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 1626140Notes

Reaction equation

HRID 1626140 reaction equation
[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

Participants

4

Reactant 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

Product 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

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 887MethanolSolvent

Procedure

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]+.

Workup

  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

Sources & evidence

ORD record
ord-751a37249dd1461b8c2f6e4aaf6e0c6a
Source dataset
uspto-grants-2014_07
Patent number
US08785436B2

Reaction notes

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