Methanol → HCID 53629193, compound

HRID 1924324Notes

Reaction equation

HRID 1924324 reaction equation
Br[C:2]1[C:3]([CH2:20][OH:21])=[C:4]2[N:10]=[CH:9][N:8]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=3)[C:5]2=[N:6][CH:7]=1.CO.[C:24]1(B(O)O)[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)CC.O.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:19][O:18][C:15]1[CH:16]=[CH:17][C:12]([CH2:11][N:8]2[C:5]3=[N:6][CH:7]=[C:2]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[C:3]([CH2:20][OH:21])=[C:4]3[N:10]=[CH:9]2)=[CH:13][CH:14]=1

Participants

9

Reactant 4

HCID 887MethanolHCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 57742987HCID 57742987, compound

Product 1

HCID 53629193HCID 53629193, compoundYield 85%

Reagents, catalysts & solvents 4

HCID 74236Tetrabutylammonium BromideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 7854PropionitrileSolvent

Conditions

Temperature
110 °C

Procedure

A reactor containing [6-bromo-3-(4-methoxybenzyl)-3H-imidazo[4,5-b]pyridin-7-yl]methanol x211 (0.55 g, 1.58 mmol) in propionitrile (4 ml) and methanol (1 ml) is charged sequentially with phenylboronic acid (0.24 g, 1.25 eq, 1.98 mmol), sodium carbonate (0.34 g) in water (1.6 ml, 2 eq as a 2 M aqueous solution, 3.16 mmol), and tetrabutylammonium bromide (0.1 g, 0.2 eq, 0.32 mmol). The content of the reactor is evacuated several times and subsequently flushed with argon. Then tetrakis(triphenylphosphine)palladium(0) (0.09 g, 5 mol %, 0.08 mmol) is added. The reactor is equipped with a reflux condenser. The whole apparatus is evacuated twice and subsequently flushed with argon. The reaction mixture is kept for 26 h in a flow of argon under vigorous stirring at a bath temperature of 110° C. In the process, the strongly heterogeneous reaction mixture transforms into a solution. When the reaction is complete, the obtained solution is partitioned in 10% aqueous NaH2PO4/ethyl acetate mixture. The organic layer is additionally washed with saturated aqueous NaHCO3, dried with anhydrous sodium sulfate and evaporated in vacuum. The obtained compound is purified by chromatography on silicagel (chloroform/isopropanol) to afford 0.46 g of [3-(4-methoxybenzyl)-6-phenyl-3H-imidazo[4,5-b]pyridin-7-yl]methanol x214.

Workup

  1. customThe content of the reactor is evacuated several times
  2. customsubsequently flushed with argon
  3. customThe reactor is equipped with a reflux condenser
  4. customThe whole apparatus is evacuated twice
  5. customsubsequently flushed with argon
  6. customthe obtained solution is partitioned in 10% aqueous NaH2PO4/ethyl acetate mixture
  7. washThe organic layer is additionally washed with saturated aqueous NaHCO3
  8. dry with materialdried with anhydrous sodium sulfate
  9. customevaporated in vacuum
  10. customThe obtained compound is purified by chromatography on silicagel (chloroform/isopropanol)

Sources & evidence

ORD record
ord-27895128af374ca79e7057a1bf590283
Source dataset
uspto-grants-2012_05
Patent number
US08178533B2

Reaction notes

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