Lithium Chloride → 5-(2-Butoxy-5-[2-pyridyl]-3-pyridinyl)-3-ethyl-2-(2-methoxyethyl)-2,6-dihydro-7h-pyrazolo[4,3-d]pyrimidin-7-one

HRID 354174Notes

Reaction equation

HRID 354174 reaction equation
[Cl-].[Li+].[CH2:3]([O:7][C:8]1[C:13]([C:14]2[NH:15][C:16](=[O:29])[C:17]3[C:18](=[C:20]([CH2:27][CH3:28])[N:21]([CH2:23][CH2:24][O:25][CH3:26])[N:22]=3)[N:19]=2)=[CH:12][C:11](I)=[CH:10][N:9]=1)[CH2:4][CH2:5][CH3:6]>O1CCOCC1.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>[CH2:3]([O:7][C:8]1[C:13]([C:14]2[NH:15][C:16](=[O:29])[C:17]3[C:18](=[C:20]([CH2:27][CH3:28])[N:21]([CH2:23][CH2:24][O:25][CH3:26])[N:22]=3)[N:19]=2)=[CH:12][C:11]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=2)=[CH:10][N:9]=1)[CH2:4][CH2:5][CH3:6]

Participants

5

Reactant 2

HCID 433294Lithium ChlorideHCID 1354560315-(2-Butoxy-5-iodo-3-pyridinyl)-3-ethyl-2-(2-methoxyethyl)-2,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one

Product 1

HCID 1357305785-(2-Butoxy-5-[2-pyridyl]-3-pyridinyl)-3-ethyl-2-(2-methoxyethyl)-2,6-dihydro-7h-pyrazolo[4,3-d]pyrimidin-7-oneYield 58%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

2-Tributyltin pyridine (192 mg, 0.52 mmol), lithium chloride (170 mg, 4.00 mmol), cuprous iodide (11.5 mg, 0.06 mmol), Pd(PPh3)4 (46.5 mg, 0.04 mmol) and the title compound of Example 1 (200 mg, 0.40 mmol) were stirred together in dioxan (10 mL) under a nitrogen atmosphere. The mixture was heated at reflux for 3.5 h, allowed to cool and the solvent removed in vacuo. The residue was taken up in ethyl acetate and shaken vigorously with 5% aqueous potassium fluoride solution for 10 min and the mixture filtered through Arbocel®. The organic layer was separated, washed with 5% aqueous potassium fluoride solution, saturated sodium bicarbonate solution and brine. The organics were dried (MgSO4) and concentrated. The solid was partially purified by trituration with cold ethyl acetate and further purified by flash column chromatography (elution with 50:1 dichloromethane/methanol) to give the title compound (52 mg, 29%).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 3.5 h
  3. temperatureto cool
  4. customthe solvent removed in vacuo
  5. filtrationthe mixture filtered through Arbocel®
  6. customThe organic layer was separated
  7. washwashed with 5% aqueous potassium fluoride solution, saturated sodium bicarbonate solution and brine
  8. dry with materialThe organics were dried (MgSO4)
  9. concentrationconcentrated
  10. customThe solid was partially purified by trituration with cold ethyl acetate
  11. customfurther purified by flash column chromatography (elution with 50:1 dichloromethane/methanol)

Sources & evidence

ORD record
ord-e44a27c4d98f44749fc9b11962c5f8e3
Source dataset
uspto-grants-2004_06
Patent number
US06756373B1

Reaction notes

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