Dimethylacetamide → HCID 90373121, compound

HRID 930412Notes

Reaction equation

HRID 930412 reaction equation
[NH2:1][C:2]1[O:3][C@H:4]([C:28]([F:31])([F:30])[F:29])[CH2:5][C@:6]([C:9]2[CH:10]=[C:11]([NH:17][C:18](=[O:27])[C:19]3[C:24]([F:25])=[CH:23][C:22](Cl)=[CH:21][N:20]=3)[CH:12]=[C:13]([F:16])[C:14]=2[F:15])([CH3:8])[N:7]=1.C[C:33]([N:35](C)C)=O>O.CCOC(C)=O.[C-]#N.[Zn+2].[C-]#N.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH2:1][C:2]1[O:3][C@H:4]([C:28]([F:31])([F:30])[F:29])[CH2:5][C@:6]([C:9]2[CH:10]=[C:11]([NH:17][C:18](=[O:27])[C:19]3[C:24]([F:25])=[CH:23][C:22]([C:33]#[N:35])=[CH:21][N:20]=3)[CH:12]=[C:13]([F:16])[C:14]=2[F:15])([CH3:8])[N:7]=1

Participants

7

Reactant 2

HCID 31374DimethylacetamideHCID 90373416HCID 90373416, compound

Product 1

HCID 90373121HCID 90373121, compoundYield 50.7%

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A microwave vial was charged with N-(3-((4S,6S)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4,5-difluorophenyl)-5-chloro-3-fluoropicolinamide (0.182 g, 0.390 mmol), zinc cyanide (0.056 g, 0.468 mmol, Sigma Aldrich), 2-dicyclohexylphosphino-2′,6′-dimethoxy-1′1′-biphenyl (0.032 g, 0.078 mmol, Strem), and tris(dibenzylideneacetone)dipalladium (0) (0.036 g, 0.039 mmol, Strem). The vial was sealed and evacuated/backfilled with nitrogen three times. 1 ml of a premixed 99:1 DMA:water solution was added and the reaction was heated to 120° C. in the microwave for 20 minutes. Upon cooling, the reaction was diluted with water and EtOAc. The organic layer was separated, washed with brine and dried over magnesium sulfate. The crude residue was purified via silica gel flash chromatography using a gradient of 20-100% EtOAc in hexanes) to afford the title compound (0.0904 g, 0.198 mmol, 50.7% yield) as a yellow solid. MS m/z=458.0 [M+H]+. Calculated for C19H13F6N5O2: 457.329.

Workup

  1. customThe vial was sealed and evacuated/backfilled with nitrogen three times
  2. temperatureUpon cooling
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried over magnesium sulfate
  6. customThe crude residue was purified via silica gel flash chromatography

Sources & evidence

ORD record
ord-3be2ae80777b42b998d4bdaf65fe0f3a
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

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