Potassium Carbonate → HCID 57912464, compound

HRID 1971792

Reaction equation

HRID 1971792 reaction equation
Br[C:2]1[N:3]2[N:9]=[C:8]([O:10][CH3:11])[C:7]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[C:4]2[S:5][CH:6]=1.[CH:20]1([O:24][CH2:25][C:26]2[CH:31]=[C:30]([O:32][CH3:33])[C:29](B(O)O)=[C:28]([O:37][CH3:38])[CH:27]=2)[CH2:23][CH2:22][CH2:21]1.C(=O)([O-])[O-].[K+].[K+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C.O.COCCOC>[CH:20]1([O:24][CH2:25][C:26]2[CH:27]=[C:28]([O:37][CH3:38])[C:29]([C:2]3[N:3]4[N:9]=[C:8]([O:10][CH3:11])[C:7]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[C:4]4[S:5][CH:6]=3)=[C:30]([O:32][CH3:33])[CH:31]=2)[CH2:23][CH2:22][CH2:21]1

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 57912433(3-Bromo-6-methoxy-pyrazolo[5,1-b]thiazol-7-yl)-carbamic acid tert-butyl esterHCID 57912446{4-[(Cyclobutyloxy)methyl]-2,6-dimethoxyphenyl}boronic acid

Product 1

HCID 57912464HCID 57912464, compoundYield 89.4%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

To a mixture of tert-butyl (3-bromo-6-methoxypyrazolo[5,1-b][1,3]thiazol-7-yl)carbamate (987 mg, 2.83 mmol), DME (80 mL) and water (28 mL) were added {4-[(cyclobutyloxy)methyl]-2,6-dimethoxyphenyl}boronic acid (904 mg, 3.4 mmol), potassium carbonate (785 mg, 5.68 mmol), triphenylphosphine (370 mg, 1.42 mmol) and palladium acetate (63.7 mg, 0.282 mmol) in that order, and the mixture was stirred at 90° C. (internal temperature) for 3 hours. Water was added to the reaction mixture, and then ethyl acetate was added. After thoroughly shaking the mixture, the organic layer was separated and the organic layer was washed with brine and dried over anhydrous magnesium sulfate. The mixture was filtered, and then the solvent in the filtrate was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (mixture of n-heptane and ethyl acetate: n-heptane/ethyl acetate=2/1) to obtain the title compound (1.24 g, 2.53 mmol).

Workup

  1. stirringAfter thoroughly shaking the mixture
  2. customthe organic layer was separated
  3. washthe organic layer was washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationThe mixture was filtered
  6. distillationthe solvent in the filtrate was distilled off under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (mixture of n-heptane and ethyl acetate: n-heptane/ethyl acetate=2/1)

Sources & evidence

ORD record
ord-c00b2c3d15a94d3cbcfc301c34f7af67
Source dataset
uspto-grants-2013_04
Patent number
US08431603B2

Linked notes

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