2-Bromothiazole → HCID 68181033, compound

HRID 538682Notes

Reaction equation

HRID 538682 reaction equation
[CH2:1]([CH:8]([CH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][NH:21]1)[CH2:9][NH:10][CH:11]1[CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH2:12]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[C:27]1[S:28][CH:29]=[CH:30][N:31]=1.CC([O-])(C)C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:1]([CH:8]([CH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][NH:21]1)[CH2:9][N:10]([CH:11]1[CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH2:12]1)[C:27]1[S:28][CH:29]=[CH:30][N:31]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 764302-BromothiazoleHCID 23676156Sodium t-butoxideHCID 68181058HCID 68181058, compound

Product 1

HCID 68181033HCID 68181033, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

To a stirred solution of compound 51 (2 g, 5.98 mmol) in dry toluene (35 mL) were added 2-bromo-thiazole (0.53 mL, 5.98 mmol) and NaOtBu (0.805 g, 8.38 mmol) and the solution was degassed with argon for 30 minutes. Pd2 dba3 (0.274 g, 0.30 mmol) and Verkade's super base (0.42 mL, 1.19 mmol) were then added and the resulting mixture was refluxed for 16 hours. The reaction mixture was filtered through a Celite® pad and was washed with ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous Na2SO4, filtered and concentrated. The crude material was purified by Combiflash® chromatography eluting with 20-22% ethyl acetate-hexane to provide compound 52.

Workup

  1. customthe solution was degassed with argon for 30 minutes
  2. temperaturethe resulting mixture was refluxed for 16 hours
  3. filtrationThe reaction mixture was filtered through a Celite® pad
  4. washwas washed with ethyl acetate
  5. washThe organic layer was washed with water and brine
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude material was purified by Combiflash® chromatography
  10. washeluting with 20-22% ethyl acetate-hexane

Sources & evidence

ORD record
ord-3b5ab1a50d78452bae0e0b63015ed758
Source dataset
uspto-grants-2014_10
Patent number
US08865741B2

Reaction notes

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