1,2-Dimethoxyethane → HCID 59334497, compound

HRID 1639867Notes

Reaction equation

HRID 1639867 reaction equation
Br[C:2]1[CH:10]=[CH:9][C:8]2[C:4](=[CH:5][N:6]([CH3:11])[N:7]=2)[C:3]=1[CH:12]1[CH2:14][CH:13]1[CH2:15][NH:16][C:17](=[O:19])[CH3:18].[CH:20]1(B(O)O)[CH2:22][CH2:21]1.C(=O)([O-])[O-].[K+].[K+].COCCOC>C(OCC)(=O)C.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>[CH:20]1([C:2]2[CH:10]=[CH:9][C:8]3[C:4](=[CH:5][N:6]([CH3:11])[N:7]=3)[C:3]=2[CH:12]2[CH2:14][CH:13]2[CH2:15][NH:16][C:17](=[O:19])[CH3:18])[CH2:22][CH2:21]1

Participants

8

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 2760897Cyclopropylboronic acidHCID 59334491HCID 59334491, compound

Product 1

HCID 59334497HCID 59334497, compoundYield 39%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

N-{[2-(5-bromo-2-methyl-2H-indazol-4-yl)cyclopropyl]methyl}acetamide (200 mg, 0.621 mmol) obtained in Example 29, cyclopropylboronic acid (80 mg, 0.931 mmol), potassium carbonate (85.8 mg, 0.621 mmol) and tetrakis(triphenylphosphine)palladium(0) (71.8 mg, 0.062 mmol) were added to a mixed solution of water (0.25 mL) and 1,2-dimethoxyethane (2.75 mL), and the mixture was stirred at 120° C. for 20 min using microwave, thereafter at 130° C. for 40 min. The reaction solution was diluted with ethyl acetate and water, and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (methanol/ethyl acetate=0/100→10/90) and HPLC to give the title compound (68 mg, yield 39%).

Workup

  1. waitat 130° C. for 40 min
  2. extractionthe aqueous layer was extracted with ethyl acetate
  3. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (methanol/ethyl acetate=0/100→10/90) and HPLC

Sources & evidence

ORD record
ord-837f3296cfa14ade86e6d51fab25dc59
Source dataset
uspto-grants-2012_02
Patent number
US08110585B2

Reaction notes

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