Potassium Carbonate → 2-[3-{[(Tert-butoxycarbonyl)amino]methyl}-2-isobutyl-4-(4-methylphenyl)-6-quinolinyl]-1,3-thiazole-4-carboxylic acid

HRID 1986457Notes

Reaction equation

HRID 1986457 reaction equation
[CH2:1]([C:5]1[C:14]([CH2:15][NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[C:13]([C:24]2[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][CH:25]=2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10](OS(C(F)(F)F)(=O)=O)[CH:11]=2)[N:6]=1)[CH:2]([CH3:4])[CH3:3].[B].[C:40]([O-:43])(=[O:42])[CH3:41].[K+].Cl[C:46]1[S:47][CH:48]=C[N:50]=1.C(=O)([O-])[O-].[K+].[K+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].ClCCl.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.O.C1(C)C=CC=CC=1.C(O)C.CS(C)=O>[C:19]([O:18][C:17]([NH:16][CH2:15][C:14]1[C:5]([CH2:1][CH:2]([CH3:3])[CH3:4])=[N:6][C:7]2[C:12]([C:13]=1[C:24]1[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][CH:25]=1)=[CH:11][C:10]([C:46]1[S:47][CH:48]=[C:41]([C:40]([OH:43])=[O:42])[N:50]=1)=[CH:9][CH:8]=2)=[O:23])([CH3:20])([CH3:21])[CH3:22]

Participants

12

Reactant 5

HCID 11430Potassium CarbonateHCID 764292-ChlorothiazoleHCID 517044Potassium AcetateHCID 5462311BoronHCID 510503433-{[(Tert-butoxycarbonyl)amino]methyl}-2-isobutyl-4-(4-methylphenyl)quinolin-6-yl trifluoromethanesulfonate

Product 1

HCID 688291742-[3-{[(Tert-butoxycarbonyl)amino]methyl}-2-isobutyl-4-(4-methylphenyl)-6-quinolinyl]-1,3-thiazole-4-carboxylic acidYield 36%

Reagents, catalysts & solvents 6

HCID 178418397HCID 178418397, compoundCatalystHCID 178418807HCID 178418807, compoundCatalystHCID 679Dimethyl SulfoxideSolventHCID 702EthanolSolventHCID 962WaterSolvent3×HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of tert-butyl [2-isobutyl-4-(4-methylphenyl)-6-trifluoromethanesulfonyloxy-quinolin-3-yl]methylcarbamate (0.50 g, 0.90 mmol), boron bispinacolate (0.25 g, 1.0 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium-dichloromethane (1:1) complex (0.020 g, 0.027 mmol), potassium acetate (0.27 g, 2.7 mmol) and dimethyl sulfoxide (20 ml) was stirred under an argon atmosphere at 100° C. for 15 min. The reaction mixture was poured into water and extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and a mixture of the residue, 2-chlorothiazole (0.17 g, 0.90 mmol), tetrakis(triphenylphosphine)palladium (0.10 g, 0.090 mmol), potassium carbonate (0.63 g, 4.5 mmol), ethanol (4 ml), toluene (20 ml) and water (4 ml) was stirred under an argon atmosphere at 100° C. for 17 hrs. The reaction mixture was poured into water and extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography. The obtained mixture was dissolved in tetrahydrofuran-methanol (1:1, 8 ml) and 1N aqueous sodium hydroxide solution (2 ml) was added. The mixture was stirred at room temperature for 15 min. 1N Hydrochloric acid (50 ml) was added to the reaction mixture and the mixture was extracted with ethyl acetate-tetrahydrofuran (1:1, 100 ml). The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography to give 2-[3-{[(tert-butoxycarbonyl)amino]methyl}-2-isobutyl-4-(4-methylphenyl)quinolin-6-yl]-1,3-thiazole-4-carboxylic acid (0.17 g, yield 36%) as pale-yellow crystals.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe extract was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. stirringwas stirred under an argon atmosphere at 100° C. for 17 hrs
  6. extractionextracted with ethyl acetate
  7. washThe extract was washed with saturated brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. customThe solvent was evaporated under reduced pressure
  10. customthe residue was purified by silica gel column chromatography
  11. dissolutionThe obtained mixture was dissolved in tetrahydrofuran-methanol (1:1, 8 ml)
  12. addition1N aqueous sodium hydroxide solution (2 ml) was added
  13. stirringThe mixture was stirred at room temperature for 15 min
  14. addition1N Hydrochloric acid (50 ml) was added to the reaction mixture
  15. extractionthe mixture was extracted with ethyl acetate-tetrahydrofuran (1:1, 100 ml)
  16. washThe extract was washed with saturated brine
  17. dry with materialdried over anhydrous magnesium sulfate
  18. customThe solvent was evaporated under reduced pressure
  19. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-6ca0e579954d4521afad167e0305055f
Source dataset
uspto-grants-2009_06
Patent number
US07547710B2

Reaction notes

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