1,4-Dioxane → HCID 18445886, compound

HRID 270939Notes

Reaction equation

HRID 270939 reaction equation
[CH:1]1([C:7]2[N:12]3[N:13]=[CH:14][C:15]([C:16]#[N:17])=[C:11]3[N:10]=[CH:9][C:8]=2[C:18]2[CH:23]=[CH:22][C:21](I)=[CH:20][CH:19]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:25][S:26]([C:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1)(=[O:28])=[O:27].P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>[Pd].C(OCC)(=O)C>[CH:1]1([C:7]2[N:12]3[N:13]=[CH:14][C:15]([C:16]#[N:17])=[C:11]3[N:10]=[CH:9][C:8]=2[C:18]2[CH:23]=[CH:22][C:21]([C:32]3[CH:33]=[CH:34][C:29]([S:26]([CH3:25])(=[O:28])=[O:27])=[CH:30][CH:31]=3)=[CH:20][CH:19]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, Tribasic2×HCID 27343644-(Methanesulfonyl)phenylboronic acid2×HCID 18445884HCID 18445884, compound

Product 1

HCID 18445886HCID 18445886, compoundYield 62%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalyst2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 65 mg (0.15 mmol) of 7-cyclohexyl-6-(4-iodo-phenyl)-pyrazolo[1,5-a]pyrimidine-3-carbonitrile, 45 mg (0.225 mmol, 1.5 equiv) of 4-(methanesulfonyl)phenylboronic acid, 6 mg (0.0075 mmol, 5 mol %) of Pd catalyst, and 95 mg (0.45 mmol, 3 equiv) of potassium phosphate was placed into a carousel tube. After a vacuum and argon cycle, 1,4-dioxane (3 mL) was added, and the resulting mixture was heated at 80° C. under argon for 14 h. Since analysis by LC-MS revealed unreacted starting material still present, 45 mg (0.225 mmol, 1.5 equiv) of 4-(methanesulfonyl)phenylboronic acid, 12 mg (0.015 mmol, 10 mol %) of Pd catalyst, and 95 mg (0.45 mmol, 3 equiv) of potassium phosphate was added and heating was continued for 24 h. The reaction mixture was then diluted with ethyl acetate, filtered through a small pad of Celite, dried over sodium sulfate and evaporated to give a brown residue (crude coupling product), which was chromatographed on silica gel (Biotage; gradient elution 2% to 10% ethyl acetate in dichloromethane) to afford 42 mg (62% yield) of desired 7-cyclohexyl-6-(4′-methanesulfonyl-biphenyl-4-yl)-pyrazolo[1,5-a]pyrimidine-3-carbonitrile as indicated by 1H NMR; LC-MS—calcd for C26H24N4O2S [M++H]+: 457.16, found: 457.1.

Workup

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

Sources & evidence

ORD record
ord-83b11ba93c834c2d90cebadd5b03c045
Source dataset
uspto-grants-2008_11
Patent number
US07449488B2

Reaction notes

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