Potassium Carbonate → HCID 67120058, compound

HRID 1410163Notes

Reaction equation

HRID 1410163 reaction equation
Br[C:2]1[C:3]([C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)=[N:4][N:5]([CH3:17])[C:6]=1[CH2:7][CH2:8][O:9][Si:10]([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11].[CH3:26][C:27]1[C:31](B(O)O)=[C:30]([CH3:35])[O:29][N:28]=1.C([O-])([O-])=O.[K+].[K+]>COCCOC.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>[Si:10]([O:9][CH2:8][CH2:7][C:6]1[N:5]([CH3:17])[N:4]=[C:3]([C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)[C:2]=1[C:31]1[C:27]([CH3:26])=[N:28][O:29][C:30]=1[CH3:35])([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27343463,5-Dimethylisoxazole-4-boronic acid2×HCID 68178484HCID 68178484, compound

Product 1

HCID 67120058HCID 67120058, compoundYield 24%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of 4-bromo-5-(2-(tert-butyldimethylsilyloxy)ethyl)-3-(4-methoxyphenyl)-1-methyl-1-H-pyrazole (140 mg, 0.33 mmol), 3,5-dimethylisoxazol-4-ylboronic acid (92.8 mg, 0.66 mmol), K2CO3 (328 mg, 2.37 mmol) and Pd(PPh3)4 (19.0 mg, 0.02 mmol) in DME (1 mL) and water (1 mL) was flushed with argon and irradiated in the microwave at 140° C. for 20 min. Full conversion was not achieved. The mixture was filtered to remove palladium black. Irradiation in the microwave was continued until full conversion was achieved. Altogether 3,5-dimethylisoxazol-4-ylboronic acid (233 mg, 1.66 mmol) and Pd(PPh3)4 (57.0 mg, 0.06 mmol) were used and three irradiations were run. Water was added and the crude mixture was extracted with EtOAc. Purification on silica gel gave 4-(5-(2-(tert-butyldimethylsilyloxy)ethyl)-3-(4-methoxyphenyl)-1-methyl-1H-pyrazol-4-yl)-3,5-dimethylisoxazole (34.4 mg, 0.078 mmol, 24%).

Workup

  1. customwas flushed with argon
  2. customirradiated in the microwave at 140° C. for 20 min
  3. filtrationThe mixture was filtered
  4. customto remove palladium black
  5. customIrradiation in the microwave
  6. extractionthe crude mixture was extracted with EtOAc
  7. customPurification on silica gel

Sources & evidence

ORD record
ord-b2c0792ba3324dbd806b2f7fb9d03753
Source dataset
uspto-grants-2014_12
Patent number
US08921402B2

Reaction notes

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