Ethyl Acetate → 2-(1-(5-Chloro-2-(pyridin-2-yl)quinolin-3-yl)ethyl)isoindoline-1,3-dione

HRID 1397713Notes

Reaction equation

HRID 1397713 reaction equation
Cl[C:2]1[C:11]([CH: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](=[CH:5][CH:6]=[CH:7][C:8]=2[Cl:25])[N:3]=1.C([Sn](CCCC)(CCCC)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=1)CCC.CCOC(C)=O>C1(C)C=CC=CC=1.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:8]1[CH:7]=[CH:6][CH:5]=[C:4]2[C:9]=1[CH:10]=[C:11]([CH: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])[C:2]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=1)=[N:3]2

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 6077842-(Tributylstannyl)pyridineHCID 577078732-(1-(2,5-Dichloroquinolin-3-yl)ethyl)isoindoline-1,3-dione

Product 1

HCID 577078282-(1-(5-Chloro-2-(pyridin-2-yl)quinolin-3-yl)ethyl)isoindoline-1,3-dione

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

Transferred 2-(1-(2,5-dichloroquinolin-3-yl)ethyl)isoindoline-1,3-dione (197 mg, 531 μmol) from 100 mL flask to 10 mL flask by dissolving/slurrying in toluene and concentrating. Added Pd(Ph3P)4 (61 mg, 53 μmol) and 2-tri-n-butylstannylpyridine (955 μl, 2653 μmmol). Bubbled argon through mixture for 30 sec. Equipped with condenser and nitrogen inlet. Heated at 110° C. for ˜16 h. The reaction mixture was concentrated and chromatographed on 12 g silica gel column with 0-60% EtOAc. The desired fractions were combined and concentrated to yield an oil. NMR indicates residual EtOAc. LC. 1H NMR (400 MHz, DICHLOROMETHANE-d2) δ ppm 1.98 (d, J=7.04 Hz, 3 H) 6.38 (q, J=7.04 Hz, 1 H) 7.24-7.37 (m, 1 H) 7.62-7.76 (m, 8 H) 8.01 (dd, J=8.61, 1.96 Hz, 1 H) 8.56-8.66 (m, 1 H) 9.02 (s, 1 H). −MS (+esi, M+H+=414.1)

Workup

  1. concentrationconcentrating
  2. customEquipped with condenser and nitrogen inlet
  3. concentrationThe reaction mixture was concentrated
  4. customchromatographed on 12 g silica gel column with 0-60% EtOAc
  5. concentrationconcentrated
  6. customto yield an oil

Sources & evidence

ORD record
ord-819d3609fffa4fcfbc6df6ca087d6519
Source dataset
uspto-grants-2014_12
Patent number
US08901135B2

Reaction notes

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