Sodium Carbonate → HCID 178461893, compound

HRID 709945Notes

Reaction equation

HRID 709945 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.[CH3:31][N:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1.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[N:35]2[CH2:36][CH2:37][N:32]([CH3:31])[CH2:33][CH2:34]2)[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 531671-MethylpiperazineHCID 11371790Bis(adamantan-1-yl)(butyl)phosphaneHCID 178461883HCID 178461883, compound

Product 1

HCID 178461893HCID 178461893, 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) (200 mg, 0.48 mmol) and 1-methylpiperazine (0.267 mL, 2.4 mmol) were dissolved in anhydrous NMP (8 mL) and the resulting solution was degassed and back-filled with argon (two cycles). To this mixture, Na2CO3 (102 mg, 0.96 mmol), Pd(OAc)2 (11 mg, 0.048 mmol) and di-(1-adamantyl)-n-butylphosphine (52 mg, 0.144 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 16 h. The reaction mixture was allowed to cool to RT and then partitioned between water and ethyl acetate. The organic layers were 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 with 0.1% TEA) to afford the product, (S)-3-(1-((9H-purin-6-yl)amino)ethyl)-8-(4-methylpiperazin-1-yl)-2-phenylisoquinolin-1(2H)-one (5) as a yellowish solid. ESI-MS m/z: 481.2 [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 layers were 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 with 0.1% TEA)

Sources & evidence

ORD record
ord-da8c92849ca146088c14b2e4ac8b2ef7
Source dataset
uspto-grants-2015_11
Patent number
US09181221B2

Reaction notes

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