Diethyl Ether → 1-[2-methyl-7-(2,4,6-trimethyl-phenyl)-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridine-3-yl]ethanone

HRID 2113799Notes

Reaction equation

HRID 2113799 reaction equation
Br[C:2]1[N:3]([CH3:20])[N:4]=[C:5]2[C:10]=1[CH2:9][CH2:8][CH2:7][N:6]2[C:11]1[C:16]([CH3:17])=[CH:15][C:14]([CH3:18])=[CH:13][C:12]=1[CH3:19].C([Li])CCC.CCCCCC.[CH3:32][CH2:33][O:34]CC.C(Cl)(=O)C.[Cl-].[NH4+]>C1COCC1.[Cl-].[Zn+2].[Cl-].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:20][N:3]1[C:2]([C:33](=[O:34])[CH3:32])=[C:10]2[C:5]([N:6]([C:11]3[C:16]([CH3:17])=[CH:15][C:14]([CH3:18])=[CH:13][C:12]=3[CH3:19])[CH2:7][CH2:8][CH2:9]2)=[N:4]1

Participants

10

Reactant 6

HCID 3283Diethyl EtherHCID 6367Acetyl chlorideHCID 8058HexaneHCID 25517Ammonium ChlorideHCID 112328983-bromo-2-methyl-7-(2,4,6-trimethylphenyl)-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridineHCID 178418339Butyllithium

Product 1

HCID 598115151-[2-methyl-7-(2,4,6-trimethyl-phenyl)-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridine-3-yl]ethanoneYield 6.4%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 3-bromo-2-methyl-7-(2,4,6-trimethyl-phenyl)-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridine (1-3; 0.040 g, 1.2 mmol) in 6 mL of dry THF was cooled to −78° C. in a dry ice-acetone bath under an argon atmosphere and treated with n-butyllithium in hexane (0.83 mL, 1.32 mmol). After 10 m a solution of 1 M zinc chloride in ether (3.59 mL, 3.59 mmol) was added. The cooling bath was removed and the reaction stirred at room temperature. After 10 m acetyl chloride (0.113 g, 1.44 mmol) and tetrakis(triphenylphosphine)palladium(0) (28 mg, 0.024 mmol) were added and the brown solution was stirred for 2 hrs. The mixture was poured into 25 mL of saturated ammonium chloride solution, extracted twice with 25 mL portions of ethyl acetate. The combined organic extracts were washed with brine, dried over magnesium sulfate, and evaporated to dryness. The residue was purified on flash chromatography on silica gel eluting with ethyl acetate/hexane (15:85) giving 23 mg (6% yield) of 1-[2-methyl-7-(2,4,6-trimethyl-phenyl)-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridine-3-yl]ethanone as a colorless oil: ms (M+H)+=298.

Workup

  1. customThe cooling bath was removed
  2. stirringthe brown solution was stirred for 2 hrs
  3. extractionextracted twice with 25 mL portions of ethyl acetate
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over magnesium sulfate
  6. customevaporated to dryness
  7. customThe residue was purified on flash chromatography on silica gel eluting with ethyl acetate/hexane (15:85)

Sources & evidence

ORD record
ord-e15b6764b1b84d24b0df1f45351bd7f5
Source dataset
uspto-grants-2008_10
Patent number
US07432283B2

Reaction notes

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