Potassium Carbonate → (4-Pyrazolo[1,5-b]pyridazin-3-ylphenyl)acetic acid

HRID 474140

Reaction equation

HRID 474140 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:14]=[CH:13][C:12]([CH2:15][C:16]([OH:18])=[O:17])=[CH:11][CH:10]=2)O1.Br[C:21]1[CH:22]=[N:23][N:24]2[C:29]=1[CH:28]=[CH:27][CH:26]=[N:25]2.C(=O)([O-])[O-].[K+].[K+]>CC#N.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1>[N:23]1[N:24]2[N:25]=[CH:26][CH:27]=[CH:28][C:29]2=[C:21]([C:9]2[CH:10]=[CH:11][C:12]([CH2:15][C:16]([OH:18])=[O:17])=[CH:13][CH:14]=2)[CH:22]=1

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 37190022-(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetic AcidHCID 529880243-Bromopyrazolo(1,5-b)pyridazine

Product 1

HCID 59535942(4-Pyrazolo[1,5-b]pyridazin-3-ylphenyl)acetic acidYield 72%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of 1.00 g (3.82 mmol) [4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]acetic acid in 5.70 ml CH3CN and 3.80 ml water was added 0.76 g (3.82 mmol) 3-bromopyrazolo[1,5-b]pyridazine, 8.57 mg (0.038 mmol) palladium acetate, 1.21 g (8.77 mmol) potassium carbonate, and 0.031 g (0.076 mmol) SPhos. The resulting suspension was degassed for 5 minutes. After 30 min in the microwave at 150° C., the reaction mixture was cooled, acidified with 1N HCl, extracted with ethyl acetate, and washed with brine. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo. Purification by flash chromatography (silica gel, linear gradient 50-100% EtOAc in hexanes) afforded 0.69 g (72%) (4-pyrazolo[1,5-b]pyridazin-3-ylphenyl)acetic acid. 1H NMR (CD3OD, 400 MHz) 8.40 (dd, J=1.83, 15.75 Hz, 1H); 8.40 (m, 1H); 8.28 (s, 1H); 7.62 (d, J=8.05 Hz, 2H); 7.41 (d, J=7.97 Hz, 2H); 7.22 (dd, J=4.4, 9.1 Hz, 1H); 3.66 (s, 2H). ES-MS M+1=254.1.

Workup

  1. customThe resulting suspension was degassed for 5 minutes
  2. temperaturethe reaction mixture was cooled
  3. extractionextracted with ethyl acetate
  4. washwashed with brine
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification by flash chromatography (silica gel, linear gradient 50-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-2c2f6a5a0b39430b86692d9ef40f1ed5
Source dataset
uspto-grants-2014_01
Patent number
US08637513B2

Linked notes

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