Potassium Carbonate → Tert-butyl[3-(4-cyano-2,6-dimethoxyphenyl)-6-methoxypyrazolo[5,1-b][1,3]thiazol-7-yl]carbamate

HRID 1971785Notes

Reaction equation

HRID 1971785 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.[C:20]([C:22]1[CH:27]=[C:26]([O:28][CH3:29])[C:25](B(O)O)=[C:24]([O:33][CH3:34])[CH:23]=1)#[N:21].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.CCCCCCC.C(OCC)(=O)C.C(OCC)(=O)C.O.COCCOC>[C:15]([O:14][C:13](=[O:19])[NH:12][C:7]1[C:8]([O:10][CH3:11])=[N:9][N:3]2[C:2]([C:25]3[C:24]([O:33][CH3:34])=[CH:23][C:22]([C:20]#[N:21])=[CH:27][C:26]=3[O:28][CH3:29])=[CH:6][S:5][C:4]=12)([CH3:18])([CH3:17])[CH3:16]

Participants

10

Reactant 4

HCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 57912433(3-Bromo-6-methoxy-pyrazolo[5,1-b]thiazol-7-yl)-carbamic acid tert-butyl esterHCID 588166494-Cyano-2,6-dimethoxyphenylboronic acid

Product 1

HCID 44478735Tert-butyl[3-(4-cyano-2,6-dimethoxyphenyl)-6-methoxypyrazolo[5,1-b][1,3]thiazol-7-yl]carbamateYield 51.7%

Reagents, catalysts & solvents 5

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolventHCID 21899848Ethylacetate heptaneSolvent

Conditions

Temperature
90 °C

Procedure

To a mixture of tert-butyl (3-bromo-6-methoxypyrazolo[5,1-b][1,3]thiazol-7-yl)carbamate (461 mg, 1.33 mmol), DME (49 mL) and water (16 mL) were added (4-cyano-2,6-dimethoxyphenyl)boronic acid (412 mg, 2.00 mmol), potassium carbonate (366 mg, 2.66 mmol), triphenylphosphine (174 mg, 0.659 mmol) and palladium acetate (29.8 mg, 0.132 mmol) in that order, and the mixture was stirred at 90° C. (internal temperature) for 2 hours. Water was added to the 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 then 1/1) to obtain the title compound (296 mg, 0.688 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 (
  8. additionmixture of n-heptane and ethyl acetate

Sources & evidence

ORD record
ord-27290163f36f4e06baf6d91a43d803f0
Source dataset
uspto-grants-2013_04
Patent number
US08431603B2

Reaction notes

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