Sodium Carbonate → HCID 178461879, compound

HRID 1910882Notes

Reaction equation

HRID 1910882 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.[NH:31]1[CH:35]=[C:34](B(O)O)[CH:33]=[N:32]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[C:35]2[CH:34]=[CH:33][NH:32][N:31]=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 11371790Bis(adamantan-1-yl)(butyl)phosphaneHCID 177502781H-Pyrazole-4-boronic acidHCID 178461883HCID 178461883, compound

Product 1

HCID 178461879HCID 178461879, 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 1H-pyrazole-4-boronic acid (108 mg, 0.96 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 (152 mg, 1.44 mmol), Pd(OAc)2 (22 mg, 0.096 mmol) and di-(1-adamantyl)-n-butylphosphine (104 mg, 0.288 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 3 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 triturated with Et2O to afford the product, (S)-3-(1-((9H-purin-6-yl)amino)ethyl)-2-phenyl-8-(1H-pyrazol-3-yl)isoquinolin-1(2H)-one (6) as a yellowish solid. ESI-MS m/z: 449.2 [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 triturated with Et2O

Sources & evidence

ORD record
ord-93887e1c280a4fc69801bc36f139d7d2
Source dataset
uspto-grants-2013_12
Patent number
US08604032B2

Reaction notes

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