3-Aminophenylboronic acid → {1-[3'-Amino-5-(3-fluoro-pyridin-4-ylcarbamoyl)-biphenyl-2-yl]-ethyl}-carbamic acid tert-butyl ester

HRID 2409370Notes

Reaction equation

HRID 2409370 reaction equation
[C:1]([O:5][C:6](=[O:27])[NH:7][CH:8]([C:10]1[CH:15]=[CH:14][C:13]([C:16](=[O:25])[NH:17][C:18]2[CH:23]=[CH:22][N:21]=[CH:20][C:19]=2[F:24])=[CH:12][C:11]=1Br)[CH3:9])([CH3:4])([CH3:3])[CH3:2].[NH2:28][C:29]1[CH:30]=[C:31](B(O)O)[CH:32]=[CH:33][CH:34]=1>COCCOC.C(O)C.O.C(O)(=O)CC(CC(O)=O)(C(O)=O)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>[C:1]([O:5][C:6](=[O:27])[NH:7][CH:8]([C:10]1[CH:15]=[CH:14][C:13]([C:16](=[O:25])[NH:17][C:18]2[CH:23]=[CH:22][N:21]=[CH:20][C:19]=2[F:24])=[CH:12][C:11]=1[C:33]1[CH:32]=[CH:31][CH:30]=[C:29]([NH2:28])[CH:34]=1)[CH3:9])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 2

HCID 922693-Aminophenylboronic acidHCID 67407943{1-[2-Bromo-4-(3-fluoro-pyridin-4-ylcarbamoyl)-phenyl]-ethyl}-carbamic acid tert-butyl ester

Product 1

HCID 67422654{1-[3'-Amino-5-(3-fluoro-pyridin-4-ylcarbamoyl)-biphenyl-2-yl]-ethyl}-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 311Citric AcidSolventHCID 962WaterSolventHCID 20074477Dimethoxyethane ethanolSolvent

Conditions

Temperature
130 °C

Procedure

To a solution of {1-[2-bromo-4-(3-fluoro-pyridine-4-ylcarbamoyl)-phenyl]-ethyl}-carbamic acid tert-butyl ester (1094 μmol) and 3-aminophenylboronic acid (2 eq) in a mixture of DME/ethanol/1N Na2CO3: 1/1/1 (10 ml) was added Pd tetrakis (0.05 eq). The reaction mixture was heated in the microwave at 130° C. for 1.5 hours. The reaction mixture was cooled to RT and diluted with water and citric acid and extracted with EtOAc. The combined organic layers were washed with water and brine. The organic layer was dried over MgSO4 and the solvent was removed under reduced pressure. The compound was purified by column chromatography (silicagel, DCM/MeOH gradient).

Workup

  1. temperatureThe reaction mixture was cooled to RT
  2. extractionextracted with EtOAc
  3. washThe combined organic layers were washed with water and brine
  4. dry with materialThe organic layer was dried over MgSO4
  5. customthe solvent was removed under reduced pressure
  6. customThe compound was purified by column chromatography (silicagel, DCM/MeOH gradient)

Sources & evidence

ORD record
ord-c3eada46c6444010a26a5673963ef94d
Source dataset
uspto-grants-2014_08
Patent number
US08815873B2

Reaction notes

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