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

HRID 892329Notes

Reaction equation

HRID 892329 reaction equation
O[CH2:2][C:3]1[C:11]2[CH2:10][CH2:9][N:8]([C:12]3[CH:17]=[CH:16][C:15]([N:18]4[CH:23]=[CH:22][CH:21]=[CH:20][C:19]4=[O:24])=[CH:14][CH:13]=3)[C:7](=[O:25])[C:6]=2[N:5]([C:26]2[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=2)[N:4]=1.C([SiH](CC)CC)C.C(O)(C(F)(F)F)=O.C(O)(=O)C>C(Cl)Cl>[CH3:33][O:32][C:29]1[CH:28]=[CH:27][C:26]([N:5]2[C:6]3[C:7](=[O:25])[N:8]([C:12]4[CH:17]=[CH:16][C:15]([N:18]5[CH:23]=[CH:22][CH:21]=[CH:20][C:19]5=[O:24])=[CH:14][CH:13]=4)[CH2:9][CH2:10][C:11]=3[C:3]([CH3:2])=[N:4]2)=[CH:31][CH:30]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 6422Trifluoroacetic acid3×HCID 12052Triethylsilane3×HCID 10138256HCID 10138256, compound

Product 1

HCID 101372751-(4-Methoxy-phenyl)-3-methyl-6-[4-(2-oxo-2H-pyridin-1-yl)-phenyl]-1,4,5,6-tetrahydro-pyrazolo[3,4-c]pyridin-7-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

To 3-hydroxymethyl-1-(4-methoxy-phenyl)-6-[4-(2-oxo-2H-pyridin-1-yl)-phenyl]-1,4,5,6-tetrahydro-pyrazolo[3,4-c]pyridin-7-one (65 mg, 0.15 mmol) in CH2Cl2 (10 mL) was added triethylsilane (0.1 mL) and TFA (0.05 mL). After 2 h more triethylsilane (0.2 mL) and TFA (0.1 mL) were added and the reaction was stirred for 72 h. The reaction was not proceeding so the solvents were stripped and replaced with acetic acid (10 mL), triethylsilane (0.5 mL), and TFA (0.1 mL). The reaction was heated 24 h at 80° C. Mass spectra indicated only the acetyl product formed. The solvents were removed. The acetyl group was removed by stirring with LiOH (0.1 g) in THF/H2O for 3 h. The reaction was quenched with 1N HCl, extracted with EtOAc, and dried (MgSO4) to recover the alcohol. To the alcohol in CHCl3 was added PBr3 and the reaction was stirred 24 h. The reaction was quenched with ice water, extracted with CHCl3, and dried (Na2SO4). To the crude bromide were added activated Zn (80 mg) and acetic acid (10 mL) and heated to 120° C. for 24 h. The product was purified by silica gel chromatography using 0–3% MeOH in CH2Cl2 and recrystallized from CH3CN/H2O to afford 22 mg (35%); Mass Spec (M+H)+ 427.3.

Workup

  1. customformed
  2. customThe solvents were removed
  3. customThe acetyl group was removed
  4. stirringby stirring with LiOH (0.1 g) in THF/H2O for 3 h
  5. customThe reaction was quenched with 1N HCl
  6. extractionextracted with EtOAc
  7. dry with materialdried (MgSO4)
  8. customto recover the alcohol
  9. additionTo the alcohol in CHCl3 was added PBr3
  10. stirringthe reaction was stirred 24 h
  11. customThe reaction was quenched with ice water
  12. extractionextracted with CHCl3
  13. dry with materialdried (Na2SO4)
  14. additionTo the crude bromide were added activated Zn (80 mg) and acetic acid (10 mL)
  15. temperatureheated to 120° C. for 24 h
  16. customThe product was purified by silica gel chromatography
  17. customrecrystallized from CH3CN/H2O
  18. customto afford 22 mg (35%)

Sources & evidence

ORD record
ord-cecd94c30b934c0a81afb230c4f77879
Source dataset
uspto-grants-2006_02
Patent number
US07005435B2

Reaction notes

Loading…