium sulfate
6. 6
   FiltrationThe mixture was filtered
7. 7
   Einengenconcentrated in vacuo
8. 8
   Sonstigethe residue purified by ISCO flash chromatography (RediSep silica 120 g, 30% to 100% ethyl acetate/hexanes) which

Vorschrift

A solution of 2-t-butoxycarbonylamino-3-(tetrahydropyran-4-yl)-propionic acid (2.61 g, 9.55 mmol) and 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in U.S. Pat. Appl. US2008021032 Example 80, 1.8 g, 11.6 mmol) in N,N-dimethylformamide (15 mL) was treated with N,N-diisopropylethylamine (2.58 g, 20 mmol) and benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (8.84 g, 20 mmol) and the resulting mixture stirred at room temperature for 12 h. At this time the mixture was concentrated in vacuo and the residue partitioned between ethyl acetate and a concentrated ammonium chloride solution. The layers were separated and the organic layer was washed with water and brine, and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated in vacuo and the residue purified by ISCO flash chromatography (RediSep silica 120 g, 30% to 100% ethyl acetate/hexanes) which afforded [1-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-ylcarbamoyl]-2-(tetrahydro-pyran-4-yl)-ethyl]-carbamic acid t-butyl ester (3.2 g, 82%) as a white solid.

Quelle