Potassium Hydroxide → Allyl 2-amino-5-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine-3-carboxylate

HRID 1850673Notes

Reaction equation

HRID 1850673 reaction equation
O1CCO[CH:2]1[CH2:6][C:7](=O)[C:8]([F:11])([F:10])[F:9].[NH2:13][C:14]1[C:18]([C:19]([O:21][CH2:22][CH:23]=[CH2:24])=[O:20])=[C:17]([NH2:25])[NH:16][N:15]=1.[OH-].[K+]>O1CCOCC1>[NH2:25][C:17]1[C:18]([C:19]([O:21][CH2:22][CH:23]=[CH2:24])=[O:20])=[C:14]2[N:13]=[C:7]([C:8]([F:9])([F:10])[F:11])[CH:6]=[CH:2][N:15]2[N:16]=1

Participants

5

Reactant 3

HCID 14797Potassium HydroxideHCID 552960491-(1,3-Dioxolane-2-yl)-3,3,3-trifluoropropane-2-oneHCID 73554792Allyl 3,5-diamino-1H-pyrazole-4-carboxylate

Product 1

HCID 90417814Allyl 2-amino-5-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine-3-carboxylateYield 79%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

3-(1,3-Dioxolan-2-yl)-1,1,1-trifluoro-propan-2-one (55.58 g, 301.9 mmol) and allyl 3,5-diamino-1H-pyrazole-4-carboxylate (55 g, 301.9 mmol) were dissolved in 1,4-dioxane (330 mL). KOH (1.694 g, 30.19 mmol) was added and the yellow suspension was stirred at room temperature for 4 h30 min. The reaction mixture was heated at 90° C. for 16 h. The mixture was cooled down to room temperature. The reaction mixture was concentrated onto silica and purified by column chromatography (CombiFlash Companion XL, 1.5 kg column, 0.5 to 40% EtOAc in DCM) to afford allyl 2-amino-5-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine-3-carboxylate 4d as a bright yellow solid (68 g, 79% yield).

Workup

  1. temperatureThe reaction mixture was heated at 90° C. for 16 h
  2. temperatureThe mixture was cooled down to room temperature
  3. concentrationThe reaction mixture was concentrated onto silica
  4. custompurified by column chromatography (CombiFlash Companion XL, 1.5 kg column, 0.5 to 40% EtOAc in DCM)

Sources & evidence

ORD record
ord-e981510f0ee84801ad9bbeebee7ef5cc
Source dataset
uspto-grants-2015_02
Patent number
US08957078B2

Reaction notes

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