Formaldehyde → 5-{2-Butoxy-5-[3-(dimethylamino)propanoyl]-3-pyridinyl}-3-ethyl-2-(2-methoxyethyl)-2,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one

HRID 354179Notes

Reaction equation

HRID 354179 reaction equation
Cl.[CH3:2][NH:3][CH3:4].C=O.[C:7](OC(=O)C)(=O)C.[C:14]([C:17]1[CH:18]=[C:19]([C:28]2[NH:29][C:30](=[O:43])[C:31]3[C:32](=[C:34]([CH2:41][CH3:42])[N:35]([CH2:37][CH2:38][O:39][CH3:40])[N:36]=3)[N:33]=2)[C:20]([O:23][CH2:24][CH2:25][CH2:26][CH3:27])=[N:21][CH:22]=1)(=[O:16])[CH3:15]>>[CH2:24]([O:23][C:20]1[C:19]([C:28]2[NH:29][C:30](=[O:43])[C:31]3[C:32](=[C:34]([CH2:41][CH3:42])[N:35]([CH2:37][CH2:38][O:39][CH3:40])[N:36]=3)[N:33]=2)=[CH:18][C:17]([C:14](=[O:16])[CH2:15][CH2:2][N:3]([CH3:7])[CH3:4])=[CH:22][N:21]=1)[CH2:25][CH2:26][CH3:27]

Participants

5

Reactant 4

HCID 712FormaldehydeHCID 7918Acetic AnhydrideHCID 10473Dimethylamine, hydrochlorideHCID 1354846345-(5-Acetyl-2-butoxy-3-pyridinyl)-3-ethyl-2-(2-methoxyethyl)-2,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one

Product 1

HCID 1357306455-{2-Butoxy-5-[3-(dimethylamino)propanoyl]-3-pyridinyl}-3-ethyl-2-(2-methoxyethyl)-2,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one

Procedure

Dimethylamine hydrochloride (280 mg, 31 mmol) was added to formaldehyde (72 mg, 2 mL of a 37-41% aqueous solution) and the mixture sonicated until the white solid dissolved. After 30 min acetic anhydride (1.2 mL) was added and the mixture warmed in a water bath until a clear solution was obtained. A portion of this solution (0.16 mL) was added to 5-(5-acetyl-2-butoxy-3-pyridinyl)-3-ethyl-2-(2-methoxyethyl)-2,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one (Example 16) (100 mg, 0.24 mmol) and the resulting solution heated in a water bath. After 1 h the reaction was cooled and extracted from saturated sodium bicarbonate solution with ethyl acetate. The organics were washed with a further portion of sodium bicarbonate solution then brine, dried (MgSO4) and concentrated. The residue was purified by flash column chromatography (gradient elution from 100% dichloromethane to 10% methanol:dichloromethane) to give 50 mg product.

Workup

  1. customsonicated until the white solid
  2. dissolutiondissolved
  3. temperaturethe mixture warmed in a water bath until a clear solution
  4. customwas obtained
  5. temperaturethe resulting solution heated in a water bath
  6. temperatureAfter 1 h the reaction was cooled
  7. extractionextracted from saturated sodium bicarbonate solution with ethyl acetate
  8. washThe organics were washed with a further portion of sodium bicarbonate solution
  9. dry with materialbrine, dried (MgSO4)
  10. concentrationconcentrated
  11. customThe residue was purified by flash column chromatography (gradient elution from 100% dichloromethane to 10% methanol:dichloromethane)

Sources & evidence

ORD record
ord-76d332c5cbd749909c4af1c240d02e4c
Source dataset
uspto-grants-2004_06
Patent number
US06756373B1

Reaction notes

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