Sodium Carbonate → 7-(1H-indol-5-yl)-2-(3,4,5-trimethoxyphenyl)-5H-pyrrolo[3,2-b]pyrazine

HRID 712546Notes

Reaction equation

HRID 712546 reaction equation
Br[C:2]1[N:7]=[C:6]2[C:8]([C:21]3[CH:22]=[C:23]4[C:27](=[CH:28][CH:29]=3)[NH:26][CH:25]=[CH:24]4)=[CH:9][N:10](S(C3C=CC(C)=CC=3)(=O)=O)[C:5]2=[N:4][CH:3]=1.[CH3:30][O:31][C:32]1[CH:33]=[C:34](B(O)O)[CH:35]=[C:36]([O:40][CH3:41])[C:37]=1[O:38][CH3:39].C([O-])([O-])=O.[Na+].[Na+]>CC#N.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH:26]1[C:27]2[C:23](=[CH:22][C:21]([C:8]3[C:6]4=[N:7][C:2]([C:34]5[CH:35]=[C:36]([O:40][CH3:41])[C:37]([O:38][CH3:39])=[C:32]([O:31][CH3:30])[CH:33]=5)=[CH:3][N:4]=[C:5]4[NH:10][CH:9]=3)=[CH:29][CH:28]=2)[CH:24]=[CH:25]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27343903,4,5-Trimethoxybenzeneboronic acidHCID 866626782-bromo-7-(1H-indol-5-yl)-5-tosyl-5H-pyrrolo[3,2-b]pyrazine

Product 1

HCID 462345077-(1H-indol-5-yl)-2-(3,4,5-trimethoxyphenyl)-5H-pyrrolo[3,2-b]pyrazine

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 2-bromo-7-(1H-indol-5-yl)-5-tosyl-5H-pyrrolo[3,2-b]pyrazine [Intermediate AV] (65 mg, 0.14 mmol) in CH3CN (1 mL) in a Personal Chemistry microwave reaction vial was added 3,4,5-trimethoxyphenylboronic acid (30 mg, 0.14 mmol), bis(triphenylphosphine)-palladium(II) dichloride (7.0 mg, 0.010 mmol), and 1 M Na2CO3 (1 mL). The resulting mixture was de-gassed with Ar for 10 min, after which it was heated at 150° C. for 10 min in a Personal Chemistry Optimizer. The organic layer was separated, filtered, and concentrated in vacuo. The residue was dissolved in MeOH (3 mL) and acetone (2 mL), and 2 M NaOH (1.5 mL) was added. The resulting mixture was stirred at 65° C. for 30 min, after which it was partitioned between EtOAc and 1 M NaOH. The organic layer was separated, dried over MgSO4, filtered, and stripped to give a residue which was purified by preparatory HPLC to give the title compound as a yellow solid. HPLC retention time: 2.25 minutes; MS ESI (m/z) 401.2 (M+1)+, calc. 400.

Workup

  1. customThe resulting mixture was de-gassed with Ar for 10 min
  2. customThe organic layer was separated
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was dissolved in MeOH (3 mL)
  6. additionacetone (2 mL), and 2 M NaOH (1.5 mL) was added
  7. customafter which it was partitioned between EtOAc and 1 M NaOH
  8. customThe organic layer was separated
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. customto give a residue which
  12. customwas purified by preparatory HPLC

Sources & evidence

ORD record
ord-bfad56897dcf410ea28fe2014d24ef78
Source dataset
uspto-grants-2015_11
Patent number
US09181247B2

Reaction notes

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