Sodium Carbonate → 4-Phenoxyphenylboronic acid

HRID 1790020Notes

Reaction equation

HRID 1790020 reaction equation
Br[C:2]1[C:10]2[C:5](=[CH:6][N:7]=[N:8][C:9]=2[NH2:11])[N:4]([CH:12]2[CH2:16][CH2:15][CH2:14][CH2:13]2)[CH:3]=1.[O:17]([C:24]1[CH:29]=[CH:28][C:27]([B:30]([OH:32])[OH:31])=[CH:26][CH:25]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.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>[CH:12]1([N:4]2[C:5]3=[CH:6][N:7]=[N:8][C:9]([NH2:11])=[C:10]3[C:2]([C:27]3[CH:28]=[CH:29][C:24]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:25][CH:26]=3)=[CH:3]2)[CH2:16][CH2:15][CH2:14][CH2:13]1.[O:17]([C:24]1[CH:29]=[CH:28][C:27]([B:30]([OH:32])[OH:31])=[CH:26][CH:25]=1)[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 27343774-Phenoxyphenylboronic acidHCID 22037815HCID 22037815, compound

Product 2

HCID 27343774-Phenoxyphenylboronic acidHCID 22037810HCID 22037810, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 3-bromo-1-cyclopentyl-1H-pyrrolo [2,3-d]pyridazin-4-amine (0.057 g, 0.178 mmol), 4-phenoxyphenyl boronic acid (0.057 g, 0.266 mmol), sodium carbonate (0.062 g, 0.588 mmol) and tetrakis(triphenylphosphine)palladium(0) (12 mg, 0.011 mmol) in ethylene glycol dimethyl ether (3 mL) and water (1.5 mL) was heated at 85° C. under an atmosphere of nitrogen for 2.5 hours. The mixture was cooled to ambient temperature and the solvent evaporated under reduced pressure. The residue was purified by preparative reverse phase HPLC to give the title compound contaminated with 4-phenoxyphenyl boronic acid. The residue was partitioned between dichloromethane and 5 N aqueous sodium hydroxide. The organic layer was dried over magnesium sulfate, filtered and the filtrate evaporated to give the title compound (14 mg, 21%); 1H NMR (DMSO-d6, 400 MHz) δ 8.98 (s, 1H), 7.68 (s, 1H),, 7.50 (d, 2H), 7.40 (t, 2H), 7.17 (t, 1H), 7.09 (m, 4H), 5.76 (bs, 2H), 5.01 (m, 1H), 2.19 (m, 2H), 1.91 (m, 2H), 1.71 (m, 2H); 5%–100% acetonitrile-0.05 M ammonium acetate over 25 min, 1 mL/min) tr20.60 min.; LC/MS: MH+ 371.2.

Workup

  1. temperatureThe mixture was cooled to ambient temperature
  2. customthe solvent evaporated under reduced pressure
  3. customThe residue was purified by preparative reverse phase HPLC

Sources & evidence

ORD record
ord-4ee0e95287a3428ba9b400d4a0569d2f
Source dataset
uspto-grants-2006_07
Patent number
US07071199B1

Reaction notes

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