Sodium Carbonate → HCID 178435781, compound

HRID 1910883Notes

Reaction equation

HRID 1910883 reaction equation
[N:1]1[C:9]([NH:10][C@H:11]([C:13]2[N:14]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:15](=[O:24])[C:16]3[C:21]([CH:22]=2)=[CH:20][CH:19]=[CH:18][C:17]=3Cl)[CH3:12])=[C:8]2[C:4]([NH:5][CH:6]=[N:7]2)=[N:3][CH:2]=1.[CH2:31]([Sn](CCCC)(CCCC)C=C)[CH2:32]CC.C([O-])([O-])=O.[Na+].[Na+].C12(P(C34CC5CC(CC(C5)C3)C4)CCCC)CC3CC(CC(C3)C1)C2>CN1C(=O)CCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[N:1]1[C:9]([NH:10][C@H:11]([C:13]2[N:14]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:15](=[O:24])[C:16]3[C:21]([CH:22]=2)=[CH:20][CH:19]=[CH:18][C:17]=3[CH:31]=[CH2:32])[CH3:12])=[C:8]2[C:4]([NH:5][CH:6]=[N:7]2)=[N:3][CH:2]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 81998TributylvinyltinHCID 11371790Bis(adamantan-1-yl)(butyl)phosphaneHCID 178461883HCID 178461883, compound

Product 1

HCID 178435781HCID 178435781, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
160 °C

Procedure

(S)-3-(1-((9H-purin-6-yl)amino)ethyl)-8-chloro-2-phenylisoquinolin-1(2H)-one (3) (417 mg, 1.0 mmol) and tributyl(vinyl)tin (0.58 mL, 2.0 mmol) were dissolved in anhydrous NMP (10 mL) and the resulting solution was degassed and back-filled with argon (two cycles). To this mixture, Na2CO3 (212 mg, 2.0 mmol), Pd(OAc)2 (45 mg, 0.2 mmol) and di-(1-adamantyl)-n-butylphosphine (215 mg, 0.6 mmol) were added sequentially. The resulting mixture was degassed and back-filled with argon (two cycles) and then stirred at 160° C. under argon for 1 h. The reaction mixture was allowed to cool to RT and then partitioned between water and ethyl acetate. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by ISCO (silica gel cartridge, 0-10% MeOH-DCM) to afford the product, (S)-3-(1-((9H-purin-6-yl)amino)ethyl)-2-phenyl-8-vinylisoquinolin-1(2H)-one (8) as an off-while solid. ESI-MS m/z: 409.2 [M+H]+.

Workup

  1. customthe resulting solution was degassed
  2. additionback-filled with argon (two cycles)
  3. customThe resulting mixture was degassed
  4. additionback-filled with argon (two cycles)
  5. temperatureto cool to RT
  6. custompartitioned between water and ethyl acetate
  7. customThe organic layer was separated
  8. extractionthe aqueous layer was extracted with ethyl acetate
  9. washThe combined organic layers were washed with brine
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationThe filtrate was concentrated in vacuo
  13. customthe residue was purified by ISCO (silica gel cartridge, 0-10% MeOH-DCM)

Sources & evidence

ORD record
ord-064cbf2256f44c93ad28f84c20b77295
Source dataset
uspto-grants-2013_12
Patent number
US08604032B2

Reaction notes

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