Potassium Carbonate → 6-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-isoquinoline

HRID 751310Notes

Reaction equation

HRID 751310 reaction equation
I[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[N:7][CH:6]=[CH:5]2.[CH3:12][C:13]1[N:18]=[C:17]([C:19]2[C:20](B(O)O)=[C:21]3[CH2:26][CH2:25][CH2:24][N:22]3[N:23]=2)[CH:16]=[CH:15][CH:14]=1.C(=O)([O-])[O-].[K+].[K+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCOCC1>[CH3:12][C:13]1[N:18]=[C:17]([C:19]2[C:20]([C:2]3[CH:3]=[C:4]4[C:9](=[CH:10][CH:11]=3)[CH:8]=[N:7][CH:6]=[CH:5]4)=[C:21]3[CH2:26][CH2:25][CH2:24][N:22]3[N:23]=2)[CH:16]=[CH:15][CH:14]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 126795216-IodoisoquinolineHCID 247701172-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-3-boronic acid

Product 1

HCID 100420546-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-isoquinolineYield 51.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Dissolve 6-iodoisoquinoline (0.085 g, 0.333 mmol) and 2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-3-boronic acid (Preparation 2; 0.077 g, 0.317 mmol) in dioxane (2.5 mL). Add 5M aqueous potassium carbonate (0.667 mL, 3.33 mmol) followed by triphenylphosphine (5.2 g, 0.020 mmol) and tris(dibenzylidineacetone)dipalladium (18 mg, 0.020 mmol). Reflux the mixture for 2 h and cool to room temperature. Load the reaction mixture on to a cartridge containing SCX resin (5 g) and wash the resin sequentially with 1 volume dichloromethane, 1 volume methanol, and 1 volume methanol containing 2N ammonia. Remove the organic solvents under reduced pressure. Chromatograph on 15 g silica gel eluting with 5% methanol in ethyl acetate to provide 0.053 g (48%) of the title compound as a tan solid.

Workup

  1. temperatureReflux the mixture for 2 h
  2. washwash the resin sequentially with 1 volume dichloromethane, 1 volume methanol, and 1 volume methanol containing 2N ammonia
  3. customRemove the organic solvents under reduced pressure

Sources & evidence

ORD record
ord-3704162c19d84bb5bea7fa864e624cbe
Source dataset
uspto-grants-2008_07
Patent number
US07405299B2

Reaction notes

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