Potassium Phosphate, Tribasic → 5-Ethyl-4-[6-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl]thiophene-2-carboxylic acid

HRID 1842602Notes

Reaction equation

HRID 1842602 reaction equation
Br[C:2]1[CH:3]=[N:4][N:5]2[CH:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[N:7][C:6]=12.[CH2:15]([C:17]1[S:21][C:20]([C:22]([OH:24])=[O:23])=[CH:19][C:18]=1B1OC(C)(C)C(C)(C)O1)[CH3:16].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:15]([C:17]1[S:21][C:20]([C:22]([OH:24])=[O:23])=[CH:19][C:18]=1[C:2]1[CH:3]=[N:4][N:5]2[CH:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[N:7][C:6]=12)[CH3:16]

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 683041955-Ethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene-2-carboxylic acidHCID 68305187HCID 68305187, compound

Product 1

HCID 683051725-Ethyl-4-[6-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl]thiophene-2-carboxylic acidYield 44.8%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
100 °C

Procedure

3-Bromo-6-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine (165 mg, 0.620 mmol), 5-ethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene-2-carboxylic acid (199 mg, 0.620 mmol), Pd2(dba)3 (56.8 mg, 0.062 mmol), tricyclohexylphosphine (43.5 mg, 0.155 mmol), and 1.27 M potassium phosphate tribasic (aq) (1.65 mL, 2.10 mmol) were placed in a sealed tube and purged with N2 for 5 min. The reaction was heated to 100° C. for 2 h. The reaction was then cooled to room temperature, diluted with water, and extracted with ethyl acetate 3×. The organic layers were combined, washed with brine, dried with sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (10-60% DCM/EtOAc). The fractions were combined and concentrated to give the title compound (95.0 mg, 0.278 mmol). LRMS (APCI) calc'd for (C14H10F3N3O2S) [M+H]+, 342.0; found 341.9.

Workup

  1. custompurged with N2 for 5 min
  2. temperatureThe reaction was then cooled to room temperature
  3. additiondiluted with water
  4. extractionextracted with ethyl acetate 3×
  5. washwashed with brine
  6. dry with materialdried with sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by column chromatography (10-60% DCM/EtOAc)
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-62ad1a2c7daa447fb976238cb344c2ec
Source dataset
uspto-grants-2015_02
Patent number
US08946237B2

Reaction notes

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