Hydrochloric Acid → 2-((S)-1-(7-fluoro-2-(3-fluorophenyl)quinolin-3-yl)ethyl)isoindoline-1,3-dione

HRID 75365Notes

Reaction equation

HRID 75365 reaction equation
[F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C@@H:19]([NH:21][C:22]([C:24]3[CH:32]=[CH:31][CH:30]=[CH:29][C:25]=3[C:26](O)=[O:27])=[O:23])[CH3:20])[C:8]([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=3)=[N:9]2)=[CH:4][CH:3]=1.Cl>CCO>[F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C@@H:19]([N:21]3[C:22](=[O:23])[C:24]4[C:25](=[CH:29][CH:30]=[CH:31][CH:32]=4)[C:26]3=[O:27])[CH3:20])[C:8]([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=3)=[N:9]2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 867272892-(((S)-1-(7-fluoro-2-(3-fluorophenyl)quinolin-3-yl)ethyl)carbamoyl)benzoic acid

Product 1

HCID 866985052-((S)-1-(7-fluoro-2-(3-fluorophenyl)quinolin-3-yl)ethyl)isoindoline-1,3-dioneYield 49%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of (S)-2-(1-(2-chloro-7-fluoroquinolin-3-yl)ethyl)isoindoline-1,3-dione (150 mg, 423 μmol), 3-fluorophenylboronic acid (65 mg, 465 μmol) and sodium carbonate (90 mg, 846 μmol) in MeCN (8 mL) and water (2 mL) was purged with N2 followed by the addition of Pd(PPh3)4 (24 mg, 21 μmol) and the resulting mixture was stirred at 90° C. overnight. The reaction mixture was diluted with EtOAc washed with water, brine and dried over Na2SO4. Purification using preparatory TLC eluted with 100% EtOAc afforded 2-(((S)-1-(7-fluoro-2-(3-fluorophenyl)quinolin-3-yl)ethyl)carbamoyl)benzoic acid (120 mg, 66%). Mass Spectrum (ESI) m/e=433 (M+1). 2-(((S)-1-(7-Fluoro-2-(3-fluorophenyl)-quinolin-3-yl)ethyl)carbamoyl)benzoic acid was dissolved in EtOH (2 mL) and cond HCl (0.1 mL) was added. The resulting solution was heated to 80° C. for 4 h. Solvent was removed and satd NaHCO3 was added to the reaction mixture and extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4, concentrated and purified via preparatory TLC using 3% MeOH/DCM saturated with NH3 gas to afford a white solid of 2-((S)-1-(7-fluoro-2-(3-fluorophenyl)quinolin-3-yl)ethyl)isoindoline-1,3-dione (85 mg, 49%). Mass Spectrum (ESI) m/e=415 (M+1).

Workup

  1. customSolvent was removed
  2. additionwas added to the reaction mixture
  3. extractionextracted with EtOAc
  4. washThe organic layer was washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. custompurified via preparatory TLC

Sources & evidence

ORD record
ord-7774df003dd443cabd3aeebe428cd147
Source dataset
uspto-grants-2014_09
Patent number
US08835432B2

Reaction notes

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