Toluene → tert-Butyl[3-[2,6-dimethoxy-4-(methoxymethyl)phenyl]-6-methyl-2-(methylthio)pyrazolo[5,1-b][1,3]thiazol-7-yl]carbamate

HRID 41271

Reaction equation

HRID 41271 reaction equation
[C:1]([O:5][C:6](=[O:20])[NH:7][C:8]1[C:9]([CH3:19])=[N:10][N:11]2[C:15](Br)=[C:14]([S:17][CH3:18])[S:13][C:12]=12)([CH3:4])([CH3:3])[CH3:2].C1(C)C=CC=CC=1.[CH3:28][O:29][C:30]1[CH:35]=[C:34]([CH2:36][O:37][CH3:38])[CH:33]=[C:32]([O:39][CH3:40])[C:31]=1OB(O)O.C(=O)([O-])[O-].[Na+].[Na+]>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.C(OCC)(=O)C.O.C(O)C>[C:1]([O:5][C:6](=[O:20])[NH:7][C:8]1[C:9]([CH3:19])=[N:10][N:11]2[C:15]([C:31]3[C:32]([O:39][CH3:40])=[CH:33][C:34]([CH2:36][O:37][CH3:38])=[CH:35][C:30]=3[O:29][CH3:28])=[C:14]([S:17][CH3:18])[S:13][C:12]=12)([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 230809452,6-Dimethoxy-4-methoxymethylphenylboric acidHCID 58223503HCID 58223503, compound

Product 1

HCID 68166681tert-Butyl[3-[2,6-dimethoxy-4-(methoxymethyl)phenyl]-6-methyl-2-(methylthio)pyrazolo[5,1-b][1,3]thiazol-7-yl]carbamateYield 91.3%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

To a mixture of tert-butyl[3-bromo-6-methyl-2-(methylthio)pyrazolo[5,1-b][1,3]thiazol-7-yl]carbamate (397 mg, 1.03 mmol), toluene (6.8 mL) and ethanol (3.4 mL) were added 2,6-dimethoxy-4-(methoxymethyl)phenylboric acid (349 mg, 1.55 mmol) synthesized by the method described in WO2004/037822, a 1M aqueous solution of sodium carbonate (2.06 mL, 2.06 mmol) and tetrakis(triphenylphosphine)palladium (119 mg, 0.10 mmol) in this order, and the mixture was heated to reflux at 110° C. for three 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 stirred at 75° C. for five hours. Chloroform was added to the reaction mixture, insoluble matters were filtered off, and then the solvent was distilled off under reduced pressure. The residue was purified by medium pressure silica gel column chromatography (n-heptane/ethyl acetate: 33% then 66%) to obtain 450.9 mg (0.94 mmol) of the title compound.

Workup

  1. customsynthesized by the method
  2. customthe organic layer was separated
  3. stirringthe organic layer was stirred at 75° C. for five hours
  4. additionChloroform was added to the reaction mixture, insoluble matters
  5. filtrationwere filtered off
  6. distillationthe solvent was distilled off under reduced pressure
  7. customThe residue was purified by medium pressure silica gel column chromatography (n-heptane/ethyl acetate

Sources & evidence

ORD record
ord-066a6d4ffd9c437e8db80eb335421739
Source dataset
uspto-grants-2013_09
Patent number
US08530504B2

Linked notes

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