Dimethylformamide → HCID 57800229, compound

HRID 913398Notes

Reaction equation

HRID 913398 reaction equation
FC(F)(F)S(O[C:7]1[C:8]([Cl:28])=[C:9]2[C:13](=[CH:14][CH:15]=1)[N:12]([S:16]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)(=[O:18])=[O:17])[C:11]([CH:25]([F:27])[F:26])=[CH:10]2)(=O)=O.[CH3:31][N:32](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:28][C:8]1[C:7]([C:31]#[N:32])=[CH:15][CH:14]=[C:13]2[C:9]=1[CH:10]=[C:11]([CH:25]([F:26])[F:27])[N:12]2[S:16]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)(=[O:17])=[O:18]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 57800190HCID 57800190, compound

Product 1

HCID 57800229HCID 57800229, compoundYield 62%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
120 °C

Procedure

To a solution of 4-chloro-2-(difluoromethyl)-1-(phenylsulfonyl)-1H-indol-5-yl trifluoromethanesulfonate (0.75 g, 1.53 mmol) in anhydrous DMF (10 mL) under N2, was added Zn(CN)2 (0.093 g, 0.80 mmol) and Pd(PPh3)4 (0.088 g, 0.077 mmol) and the resulting mixture was heated at 120° C. for 2 h. Upon cooling, the mixture was partitioned between Et2O and water. The organic phase was washed with water. The combined aqueous phases were reextracted with Et2O. The combined organic phases were washed with sat'd brine, dried (Na2SO4) and concentrated in vacuo. The residue was purified by flash chromatography (0-40% EtOAc-hexanes gradient) to afford 4-chloro-2-(difluoromethyl)-1-(phenylsulfonyl)-1H-indole-5-carbonitrile (0.35 g, 62% yield) 1H NMR (400 MHz, CDCl3) δ 8.11 (d, J=8.8 Hz, 1H), 7.94 (d, J=7.8 Hz, 2H), 7.67-7.63 (m, 2H), 7.52 (t, J=7.8 Hz, 2H), 7.35 (t, J=54 Hz, 1H), 7.25 (s, 1H, overlapping CHCl3 signal); MS (ES) m/z 365 (M−1)) and 2-(difluoromethyl)-1-(phenylsulfonyl)-1H-indole-4,5-dicarbonitrile (0.054 g, 10% yield) (1H NMR (400 MHz, CDCl3) δ 8.45 (d, J=8.8 Hz, 1H), 7.96 (d, J=7.8 Hz, 2H), 7.77 (d, J=8.8 Hz, 1H), 7.68 (t, J=7.6 Hz, 1H), 7.55 (t, J=7.8 Hz, 2H), 7.38 (t, J=54 Hz, 1H), 7.35 (s, 1H); MS (ES) m/z 356 (M−1)).

Workup

  1. temperatureUpon cooling
  2. customthe mixture was partitioned between Et2O and water
  3. washThe organic phase was washed with water
  4. washThe combined organic phases were washed with sat'd brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography (0-40% EtOAc-hexanes gradient)

Sources & evidence

ORD record
ord-374d12c682fa4d2fad0d651ccce48774
Source dataset
uspto-grants-2011_09
Patent number
US08026262B2

Reaction notes

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