Ammonia → HCID 24985459, compound

HRID 913389Notes

Reaction equation

HRID 913389 reaction equation
[Cl:1][C:2]1[C:10]([C:11]#[N:12])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([C:18]([OH:20])=O)[N:6]2[CH2:13][C:14]([F:17])([F:16])[F:15].S(Cl)(Cl)=O.C[N:26](C=O)C.N>C1(C)C=CC=CC=1.CO>[Cl:1][C:2]1[C:10]([C:11]#[N:12])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([C:18]([NH2:26])=[O:20])[N:6]2[CH2:13][C:14]([F:17])([F:16])[F:15]

Participants

7

Reactant 4

HCID 222AmmoniaHCID 6228DimethylformamideHCID 24386Thionyl Chloride2×HCID 57800167HCID 57800167, compound

Product 1

HCID 24985459HCID 24985459, compoundYield 65%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
60 °C

Procedure

To a suspension of 4-chloro-5-cyano-1-(2,2,2-trifluoroethyl)-1H-indole-2-carboxylic acid (0.026 g, 0.086 mmol) in toluene (3 mL) was added thionyl chloride (0.01 g, 0.09 mmol) and a catalytic amount of DMF. The mixture was heated at 60° C. The reaction was followed by TLC at 30 min intervals, and additional thionyl chloride was added accordingly (an additional 0.082 g, 0.68 mmol was added). Upon cooling, a solution of NH3 in MeOH (2M, 5 mL) was added and the mixture was stirred rapidly for 5 min. The mixture was concentrated in vacuo and the residue was partitioned between EtOAc and water. The organic phase was washed with sat'd brine, dried (Na2SO4) and concentrated in vacuo. The residue was purified by flash chromatography (10-80% EtOAc-hexanes gradient) and the product was crystallized from CH2Cl2-MeOH-hexanes to afford the title compound as a white solid (0.017 g, 65% yield): MS (ES) m/z 302 (M+1).

Workup

  1. additionwas added)
  2. temperatureUpon cooling
  3. concentrationThe mixture was concentrated in vacuo
  4. customthe residue was partitioned between EtOAc and water
  5. washThe organic phase was washed with sat'd brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography (10-80% EtOAc-hexanes gradient)
  9. customthe product was crystallized from CH2Cl2-MeOH-hexanes

Sources & evidence

ORD record
ord-dd086d0576ed4f25a42d0a175983a44f
Source dataset
uspto-grants-2011_09
Patent number
US08026262B2

Reaction notes

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