Hydrochloric Acid → 2-((S)-1-(8-chloro-2-(2-ethyl-5-fluoropyridin-3-yl)quinolin-3-yl)ethyl)isoindoline-1,3-dione

HRID 2044910Notes

Reaction equation

HRID 2044910 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]1[C:13](Cl)=[N:14][CH:15]=[C:16]([F:18])[CH:17]=1)[C:8]([C@@H:20]([N:22]1[C:30](=[O:31])[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[C:23]1=[O:32])[CH3:21])=[CH:7]2.O1CCO[CH2:35][CH2:34]1.C([Al](CC)CC)C.Cl>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]1[C:13]([CH2:34][CH3:35])=[N:14][CH:15]=[C:16]([F:18])[CH:17]=1)[C:8]([C@@H:20]([N:22]1[C:23](=[O:32])[C:24]3[C:29](=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:30]1=[O:31])[CH3:21])=[CH:7]2

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 16682930TriethylaluminumHCID 866306342-((S)-1-(8-chloro-2-(2-chloro-5-fluoropyridin-3-yl)quinolin-3-yl)-ethyl)isoindoline-1,3-dione

Product 1

HCID 689414082-((S)-1-(8-chloro-2-(2-ethyl-5-fluoropyridin-3-yl)quinolin-3-yl)ethyl)isoindoline-1,3-dione

Reagents, catalysts & solvents 1

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalyst

Procedure

A mixture of 2-((S)-1-(8-chloro-2-(2-chloro-5-fluoropyridin-3-yl)quinolin-3-yl)-ethyl)isoindoline-1,3-dione (192.7 mg, 413 μmol), dioxan (15 mL, 175989 μmol)-, triethylaluminum (236 mg, 2066 μmol) and tetrakis(triphenylphosphine)-palladium (96 mg, 83 μmol) was refluxed for 4 hs under N2, cooled to room temperature. The reaction mixture was acidified with HCl (2N) and the solvent was evaporated. The residue was diluted with water, basified with NaOH (20%), and the mixture was extracted with EtOAc. The combined extracts were washed with water, brine, dried and concentrated. Purification of the residue by flash chromatography over silica gel, gradient elution, 0-100% EtOAc in hexane, gave 2-((S)-1-(8-chloro-2-(2-ethyl-5-fluoropyridin-3-yl)quinolin-3-yl)ethyl)isoindol-ine-1,3-dione, Mass Spectrum (ESI) m/e=460.1 (M+1). And 2-((S)-1-(8-chloro-2-(5-fluoropyridin-3-yl)quinolin-3-yl)ethyl)isoindoline-1,3-dione, Mass Spectrum (ESI) m/e=432.1(M+1).

Workup

  1. temperaturewas refluxed for 4 hs under N2
  2. customthe solvent was evaporated
  3. additionThe residue was diluted with water
  4. extractionthe mixture was extracted with EtOAc
  5. washThe combined extracts were washed with water, brine
  6. customdried
  7. concentrationconcentrated
  8. customPurification of the residue by flash chromatography
  9. washover silica gel, gradient elution, 0-100% EtOAc in hexane

Sources & evidence

ORD record
ord-5848539a27c747789a6df7d85d70ce69
Source dataset
uspto-grants-2013_11
Patent number
US08586739B2

Reaction notes

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