Water → HCID 57475530, compound

HRID 2404247Notes

Reaction equation

HRID 2404247 reaction equation
Br[C:2]1[C:14]2[C:13]3[CH:12]=[C:11](OC)[C:10](OC)=[CH:9][C:8]=3[N:7]=[CH:6][C:5]=2[N:4](C)[N:3]=1.[OH-].[K+].CC1(C)C(C)(C)OB(C2C=CC(N3CCN(C(OC(C)(C)C)=O)CC3)=CC=2)O1.O>O1CCOCC1>[CH:2]1[C:14]2[C:13]3[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=3[N:7]=[CH:6][C:5]=2[NH:4][N:3]=1

Participants

6

Reactant 4

HCID 962Water2×HCID 14797Potassium HydroxideHCID 27955144-(4-tert-Butoxycarbonylpiperazinyl)phenylboronic acid, pinacol esterHCID 66633095HCID 66633095, compound

Product 1

HCID 57475530HCID 57475530, compoundYield 59.1%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

1-Bromo-7,8-dimethoxy-3-methyl-3H-pyrazolo[3,4-c]quinoline (30 mg, 93 μmol) is dissolved in dioxane (1.0 ml) under argon. KOH (5.2 mg, 93 μmol), tert-butyl 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine-1-carboxylate (83 mg, 214 μmol), trans-bis(tricyclohexylphosphine)palladium(II) dichloride (10.4 mg, 14 μmol) and water (50 μl) are subsequently added. The reaction suspension is subsequently heated at 110° C. (microwave) for 90 min. The mixture is subsequently poured into water, stirred for 15 min, and the precipitate obtained is filtered off with suction. The filter residue is then treated in formic acid (2.5 ml) at room temperature for 18 h, subsequently diluted with water and extracted twice with ethyl acetate. The combined organic phases are washed with water, dried over Na2SO4, filtered with suction and evaporated to dryness in vacuo. The residue is purified by chromatography (pHPLC, solvent gradient water/1-30% by vol. of acetonitrile, 0.1% by vol. of formic acid), and the product fractions are freeze-dried, giving 7,8-dimethoxy-3-methyl-1-(4-piperazin-1-yl)phenyl)-3H-pyrazolo[3,4-c]quinoline (22 mg, 55 μmol) as a solid. MS: 404.1 (M+H+). TLC (HPTLC): Rf=0.19 (methanol/Hünig's base 99:1, parts by volume).

Workup

  1. customthe precipitate obtained
  2. filtrationis filtered off with suction
  3. additionThe filter residue is then treated in formic acid (2.5 ml) at room temperature for 18 h
  4. additionsubsequently diluted with water
  5. extractionextracted twice with ethyl acetate
  6. washThe combined organic phases are washed with water
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered with suction
  9. customevaporated to dryness in vacuo
  10. customThe residue is purified by chromatography (pHPLC, solvent gradient water/1-30% by vol. of acetonitrile, 0.1% by vol. of formic acid)
  11. customthe product fractions are freeze-dried

Sources & evidence

ORD record
ord-c60e6e54edb44085aec5fce79f1c744a
Source dataset
uspto-grants-2014_08
Patent number
US08802712B2

Reaction notes

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