Dichloromethane → 1-(4-Methoxy-phenyl)-3-methyl-6-[4-(2-oxo-piperidin-1-yl)-phenyl]-1,4,5,6-tetrahydro-pyrazolo[3,4-c]pyridin-7-one

HRID 1064065Notes

Reaction equation

HRID 1064065 reaction equation
C(O[C:4]([C:6]1[C:14]2[CH2:13][CH2:12][N:11]([C:15]3[CH:20]=[CH:19][C:18]([N:21]4[CH2:26][CH2:25][CH2:24][CH2:23][C:22]4=[O:27])=[CH:17][CH:16]=3)[C:10](=[O:28])[C:9]=2[N:8]([C:29]2[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=2)[N:7]=1)=O)C.[Li+].[BH4-].C(Cl)Cl.P(Br)(Br)Br>C1COCC1.CC(O)=O.[Zn]>[CH3:36][O:35][C:32]1[CH:31]=[CH:30][C:29]([N:8]2[C:9]3[C:10](=[O:28])[N:11]([C:15]4[CH:20]=[CH:19][C:18]([N:21]5[CH2:26][CH2:25][CH2:24][CH2:23][C:22]5=[O:27])=[CH:17][CH:16]=4)[CH2:12][CH2:13][C:14]=3[C:6]([CH3:4])=[N:7]2)=[CH:34][CH:33]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 24614Phosphorus tribromideHCID 4148881Lithium borohydrideHCID 22240488ethyl 1-(4-methoxyphenyl)-7-oxo-6-(4-(2-oxo-1-piperidinyl)phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylate

Product 1

HCID 222404521-(4-Methoxy-phenyl)-3-methyl-6-[4-(2-oxo-piperidin-1-yl)-phenyl]-1,4,5,6-tetrahydro-pyrazolo[3,4-c]pyridin-7-oneYield 58%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To 1-(4-methoxy-phenyl)-7-oxo-6-[4-(2-oxo-piperidin-1-yl)-phenyl]-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid ethyl ester (0.59 g, 1.2 mmol) in THF (25 mL) was added 2M LiBH4 in THF(0.96 mL, 1.9 mmol) and the reaction was heated to reflux for 2.5 h. To the crude alcohol were added CH2Cl2 (25 mL) and PBr3 (0.14 mL) and the reaction was stirred 24 h. Extraction with CHCl3, washing with water, and drying (Na2SO4) afforded a crude bromo-compound. The bromo-compound was heated in AcOH (15 mL) and activated Zn (0.39 g, 6 mmol) at 120° C. for 24 h. Purification by HPLC and freeze-drying afforded 30 mg (58%) of a white solid; High Resolution Mass Spec (M+H)+ for C25H27N4O3 431.2092.

Workup

  1. temperaturethe reaction was heated
  2. temperatureto reflux for 2.5 h
  3. extractionExtraction with CHCl3
  4. washwashing with water
  5. dry with materialdrying (Na2SO4)
  6. customafforded a crude bromo-compound
  7. customPurification by HPLC
  8. customfreeze-drying

Sources & evidence

ORD record
ord-4aba6a4f056f40a28989c892d80cf06f
Source dataset
uspto-grants-2005_11
Patent number
US06967208B2

Reaction notes

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