Sodium Carbonate → 3-(1H-indol-5-yl)-5-(3-methoxy-4-(2-(piperazin-1-yl)ethoxy)phenyl)-1H-pyrrolo[2,3-b]pyridine

HRID 712539Notes

Reaction equation

HRID 712539 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[CH:12]=[C:13]4[C:17](=[CH:18][CH:19]=3)[NH:16][CH:15]=[CH:14]4)=[CH:9][N:8](S(C3C=CC(C)=CC=3)(=O)=O)[C:5]2=[N:6][CH:7]=1.[CH3:30][O:31][C:32]1[CH:46]=[C:45](B2OC(C)(C)C(C)(C)O2)[CH:44]=[CH:43][C:33]=1[O:34][CH2:35][CH2:36][N:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1.C([O-])([O-])=O.[Na+].[Na+].[OH-].[Na+]>CC#N.CO.CC(C)=O.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:16]1[C:17]2[C:13](=[CH:12][C:11]([C:10]3[C:4]4[C:5](=[N:6][CH:7]=[C:2]([C:45]5[CH:44]=[CH:43][C:33]([O:34][CH2:35][CH2:36][N:37]6[CH2:38][CH2:39][NH:40][CH2:41][CH2:42]6)=[C:32]([O:31][CH3:30])[CH:46]=5)[CH:3]=4)[NH:8][CH:9]=3)=[CH:19][CH:18]=2)[CH:14]=[CH:15]1

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 14798Sodium HydroxideHCID 667791765-bromo-3-(1H-indol-5-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine2×HCID 667799091-(2-(2-Methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)ethyl)piperazine

Product 1

HCID 462345053-(1H-indol-5-yl)-5-(3-methoxy-4-(2-(piperazin-1-yl)ethoxy)phenyl)-1H-pyrrolo[2,3-b]pyridine

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 180AcetoneSolventHCID 887MethanolSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 5-bromo-3-(1H-indol-5-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine (Intermediate B) (92 mg, 0.20 mmol) in CH3CN (2 mL) in a Personal Chemistry microwave reaction vial was added 1-(2-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)ethyl)piperazine (Intermediate AM) (72 mg, 0.20 mmol), bis(triphenylphosphine)-palladium(II) dichloride (20 mg, 0.028 mmol), and 1 M Na2CO3 (2 mL). The resulting mixture was de-gassed with Ar for 10 min, after which it was heated at 150° C. for 25 min in a Personal Chemistry Optimizer. The organic layer was separated, filtered, and concentrated in vacuo to give Intermediate AN. 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 50° C. for 2 h, 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 that was subjected to preparatory HPLC to yield the title compound. HPLC retention time: 1.29 minutes; MS ESI (m/z) 468.6 (M+1)+, calc. 467.

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. customto give Intermediate AN
  6. customafter which it was partitioned between EtOAc and 1 M NaOH
  7. customThe organic layer was separated
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. customto give a residue that

Sources & evidence

ORD record
ord-91420b4279224497af83381a2ffe66cb
Source dataset
uspto-grants-2015_11
Patent number
US09181247B2

Reaction notes

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