Dimethylformamide → HCID 66609499, compound

HRID 473146Notes

Reaction equation

HRID 473146 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([C:6]([S:22][CH3:23])=[N:7][C:8]([C:12]([F:21])([F:20])[C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][N:14]=3)=[N:9]2)=[CH:4][CH:3]=1.[CH3:24][N:25](C=O)C>C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].[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]>[F:20][C:12]([F:21])([C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][N:14]=1)[C:8]1[N:7]=[C:6]([S:22][CH3:23])[C:5]2[C:10](=[CH:11][C:2]([C:24]#[N:25])=[CH:3][CH:4]=2)[N:9]=1

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 66609624HCID 66609624, compound

Product 1

HCID 66609499HCID 66609499, compoundYield 79%

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
90 °C

Procedure

To a mixture of 1,1′-bis(diphenylphosphino)ferrocene (25 mg, 0.045 mmol), zinc cyanide (55 mg, 0.47 mmol), and 7-bromo-2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazoline from Example 7 Step E (150 mg, 0.376) was added tris(dibenzylideneacetone)dipalladium (34 mg, 0.031 mmol) in DMF (3 mL). The reaction vessel was evacuated, and flushed with argon (2×), then the mixture was heated at 90° C. overnight during which time most of the solvent evaporated. The mixture was diluted with EtOAc (20 mL) and washed with water (20 mL), 2N NH4OH (20 mL), and brine, dried over Na2SO4, and concentrated under reduced pressure onto Celite. The mixture was purified by silica gel chromatography eluting with a 10-60% EtOAc/hexanes to afford 2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazoline-7-carbonitrile as a solid (0.103 g, 79%). LC-MS (ESI) m/z 347 (M+H)+

Workup

  1. customThe reaction vessel was evacuated
  2. customflushed with argon (2×)
  3. customevaporated
  4. additionThe mixture was diluted with EtOAc (20 mL)
  5. washwashed with water (20 mL), 2N NH4OH (20 mL), and brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under reduced pressure onto Celite
  8. customThe mixture was purified by silica gel chromatography
  9. washeluting with a 10-60% EtOAc/hexanes

Sources & evidence

ORD record
ord-4ca22de371bd4e6eb6b013b13a03e11f
Source dataset
uspto-grants-2014_01
Patent number
US08633207B2

Reaction notes

Loading…