Carbonic Acid → 2-(((S)-1-(8-chloro-2-(2,3-difluorophenyl)quinolin-3-yl)ethyl)carbamoyl)benzoic acid

HRID 2044966Notes

Reaction equation

HRID 2044966 reaction equation
Cl[C:2]1[C:11]([C@@H:12]([N:14]2[C:22](=[O:23])[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15]2=[O:24])[CH3:13])=[CH:10][C:9]2[C:4](=[C:5]([Cl:25])[CH:6]=[CH:7][CH:8]=2)[N:3]=1.[F:26][C:27]1[C:32]([F:33])=[CH:31][CH:30]=[CH:29][C:28]=1B(O)O.C(O)(O)=[O:38].C(#N)C.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>[Cl:25][C:5]1[CH:6]=[CH:7][CH:8]=[C:9]2[C:4]=1[N:3]=[C:2]([C:31]1[CH:30]=[CH:29][CH:28]=[C:27]([F:26])[C:32]=1[F:33])[C:11]([C@@H:12]([NH:14][C:15]([C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][C:21]=1[C:22]([OH:23])=[O:38])=[O:24])[CH3:13])=[CH:10]2

Participants

6

Reactant 4

HCID 767Carbonic AcidHCID 2734333(2,3-Difluorophenyl)boronic acidHCID 18373917Acetonitrile--water (1/1)HCID 57707774(S)-2-(1-(2,8-dichloroquinolin-3-yl)ethyl)isoindoline-1,3-dione

Product 1

HCID 577078862-(((S)-1-(8-chloro-2-(2,3-difluorophenyl)quinolin-3-yl)ethyl)carbamoyl)benzoic acid

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
85 °C

Procedure

A mixture of (S)-2-(1-(2,8-dichloroquinolin-3-yl)ethyl)isoindoline-1,3-dione (0.2000 g, 0.5388 mmol), 2,3-difluorobenzeneboronic acid (0.09358 g, 0.5926 mmol), tetrakis(triphenylphosphine)palladium (0.03113 g, 0.02694 mmol), and sodium carbonate anhydrous (0.2855 g, 2.694 mmol) in acetonitrile-water (3:1) (5.200 mL, 0.5387 mmol) was stirred at 85° C. After 19 h, the mixture was cooled to room temperature and partitioned between CH2Cl2 (30 mL) and 2 N HCl (30 mL). The organic layer was washed with brine (50 mL×2), dried over Na2SO4, filtered, and concentrated under reduced pressure to give 2-(((S)-1-(8-chloro-2-(2,3-difluorophenyl)quinolin-3-yl)ethyl)carbamoyl)benzoic acid as a yellow foam type solid: LC-MS (ESI) m/z 467.0 [M+H]+.

Workup

  1. temperaturethe mixture was cooled to room temperature
  2. custompartitioned between CH2Cl2 (30 mL) and 2 N HCl (30 mL)
  3. washThe organic layer was washed with brine (50 mL×2)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-88cdabe44ce742b488d7897a9f10dd07
Source dataset
uspto-grants-2013_11
Patent number
US08586739B2

Reaction notes

Loading…