1,4-Dioxane → HCID 58825012, compound

HRID 270958Notes

Reaction equation

HRID 270958 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:7]([CH3:22])=[N:8][N:9]2[C:14]([CH:15]3[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]3)=[C:13](Br)[CH:12]=[N:11][C:10]=12)=[O:5])[CH3:2].[F:23][C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>[Pd].C(OCC)(=O)C>[CH2:1]([O:3][C:4]([C:6]1[C:7]([CH3:22])=[N:8][N:9]2[C:14]([CH:15]3[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]3)=[C:13]([C:27]3[CH:28]=[CH:29][C:24]([F:23])=[CH:25][CH:26]=3)[CH:12]=[N:11][C:10]=12)=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 2856454-Fluorophenylboronic acidHCID 58825042HCID 58825042, compound

Product 1

HCID 58825012HCID 58825012, compoundYield 94%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 187 mg (0.5 mmol) of 6-bromo-7-cyclohexyl-2-methyl-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid ethyl ester, 105 mg (0.75 mmol, 1.5 equiv) of 4-fluorophenylboronic acid, 20 mg (0.025 mmol, 5 mol %) of Pd catalyst, and 318 mg (1.5 mmol, 3 equiv) of potassium phosphate was placed into a carousel tube. After a vacuum and argon cycle, 1,4-dioxane (7 mL) was added, and the resulting mixture was heated at 80° C. under argon for 14 h. The reaction mixture was diluted with ethyl acetate, filtered through a small pad of Celite, dried over sodium sulfate and evaporated to give a brown residue which was chromatographed on silica gel (gradient elution with 2%, 5% to 10% ethyl acetate in dichloromethane) to afford 0.178 g (94%) of 7-cyclohexyl-6-(4-fluoro-phenyl)-2-methyl-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid ethyl ester as an off-white solid as indicated by 1H NMR; LC-MS—calcd for C22H24FN3O2 [M++H]+: 382.19, found: 382.1.

Workup

  1. customwas placed into a carousel tube
  2. filtrationfiltered through a small pad of Celite
  3. dry with materialdried over sodium sulfate
  4. customevaporated
  5. customto give a brown residue which
  6. customwas chromatographed on silica gel (gradient elution with 2%, 5% to 10% ethyl acetate in dichloromethane)

Sources & evidence

ORD record
ord-794e5c4020e044ffbc5ae33ce9e6cc64
Source dataset
uspto-grants-2008_11
Patent number
US07449488B2

Reaction notes

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