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

HRID 216833Notes

Reaction equation

HRID 216833 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.[Cl:26][C:27]1[C:32](B(O)O)=[CH:31][C:30]([F:36])=[CH:29][N:28]=1.[F-].[Cs+].COC>C(O)CO.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.[Cu]I>[Cl:25][C:5]1[CH:6]=[CH:7][CH:8]=[C:9]2[C:4]=1[N:3]=[C:2]([C:32]1[C:27]([Cl:26])=[N:28][CH:29]=[C:30]([F:36])[CH:31]=1)[C:11]([C@@H:12]([N:14]1[C:22](=[O:23])[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15]1=[O:24])[CH3:13])=[CH:10]2

Participants

8

Reactant 4

HCID 8254Dimethyl EtherHCID 25953Cesium fluorideHCID 249017742-Chloro-5-fluoropyridine-3-boronic acidHCID 57707774(S)-2-(1-(2,8-dichloroquinolin-3-yl)ethyl)isoindoline-1,3-dione

Product 1

HCID 866306342-((S)-1-(8-chloro-2-(2-chloro-5-fluoropyridin-3-yl)quinolin-3-yl)-ethyl)isoindoline-1,3-dione

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 174Ethylene GlycolSolvent

Procedure

A mixture of (S)-2-(1-(2,8-dichloroquinolin-3-yl)ethyl)isoindoline-1,3-dione (120.0 mg, 323 μmol), 2-chloro-5-fluoropyridin-3-ylboronic acid (57 mg, 323 μmol), tetrakis(triphenylphosphine)palladium (37 mg, 32 μmol), cesium fluoride (147 mg, 970 μmol) and copper(I) iodide (12 mg, 65 μmol) in 1,2-ethanediol, dimethyl ether (3.0 mL, 323 μmol) was subjected to microwave at 100° C. for 1 h, cooled to room temperature. Filtration of the resultant mixture and rinsed with EtOAc, the filtrates were collected 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-chloro-5-fluoropyridin-3-yl)quinolin-3-yl)-ethyl)isoindoline-1,3-dione, Mass Spectrum (ESI) m/e=466.0 (M+1).

Workup

  1. filtrationFiltration of the resultant mixture
  2. washrinsed with EtOAc
  3. customthe filtrates were collected
  4. concentrationconcentrated
  5. customPurification of the residue by flash chromatography
  6. washover silica gel, gradient elution, 0-100% EtOAc in hexane

Sources & evidence

ORD record
ord-37268f7654a44db099f0eb1be010f936
Source dataset
uspto-grants-2012_06
Patent number
US08193199B2

Reaction notes

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