1-Methylpiperazine → 6-(4-methylpiperazin-1-yl)-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine

HRID 1025620Notes

Reaction equation

HRID 1025620 reaction equation
Br[C:2]1[N:7]=[C:6]2[N:8]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])[CH:9]=[CH:10][C:5]2=[CH:4][CH:3]=1.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.[CH3:34][N:35]1[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1.CC(C)([O-])C.[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CCOC(C)=O.C1(C)C=CC=CC=1>[CH3:34][N:35]1[CH2:40][CH2:39][N:38]([C:2]2[N:7]=[C:6]3[N:8]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])[CH:9]=[CH:10][C:5]3=[CH:4][CH:3]=2)[CH2:37][CH2:36]1

Participants

8

Reactant 4

HCID 531671-MethylpiperazineHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 23676156Sodium t-butoxideHCID 580876901H-Pyrrolo[2,3-b]pyridine, 6-bromo-1-[tris(1-methylethyl)silyl]-

Product 1

HCID 710086036-(4-methylpiperazin-1-yl)-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridineYield 60%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

In a 25 mL round-bottomed flask, 6-bromo-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine (520 mg, 1.47 mmol, Eq: 1.00), palladium (II) acetate (165 mg, 736 μmol, Eq: 0.5) and tri-tert-butylphosphine (149 mg, 182 μl, 736 μmol, Eq: 0.5) were combined with toluene to give a yellow solution. 1-methylpiperazine (442 mg, 491 μl, 4.41 mmol, Eq: 3) and sodium tert-butoxide (424 mg, 4.41 mmol, Eq: 3) were added. The reaction mixture was heated to 80° C. and stirred for 1 h. The reaction mixture was poured into 20 mL EtOAc and extracted with sat NaCl (3×20 mL). The organic layers were dried over MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 12 g, 2% to 5% MeOH in DCM) to give 6-(4-methylpiperazin-1-yl)-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine (326 mg, 60%) as yellow oil that solidified upon standing.

Workup

  1. customto give a yellow solution
  2. extractionextracted with sat NaCl (3×20 mL)
  3. dry with materialThe organic layers were dried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe crude material was purified by flash chromatography (silica gel, 12 g, 2% to 5% MeOH in DCM)

Sources & evidence

ORD record
ord-32c64b5ebd87422380a43de0b8191758
Source dataset
uspto-grants-2014_05
Patent number
US08729078B2

Reaction notes

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