Indole → HCID 59004598, compound

HRID 1668468Notes

Reaction equation

HRID 1668468 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([NH2:8])=[N:6][CH:7]=1.[O-:9]P([O-])([O-])=O.[K+].[K+].[K+].CN[CH2:19][CH2:20][NH:21][CH3:22].[NH:23]1[C:31]2[C:26](=CC=C[CH:30]=2)[CH:25]=[CH:24]1.BrC1C=NC=CC=1.[OH2:39]>C1(C)C=CC=CC=1.[Cu](I)I>[N+:23]([C:31]1[CH:26]=[C:25]2[C:20](=[CH:19][CH:30]=1)[N:21]([C:2]1[CH:3]=[CH:4][C:5]([NH2:8])=[N:6][CH:7]=1)[CH:22]=[CH:24]2)([O-:9])=[O:39]

Participants

9

Reactant 6

HCID 798IndoleHCID 962WaterHCID 8070N,N'-Dimethylethylenediamine2×HCID 122863-BromopyridineHCID 62657Potassium Phosphate, TribasicHCID 706222-Amino-5-bromopyridine

Product 1

HCID 59004598HCID 59004598, compoundYield 36.1%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalyst2×HCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A suspension of compound 1 (195 mg, 1.20 mmol), 5-bromopyridin-2-amine (173 mg, 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 the desired compound 75 (110 mg, 36.1%). 1H NMR (DMSO-d6) δ 8.65 (d, J=2.2 Hz, 1H), 8.10 (d, J=2.7 Hz, 1H), 8.05 (dd, J=2.7, 6.9 Hz, 1H), 7.76 (d, J=3.2 Hz, 1H), 7.60 (dd, J=2.9, 6.0 Hz, 1H), 7.47 (d, J=9.2 Hz, 1H), 6.94 (d, J=3.2 Hz, 1H), 6.61 (d, J=8.8 Hz, 1H); ESI-MS (m/z, %): 255 (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-1155f7bd18b84f99b4b0bf55c2fea5cb
Source dataset
uspto-grants-2011_08
Patent number
US07989447B2

Reaction notes

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