Indole → HCID 18005067, compound

HRID 1668465Notes

Reaction equation

HRID 1668465 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.[O-:8]P([O-])([O-])=O.[K+].[K+].[K+].CN[CH2:18][CH2:19][NH:20][CH3:21].[NH:22]1[C:30]2[C:25](=CC=C[CH:29]=2)[CH:24]=[CH:23]1.[OH2:31]>C1(C)C=CC=CC=1.[Cu](I)I>[N+:22]([C:30]1[CH:25]=[C:24]2[C:19](=[CH:18][CH:29]=1)[N:20]([C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1)[CH:21]=[CH:23]2)([O-:8])=[O:31]

Participants

8

Reactant 5

HCID 798IndoleHCID 962WaterHCID 8070N,N'-Dimethylethylenediamine2×HCID 122863-Bromopyridine2×HCID 62657Potassium Phosphate, Tribasic

Product 1

HCID 18005067HCID 18005067, compoundYield 67.9%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalyst2×HCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A suspension of compound 1 (195 mg, 1.20 mmol), 3-Bromopyridine (98 μL, 1.00 mmol), copper iodide (9.5 mg, 0.05 mmol) and K3PO4 (400 mg, 2.10 mmol) in toluene (6 mL) was treated with N,N′-dimethylethylenediamine (21.5 μL, 0.20 mmol) then heated at 110° C. overnight. A TLC analysis indicated mostly starting indole and 3-bromopyridine and a new more polar spot. The reaction mixture was treated with additional copper iodide ((9.5 mg, 0.05 mmol) and N,N′-dimethylethylenediamine (21.5 μL, 0.20 mmol). The mixture was heated at 110° C. for 7 hours. After cooling, the mixture was poured into H2O (20 mL) then extracted with CH2Cl2 (100 mL). The organic layer was separated, washed with brine and concentrated to give a yellow solid which was subjected to flash chromatography on silica gel (CH2Cl2 to MeOH:CH2Cl2, 5:95) to give compound 72 (195 mg, 67.9%) as a yellow solid. 1H NMR (DMSO-d6) δ 8.90 (d, J=2.4 Hz, 1H), 8.70-8.69 (m, 2H), 8.16-8.07 (m, 2H), 7.99 (d, J=3.2 Hz, 1H), 7.71-7.65 (m, 2H), 7.05 (d, J=3.3 Hz); ESI-MS (m/z, %): 240 (M+1, 100%).

Workup

  1. temperatureThe mixture was heated at 110° C. for 7 hours
  2. temperatureAfter cooling
  3. extractionthen extracted with CH2Cl2 (100 mL)
  4. customThe organic layer was separated
  5. washwashed with brine
  6. concentrationconcentrated
  7. customto give a yellow solid which

Sources & evidence

ORD record
ord-4f849f1d3387499faecd3dfcc313eb75
Source dataset
uspto-grants-2011_08
Patent number
US07989447B2

Reaction notes

Loading…