Pyrrole → HCID 44465602, compound

HRID 383446Notes

Reaction equation

HRID 383446 reaction equation
Br[C:2]1[N:3]([C:13]2[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=2)[C:4]2[C:9]([C:10]=1[C:11]#[N:12])=[CH:8][CH:7]=[CH:6][CH:5]=2.[NH:20]1[CH:24]=[CH:23][CH:22]=[CH:21]1.C(=O)([O-])[O-].[Cs+].[Cs+]>[Cu]I.CN(C=O)C>[OH:19][C:16]1[CH:17]=[CH:18][C:13]([N:3]2[C:4]3[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=3)[C:10]([C:11]#[N:12])=[C:2]2[N:20]2[CH:24]=[CH:23][CH:22]=[CH:21]2)=[CH:14][CH:15]=1

Participants

6

Reactant 3

HCID 8027PyrroleHCID 10796Cesium carbonateHCID 44241532HCID 44241532, compound

Product 1

HCID 44465602HCID 44465602, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

2-Bromo-1-(4-hydroxy-phenyl)-1H-indole-3-carbonitrile (Example 1), 1.4 eq pyrrole, 2 eq cesium carbonate and 20 mol % copper(I) iodide was mixed in a oven-dried vial, DMF was added and the mixture was flushed with nitrogen. The vial was sealed and stirred at 120° C. for 48 hours. The reaction-mixture was cooled to rt, diluted with EtOAc and filtered through silica. The crude mixture was evaporated to dryness and subjected to reversed phase preparative HPLC. Appropriate fractions were combined and evaporated, and identified by 1H-NMR and LC/MS. Purity was determined by analytical HPLC. ES/MS m/z: 300.2 (M+H), 298.3 (M−H); 1H NMR (acetone-d6, 500 MHz): 7.74 (m, 1H), 7.41-7.35 (m, 2H), 7.27 (m, 214), 7.23 (m, 1H), 6.98 (m, 214), 6.95 (t, 2H, J=2.2 Hz) and 6.23 (t, 2H, J=2.2 Hz).

Workup

  1. additionwas added
  2. customthe mixture was flushed with nitrogen
  3. customThe vial was sealed
  4. temperatureThe reaction-mixture was cooled to rt
  5. additiondiluted with EtOAc
  6. filtrationfiltered through silica
  7. customThe crude mixture was evaporated to dryness
  8. customevaporated

Sources & evidence

ORD record
ord-013e9e6b9cc44569b3bf6d476674aff0
Source dataset
uspto-grants-2013_02
Patent number
US08367665B2

Reaction notes

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