Potassium Carbonate → HCID 66831367, compound

HRID 405988Notes

Reaction equation

HRID 405988 reaction equation
Br[C:2]1[C:7](=[O:8])[N:6]2[CH:9]=[CH:10][CH:11]=[CH:12][C:5]2=[N:4][C:3]=1[CH:13]([N:15]1[C:23](=[O:24])[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[C:16]1=[O:25])[CH3:14].[CH3:26][S:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1B(O)O.C(=O)([O-])[O-].[K+].[K+]>COCCOC.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>[CH3:26][S:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[C:2]1[C:7](=[O:8])[N:6]2[CH:9]=[CH:10][CH:11]=[CH:12][C:5]2=[N:4][C:3]=1[CH:13]([N:15]1[C:23](=[O:24])[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[C:16]1=[O:25])[CH3:14]

Participants

6

Reactant 3

HCID 11430Potassium Carbonate2×HCID 27735432-(Methylthio)benzeneboronic acid2×HCID 58796945HCID 58796945, compound

Product 1

HCID 66831367HCID 66831367, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 2-(1-(3-bromo-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)ethyl)isoindoline-1,3-dione (0.9836 g, 2.470 mmol), 2-(methylthio)phenylboronic acid (0.623 g, 3.71 mmol), tetrakis(triphenylphosphine)palladium(0) (0.143 g, 0.124 mmol), and potassium carbonate (1.024 g, 7.41 mmol) in DME (12.35 mL) was stirred at 85° C. After 25.5 h, to the mixture were added 2-(methylthio)phenylboronic acid (0.623 g, 3.71 mmol), tetrakis(triphenylphosphine)palladium(0) (0.143 g, 0.124 mmol), and potassium carbonate (1.024 g, 7.41 mmol) and the mixture was stirred at 85° C. After 4 days 21 h, the mixture was cooled to rt. The insoluble solid was filtered off and the solid was washed with DCM (50 mL). The filtrate was cond under reduced pressure. The residue was dissolved in DCM (50 mL), washed with brine (50 mL×2), dried over Na2SO4, filtered, and cond under reduced pressure. The residue was purified by silica gel column chromatography on a 40 g Redi-Sep™ column using 0 to 50% gradient of EtOAc in hexane over 14 min and then 50% isocratic of EtOAc for 20 min as eluent to give 2-(1-(3-(2-(methylthio)phenyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)ethyl)isoindoline-1,3-dione as a yellow syrup: 1H NMR (400 MHz, DMSO-d6) δ ppm 8.96 (1 H, ddd, J=7.2, 1.6, 0.8 Hz), 7.98-8.05 (1 H, m), 7.77-7.84 (2 H, m), 7.68-7.75 (3 H, m), 7.43 (1 H, td, J=6.9, 1.5 Hz), 7.31 (1 H, dd, J=8.1, 0.9 Hz), 7.18-7.24 (1 H, m), 6.79-6.85 (1 H, m), 6.70-6.76 (1 H, m), 5.36-5.44 (1 H, m), 2.41 (3 H, s), 1.64 (3 H, d, J=7.2 Hz); Mass Spectrum (ESI) m/e=442.1 (M+1).

Workup

  1. stirringthe mixture was stirred at 85° C
  2. waitAfter 4 days 21 h
  3. temperaturethe mixture was cooled to rt
  4. filtrationThe insoluble solid was filtered off
  5. washthe solid was washed with DCM (50 mL)
  6. dissolutionThe residue was dissolved in DCM (50 mL)
  7. washwashed with brine (50 mL×2)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. customThe residue was purified by silica gel column chromatography on a 40 g Redi-Sep™ column
  11. customover 14 min

Sources & evidence

ORD record
ord-848145c0e9d6465ea3e4e936cddd9a28
Source dataset
uspto-grants-2014_06
Patent number
US08754089B2

Reaction notes

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