3,5-Dimethylisoxazole-4-boronic acid pinacol ester → HCID 46205511, compound

HRID 1620404Notes

Reaction equation

HRID 1620404 reaction equation
[CH3:1][C:2]1[C:6](B2OC(C)(C)C(C)(C)O2)=[C:5]([CH3:16])[O:4][N:3]=1.Cl[C:18]1[C:23]2[CH:24]=[CH:25][C:26]([NH:28][C:29]3[CH:34]=[CH:33][C:32]([F:35])=[CH:31][C:30]=3[F:36])=[N:27][C:22]=2[CH:21]=[N:20][N:19]=1>O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+].CCOC(C)=O.O.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>[F:36][C:30]1[CH:31]=[C:32]([F:35])[CH:33]=[CH:34][C:29]=1[NH:28][C:26]1[CH:25]=[CH:24][C:23]2[C:18]([C:6]3[C:2]([CH3:1])=[N:3][O:4][C:5]=3[CH3:16])=[N:19][N:20]=[CH:21][C:22]=2[N:27]=1

Participants

8

Reactant 2

HCID 27586563,5-Dimethylisoxazole-4-boronic acid pinacol esterHCID 86664561HCID 86664561, compound

Product 1

HCID 46205511HCID 46205511, compound

Reagents, catalysts & solvents 5

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 10340Sodium CarbonateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoxazole (252 mg, 1.12 mmol), 5-chloro-N-(2,4-difluorophenyl)pyrido[3,2-d]pyridazin-2-amine (300 mg, 1.02 mmol) and tetrakis (36 mg, 31 μmol) in 4.0 mL of dioxane and sodium carbonate (2.0 mL of 1 N solution) was heated in a microwave at 130° C. for 35 min. It was diluted with 10 mL of EtOAc and 2.0 mL water and extracted. An additional extraction with DCM (15 mL) was done. The combined extracts and an insoluble tan solid were dried over MgSO4. Filtration through a sintered glass frit washing with 1:1 MeOH:DCM resulted in complete solubilization of the tan solid. The solution was concentrated and washed with Et2O (2×15 mL), EtOAc (15 mL) and hexanes (2×15 mL) to afford a tan amorphous solid which was purified on the ISCO to afford the title compound as a yellow amorphous solid. MS (ESI, pos.ion) m/z: M+1=354.0

Workup

  1. extractionextracted
  2. extractionAn additional extraction with DCM (15 mL)
  3. dry with materialThe combined extracts and an insoluble tan solid were dried over MgSO4
  4. filtrationFiltration through a sintered glass frit
  5. washwashing with 1:1 MeOH
  6. customDCM resulted in complete solubilization of the tan solid
  7. concentrationThe solution was concentrated
  8. washwashed with Et2O (2×15 mL), EtOAc (15 mL) and hexanes (2×15 mL)
  9. customto afford a tan amorphous solid which
  10. customwas purified on the ISCO

Sources & evidence

ORD record
ord-8854f9343b654b46a90c194e5c30a782
Source dataset
uspto-grants-2014_07
Patent number
US08772481B2

Reaction notes

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