Boron trifluoride etherate → Avagacestat

HRID 1803740Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1803740
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]([C@H:24]([CH2:28][CH2:29][C:30]([F:33])([F:32])[F:31])[C:25]([NH2:27])=[O:26])[CH2:12][C:13]2[CH:18]=[CH:17][C:16]([C:19](=[N:21][OH:22])[NH2:20])=[CH:15][C:14]=2[F:23])(=[O:10])=[O:9])=[CH:4][CH:3]=1.[CH:34](OCC)(OCC)OCC.B(F)(F)F.CCOCC.CCOC(C)=O>ClC(Cl)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]3[N:20]=[CH:34][O:22][N:21]=3)=[CH:15][C:14]=2[F:23])[C@H:24]([CH2:28][CH2:29][C:30]([F:32])([F:33])[F:31])[C:25]([NH2:27])=[O:26])(=[O:10])=[O:9])=[CH:4][CH:3]=1

Komponenten

6

Edukt 4

HCID 8000Boron trifluoride etherateHCID 8857Ethyl AcetateHCID 31214Ethyl orthoformateHCID 86630001(R)-2-(4-Chloro-N-(2-fluoro-4-(N'-hydroxycarbamimidoyl)benzyl)-phenylsulfonamido)-5,5,5-trifluoropentanamide

Produkt 1

HCID 46883536AvagacestatAusbeute 69,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 63651,1-DichloroethaneLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

To a solution of (R)-2-(4-chloro-N-(4-cyano-2-fluorobenzyl)phenylsulfonamido)-5,5,5-trifluoropentanamide (6.5 g, 13.6 mmol) in EtOH (70 mL) was added NH2OH (50% in H2O, 2.6 mL 40.8 mmol). The resulting mixture was stirred at 80° C. under nitrogen for 1 h and then cooled to rt. The solvents were evaporated under reduced pressure. The residue was dissolved in EtOAc and washed with water and dried over Na2SO4. Evaporation of the solvent gave a white solid which was recrystallized from EtOAc and hexanes to afford the intermediate amide oxime as a white solid (6.93 g, quantitative yield). To a mixture of the intermediate (R)-2-(4-chloro-N-(2-fluoro-4-(N′-hydroxycarbamimidoyl)benzyl)phenylsulfonamido)-5,5,5-trifluoropentanamide (6.93 g, 13.6 mmol) and triethyl orthoformate (6.77 mL, 40.8 mmol) in dichloroethane (30 mL) was added BF3.OEt2 (0.17 mL, 1.36 mmol). The resulting mixture was stirred at 70° C. for 1 h and then cooled to room temperature. Chromatography (silica gel, biotage, 40+M column, 3% to 80% EtOAc in hexanes, 651 mL) provided the title compound as a white solid. (4.9 g, 69.3% yield).

Aufarbeitung

  1. temperaturecooled to room temperature

Quellen und Nachweise

ORD-Eintrag
ord-10af01695a4847bbb86ee627a20b5c82
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08350084B2

Notizen zur Reaktion

Wird geladen…