1H-Pyrrolo(2,3-b)pyridine → HCID 66679583, compound

HRID 1678113Notes

Reaction equation

HRID 1678113 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][N:8]=2)[CH:3]=[CH:2]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[C:19]1[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=1>[Cu](I)I.N[C@@H]1CCCC[C@H]1N.O1CCOCC1>[N:21]1[CH:22]=[CH:23][CH:24]=[C:19]([N:1]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][N:8]=3)[CH:3]=[CH:2]2)[CH:20]=1

Participants

7

Reactant 3

HCID 92221H-Pyrrolo(2,3-b)pyridineHCID 122863-BromopyridineHCID 62657Potassium Phosphate, Tribasic

Product 1

HCID 66679583HCID 66679583, compoundYield 108%

Reagents, catalysts & solvents 3

HCID 438061,2-Diaminocyclohexane, trans-CatalystHCID 83717Copper iodideCatalyst2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

To a mixture of 7-azaindole (550 mg, 4.66 mmol), copper iodide (7.4 mg, 0.038 mmol) and potassium phosphate (1.74 g, 8.18 mmol) under a N2 atmosphere is added racemic trans-1,2-diaminocyclohexane (0.046 mL, 0.38 mmol), 3-bromo-pyridine (0.376 mL, 3.9 mmol) followed by anhydrous dioxane (5 mL). The resulting suspension is heated in an oil bath at 110° C. with magnetic stirring for 38 hours. Further copper iodide (65 mg, 0.341 mmol) is added and the resulting mixture heated in an oil bath at 110° C. for 57 hours to give a brown sludgy mixture. Filtration through a short pad of silica gel, washing the cake well with ethyl acetate and evaporation of the filtrate gives the crude product as a dark brown oil. The residue is purified by flash chromatography on a 10-gram silica gel cartridge by elution with heptane:ethyl acetate:dichloromethane (3:1:1, increasing to 32:13:5 and 24:16:10). Fractions containing the product are combined and evaporated to give 818 mg of 1-pyridin-3-yl -7-azaindole as a light brown oil (108% yield). MS: m/e 196 (M+H). 1H NMR (300 MHz, CDCl3): 9.01 (1H, br.s), 8.60 (1H, br.s), 8.39 (1H, dd), 8.30 (1H, d), 8.00 (1H, dd), 7.55 (1H, d), 7.49 (1H, dd), 7.18 (1H, dd), 6.70 (1H, d).

Workup

  1. temperaturethe resulting mixture heated in an oil bath at 110° C. for 57 hours
  2. customto give a brown sludgy mixture
  3. filtrationFiltration through a short pad of silica gel
  4. washwashing the cake
  5. customwell with ethyl acetate and evaporation of the filtrate
  6. customgives the crude product as a dark brown oil
  7. customThe residue is purified by flash chromatography on a 10-gram silica gel cartridge by elution with heptane:ethyl acetate:dichloromethane (3:1:1, increasing to 32:13:5 and 24:16:10)
  8. additionFractions containing the product
  9. customevaporated

Sources & evidence

ORD record
ord-9c7b678326c74c7c957f372880ac8165
Source dataset
uspto-grants-2011_08
Patent number
US08008491B2

Reaction notes

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