Ethyl 2-formyl-3-oxopropanoate → Ethyl 2-(methoxymethyl)pyrazolo[1,5-A]pyrimidine-6-carboxylate

HRID 1393661Notes

Reaction equation

HRID 1393661 reaction equation
[CH:1]([CH:3]([CH:9]=O)[C:4]([O:6][CH2:7][CH3:8])=[O:5])=O.[CH3:11][O:12][CH2:13][C:14]1[CH:15]=[C:16]([NH2:19])[NH:17][N:18]=1>C(O)C>[CH3:11][O:12][CH2:13][C:14]1[CH:15]=[C:16]2[N:19]=[CH:9][C:3]([C:4]([O:6][CH2:7][CH3:8])=[O:5])=[CH:1][N:17]2[N:18]=1

Participants

4

Reactant 2

HCID 11029955Ethyl 2-formyl-3-oxopropanoateHCID 178494541HCID 178494541, compound

Product 1

HCID 23091928Ethyl 2-(methoxymethyl)pyrazolo[1,5-A]pyrimidine-6-carboxylateYield 69.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Ethyl 2-formyl-3-oxopropionate (775 mg) was added to a solution of the thus obtained 5-methoxymethyl-2H-pyrazol-3-ylamine (684 mg) in ethanol (50 ml), and stirred overnight. The reaction solution was concentrated under reduced pressure, and a saturated sodium bicarbonate solution was added to the residue which were then extracted with ethyl acetate. The organic phase was washed with a saturated saline solution and dried over sodium sulfate anhydrous. The resulting product was concentrated under reduced pressure, and the residue was purified by column chromatography (eluting solvent; n-hexane:ethyl acetate 4:1) to give ethyl 2-methoxymethylpyrazolo[1,5-a]pyrimidine-6-carboxylate (878 mg, Y.:69%). 1 M Boron tribromide solution in dichloromethane (0.51 ml) was added dropwise at −70° C. to a solution of the thus obtained ethyl 2-methoxymethylpyrazolo[1,5-a]pyrimidine-6-carboxylate (20 mg) in dichloromethane (2 ml). The temperature of the mixture under stirring was increased from −70° C. to −50° C. over 4.5 hours and then increased from −50° C. to room temperature over 2 hours. The reaction mixture was cooled to 0° C., water was added to the reaction mixture which was then extracted with ethyl acetate, and the extract was dried over sodium sulfate anhydrous. The resulting product was concentrated under reduced pressure to give ethyl 2-hydroxymethylpyrazolo[1,5-a]pyrimidine-6-carboxylate (19 mg, Y.:quant.).

Workup

  1. concentrationThe reaction solution was concentrated under reduced pressure
  2. additiona saturated sodium bicarbonate solution was added to the residue which
  3. extractionwere then extracted with ethyl acetate
  4. washThe organic phase was washed with a saturated saline solution
  5. dry with materialdried over sodium sulfate anhydrous
  6. concentrationThe resulting product was concentrated under reduced pressure
  7. customthe residue was purified by column chromatography (eluting solvent; n-hexane:ethyl acetate 4:1)

Sources & evidence

ORD record
ord-20d4f5a1a3b54cfbbc1a509562c10a6b
Source dataset
uspto-grants-2008_03
Patent number
US07345180B2

Reaction notes

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