Ethyl Acetate → 5-(2-Butoxy-5-iodo-3-pyridinyl)-3-ethyl-2-(2-methoxyethyl)-2,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one

HRID 354169Notes

Reaction equation

HRID 354169 reaction equation
C[Si](C)(C)[N-][Si](C)(C)C.[K+].[NH2:11][C:12]([C:14]1[C:18]([NH:19][C:20](=O)[C:21]2[CH:26]=[C:25]([I:27])[CH:24]=[N:23][C:22]=2[O:28][CH2:29][CH2:30][CH2:31][CH3:32])=[C:17]([CH2:34][CH3:35])[N:16]([CH2:36][CH2:37][O:38][CH3:39])[N:15]=1)=[O:13].C(OCC)(=O)C>C(O)CCC>[CH2:29]([O:28][C:22]1[C:21]([C:20]2[NH:11][C:12](=[O:13])[C:14]3[C:18](=[C:17]([CH2:34][CH3:35])[N:16]([CH2:36][CH2:37][O:38][CH3:39])[N:15]=3)[N:19]=2)=[CH:26][C:25]([I:27])=[CH:24][N:23]=1)[CH2:30][CH2:31][CH3:32]

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 3251421Potassium bis(trimethylsilyl)amideHCID 11785620N-[3-(aminocarbonyl)-5-ethyl-1-(2-methoxyethyl)-1H-pyrazol-4-yl]-2-butoxy-5-iodonicotinamide

Product 1

HCID 1354560315-(2-Butoxy-5-iodo-3-pyridinyl)-3-ethyl-2-(2-methoxyethyl)-2,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-oneYield 42.3%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

Potassium hexamethyldisilazide (46 mg, 0.23 mmol) was added to N-[3-(aminocarbonyl)-5-ethyl-1-(2-methoxyethyl)-1H-pyrazol-4-yl]-2-butoxy-5-iodonicotinamide (Preparation 13) (100 mg, 0.19 mmol) in degassed n-butanol (2 mL) and the solution stirred under a nitrogen atmosphere. The reaction was heated at reflux for 9 h and then cooled. The butanol was removed in vacuo and the residue partitioned between dichloromethane and 1N hydrochloric acid. The organic phase was separated and washed with brine, dried (MgSO4) and concentrated to give a white solid. Trituration with ethyl acetate gave the title compound (40 mg, 42%) as a white solid.

Workup

  1. temperatureThe reaction was heated
  2. temperatureat reflux for 9 h
  3. temperaturecooled
  4. customThe butanol was removed in vacuo
  5. customthe residue partitioned between dichloromethane and 1N hydrochloric acid
  6. customThe organic phase was separated
  7. washwashed with brine
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated
  10. customto give a white solid

Sources & evidence

ORD record
ord-fd8b0f42f64540adaf46ab9ef992a53b
Source dataset
uspto-grants-2004_06
Patent number
US06756373B1

Reaction notes

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