2-[4-((R)-2-amino-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-4-yl)-5-fluoro-2-nitro-phenoxy]-1-(5-chloro-pyridin-2-yl)-ethanone → (R)-4-[(RS)-3-(5-chloro-pyridin-2-yl)-7-fluoro-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl]-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine

HRID 1626140Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1626140
[NH2:1][C:2]1[O:3][CH2:4][C:5]([F:31])([F:30])[C@:6]([C:9]2[C:25]([F:26])=[CH:24][C:12]([O:13][CH2:14][C:15]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][N:18]=3)=O)=[C:11]([N+:27]([O-])=O)[CH:10]=2)([CH3:8])[N:7]=1>[Ni].CO>[Cl:23][C:20]1[CH:21]=[CH:22][C:17]([CH:15]2[NH:27][C:11]3[CH:10]=[C:9]([C@:6]4([CH3:8])[C:5]([F:31])([F:30])[CH2:4][O:3][C:2]([NH2:1])=[N:7]4)[C:25]([F:26])=[CH:24][C:12]=3[O:13][CH2:14]2)=[N:18][CH:19]=1

Komponenten

4

Edukt 1

HCID 710089012-[4-((R)-2-amino-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-4-yl)-5-fluoro-2-nitro-phenoxy]-1-(5-chloro-pyridin-2-yl)-ethanone

Produkt 1

HCID 71008632(R)-4-[(RS)-3-(5-chloro-pyridin-2-yl)-7-fluoro-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl]-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 935NickelKatalysatorHCID 887MethanolLösungsmittel

Versuchsvorschrift

A dispersion of 2-[4-((R)-2-amino-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-4-yl)-5-fluoro-2-nitro-phenoxy]-1-(5-chloro-pyridin-2-yl)-ethanone (160 mg, 349 μmol) and Raney Nickel (30 mg) in methanol (22 ml) was hydrogenated. For the workup, the reaction mixture was filtered through glass fiber paper and the solution was evaporated at reduced pressure. The crude product was purified by flash chromatography on a silica-NH2 phase using a gradient of heptane/ethyl acetate=100:0 to 0 to 100 as the eluent. The (R)-4-[(RS)-3-(5-chloro-pyridin-2-yl)-7-fluoro-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl]-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine was obtained as a red solid. MS (ISP): m/z=413.2 [M+H]+.

Aufarbeitung

  1. filtrationFor the workup, the reaction mixture was filtered through glass fiber paper
  2. customthe solution was evaporated at reduced pressure
  3. customThe crude product was purified by flash chromatography on a silica-NH2 phase

Quellen und Nachweise

ORD-Eintrag
ord-751a37249dd1461b8c2f6e4aaf6e0c6a
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08785436B2

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