Sodium Carbonate → 2'-(1-tert-Butoxycarbonylamino-ethyl)-5'-(3-fluoro-pyridin-4-ylcarbamoyl)-biphenyl-3-carboxylic acid

HRID 1403670Notes

Reaction equation

HRID 1403670 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].[C:28]([C:31]1[CH:32]=[C:33](B(O)O)[CH:34]=[CH:35][CH:36]=1)([OH:30])=[O:29].C([O-])([O-])=O.[Na+].[Na+]>COCCOC.CCO.O.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]([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:35]1[CH:34]=[CH:33][CH:32]=[C:31]([C:28]([OH:30])=[O:29])[CH:36]=1)[CH3:9])=[O:27])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 27339573-Carboxyphenylboronic acidHCID 67407943{1-[2-Bromo-4-(3-fluoro-pyridin-4-ylcarbamoyl)-phenyl]-ethyl}-carbamic acid tert-butyl ester

Product 1

HCID 674097672'-(1-tert-Butoxycarbonylamino-ethyl)-5'-(3-fluoro-pyridin-4-ylcarbamoyl)-biphenyl-3-carboxylic acid

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 311Citric AcidSolventHCID 962WaterSolventHCID 86587095Dimethoxyethane ethanol waterSolvent

Conditions

Temperature
130 °C

Procedure

To a solution of {1-[2-bromo-4-(3-fluoro-pyridin-4-ylcarbamoyl)-phenyl]-ethyl}-carbamicacid tert-butyl ester (2841 μmol) and 3-carboxyphenylboronic acid (1.5 eq.) in a mixture of DME/EtOH/water: 1/1/1 (10 ml) was added Na2CO3 (4 eq) and Pd tetrakis (0.05 eq). The reaction mixture was heated in the microwave at 130° C. for 1.5 hours. The reaction mixture was diluted with water and citric acid (to acidic pH) and extracted with EtOAc. The combined organic layers were dried over MgSO4 and the solvent was removed under reduced pressure. The compound was purified by column chromatography (silicagel, DCM/MeOH gradient).

Workup

  1. extractionextracted with EtOAc
  2. dry with materialThe combined organic layers were dried over MgSO4
  3. customthe solvent was removed under reduced pressure
  4. customThe compound was purified by column chromatography (silicagel, DCM/MeOH gradient)

Sources & evidence

ORD record
ord-fda90fd4ed6545158ee75d226cf37f77
Source dataset
uspto-grants-2014_12
Patent number
US08912209B2

Reaction notes

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