Dimethylformamide → HCID 24985635, compound

HRID 913403Notes

Reaction equation

HRID 913403 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]2[O:12][C:11]([CH2:13][N:14]3[C:22]4[C:17](=[C:18]([Cl:25])[C:19]([C:23]#[N:24])=[CH:20][CH:21]=4)[CH:16]=[C:15]3[CH:26]([F:28])[F:27])=[N:10][N:9]=2)[CH:5]=[N:6][CH:7]=1.[CH3:29][N:30](C=O)C>[C-]#N.[C-]#N.[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:25][C:18]1[C:19]([C:23]#[N:24])=[CH:20][CH:21]=[C:22]2[C:17]=1[CH:16]=[C:15]([CH:26]([F:28])[F:27])[N:14]2[CH2:13][C:11]1[O:12][C:8]([C:4]2[CH:5]=[N:6][CH:7]=[C:2]([C:29]#[N:30])[CH:3]=2)=[N:9][N:10]=1

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 24985634HCID 24985634, compound

Product 1

HCID 24985635HCID 24985635, compoundYield 61%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst2×

Conditions

Temperature
120 °C

Procedure

To a solution of 1-{[5-(5-bromo-3-pyridinyl)-1,3,4-oxadiazol-2-yl]methyl}-4-chloro-2-(difluoromethyl)-1H-indole-5-carbonitrile (0.015 g, 0.032 mmol) in anhydrous DMF (1.5 mL) under N2, was added Zn(CN)2 (0.002 g, 0.016 mmol) and Pd(PPh3)4 (0.004 g, 0.0032 mmol). The mixture was heated at 120° C., under N2 for 1 h. Additional Pd(PPh3)4 (0.004 g, 0.0032 mmol) was added and the mixture was heated at 120° C., under N2 for another 40 min. Upon cooling, the mixture was partitioned between Et2O and water. The organic phase was washed with water and sat'd brine. The combined aqueous phases were washed with EtOAc. The EtOAc phase was washed with water (2×) and brine. The Et2O and EtOAc phases were combined, dried (Na2SO4) and concentrated in vacuo. The residue was purified by flash chromatography (5-70% EtOAc-hexanes gradient), followed by a second purification by radial chromatography (0-3% MeOH—CH2Cl2 gradient). The product was crystallized from CH2Cl2-hexanes to afford the title compound as a white solid (0.008 g, 61% yield): MS (ES) m/z 411 (M+1).

Workup

  1. temperaturethe mixture was heated at 120° C., under N2 for another 40 min
  2. temperatureUpon cooling
  3. customthe mixture was partitioned between Et2O and water
  4. washThe organic phase was washed with water
  5. washThe combined aqueous phases were washed with EtOAc
  6. washThe EtOAc phase was washed with water (2×) and brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by flash chromatography (5-70% EtOAc-hexanes gradient)
  10. customfollowed by a second purification by radial chromatography (0-3% MeOH—CH2Cl2 gradient)
  11. customThe product was crystallized from CH2Cl2-hexanes

Sources & evidence

ORD record
ord-63f189ee43394841b0b62118481c3d93
Source dataset
uspto-grants-2011_09
Patent number
US08026262B2

Reaction notes

Loading…