1-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole → HCID 59803819, compound

HRID 253447Notes

Reaction equation

HRID 253447 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:10]([CH2:11][C:12]3[C:28]([F:29])=[CH:27][C:15]([O:16]CC4NC5C=CC=CC=5N=4)=[C:14]([F:30])[CH:13]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[CH3:31][N:32]1[CH:36]=[C:35](B2OC(C)(C)C(C)(C)O2)[CH:34]=[N:33]1>C(#N)C.C(=O)([O-])[O-].[K+].[K+].O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:30][C:14]1[CH:13]=[C:12]([CH2:11][C:10]2[C:4]3[C:5](=[N:6][CH:7]=[C:2]([C:35]4[CH:34]=[N:33][N:32]([CH3:31])[CH:36]=4)[CH:3]=3)[NH:8][CH:9]=2)[C:28]([F:29])=[CH:27][C:15]=1[OH:16]

Participants

7

Reactant 2

HCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 24956294HCID 24956294, compound

Product 1

HCID 59803819HCID 59803819, compound

Reagents, catalysts & solvents 4

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolvent2×HCID 6342AcetonitrileSolventHCID 11430Potassium CarbonateSolvent

Conditions

Temperature
160 °C

Procedure

To 2-[4-(5-bromo-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-2,5-difluoro-phenoxymethyl]-1H-benzoimidazole (P-2107, 25.0 m g, 0.053 mmol, prepared as described in Example 41) in acetonitrile (4.00 mL) and 1M potassium carbonate in water (2.00 mL), 1-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (13.3 mg, 0.064 mmol) and tetrakis(triphenylphosphine)-palladium(0) (10.0 mg, 8.65E-3 mmol) were added. The reaction was heated to 160° C. for 20 minutes in a CEM Discover microwave instrument. The reaction was poured into water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography eluting with 20% to 100% ethyl acetate in hexane to give a white solid (P-2161, 5.4 mg, 29.8%). MS (ESI) [M+H+]+=341.2.

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated
  5. custompurified by silica gel column chromatography
  6. washeluting with 20% to 100% ethyl acetate in hexane
  7. customto give a white solid (P-2161, 5.4 mg, 29.8%)

Sources & evidence

ORD record
ord-7123c41347284eed9d0ee2685b45729f
Source dataset
uspto-grants-2011_01
Patent number
US07872018B2

Reaction notes

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