Cesium fluoride → 1-tert-Butyl-3-cyclobutyl-5-(3,5-dichloro-phenyl)-1,7-dihydro-pyrazolo[3,4-b]pyridin-6-one

HRID 1594036Notes

Reaction equation

HRID 1594036 reaction equation
Br[C:2]1[C:7](=[O:8])[NH:6][C:5]2[N:9]([C:16]([CH3:19])([CH3:18])[CH3:17])[N:10]=[C:11]([CH:12]3[CH2:15][CH2:14][CH2:13]3)[C:4]=2[CH:3]=1.[Cl:20][C:21]1[CH:22]=[C:23](B(O)O)[CH:24]=[C:25]([Cl:27])[CH:26]=1.[F-].[Cs+]>C(COC)OC.C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:16]([N:9]1[C:5]2[NH:6][C:7](=[O:8])[C:2]([C:23]3[CH:22]=[C:21]([Cl:20])[CH:26]=[C:25]([Cl:27])[CH:24]=3)=[CH:3][C:4]=2[C:11]([CH:12]2[CH2:15][CH2:14][CH2:13]2)=[N:10]1)([CH3:19])([CH3:18])[CH3:17]

Participants

7

Reactant 3

HCID 25953Cesium fluoride2×HCID 27343313,5-Dichlorophenylboronic acid2×HCID 1363386415-Bromo-1-tert-butyl-3-cyclobutyl-1,7-dihydro-pyrazolo[3,4-b]pyridin-6-one

Product 1

HCID 1363386401-tert-Butyl-3-cyclobutyl-5-(3,5-dichloro-phenyl)-1,7-dihydro-pyrazolo[3,4-b]pyridin-6-oneYield 12%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a stirring solution of 5-bromo-1-tert-butyl-3-cyclobutyl-1,7-dihydro -pyrazolo[3,4-b]pyridin-6-one (50.0 mg, 0.15 mmol) in dimethoxyethane (1.5 mL) was added 3,5-dichlorophenyl-boronic acid (32.6 mg, 0.17 mmol), followed by cesium fluoride (51.9 mg, 0.34 mmol), and Pd(PPh3)4 (catalytic amount, 0.005 mmol). The reaction mixture was heated to reflux. After 3 hr, additional amounts of 3,5-dichlorophenyl-boronic acid (32.6 mg, 0.17 mmol), cesium fluoride (51.9 mg, 0.34 mmol), and Pd(PPh3)4 (catalytic amount, 0.005 mmol) were added. After a total of 18 hr, the reaction was cooled to room temperature, diluted with CH2Cl2 and washed with water. The organic layer was dried over MgSO4, filtered through a fritted funnel, and concentrated under reduced pressure. Purification of the resulting material was accomplished by flash chromatography with a Biotage® column, eluting with 5% EtOAc/toluene. The product-containing fractions were collected and concentrated to give the title compound (7.0 mg, 12% yield). LRMS m/z (APCl) 390. 392(M+1).

Workup

  1. temperatureThe reaction mixture was heated to reflux
  2. washwashed with water
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered through a fritted funnel
  5. concentrationconcentrated under reduced pressure
  6. customPurification of the resulting material
  7. washeluting with 5% EtOAc/toluene
  8. customThe product-containing fractions were collected
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-4c50edfb688745e7bb013f4321e67de3
Source dataset
uspto-grants-2007_11
Patent number
US07300943B2

Reaction notes

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