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

HRID 2044909Notes

Reaction equation

HRID 2044909 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 mmol), 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-fc04a52094f84b5289b9a9e299e09e2b
Source dataset
uspto-grants-2013_11
Patent number
US08586739B2

Reaction notes

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