3,5-Dibromopyridine → HCID 89486961, compound

HRID 510186Notes

Reaction equation

HRID 510186 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Br:8])[CH:7]=1.[NH:9]1[CH2:13][CH2:12][CH2:11][CH:10]1[C:14]1[S:15][CH:16]=[CH:17][N:18]=1.CC(C)([O-])C.[Na+].C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>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]>[Br:8][C:6]1[CH:5]=[N:4][CH:3]=[C:2]([N:9]2[CH2:13][CH2:12][CH2:11][CH:10]2[C:14]2[S:15][CH:16]=[CH:17][N:18]=2)[CH:7]=1

Participants

7

Reactant 4

HCID 693693,5-DibromopyridineHCID 634876Binap, (A+-)-HCID 33580902-(2-Pyrrolidinyl)-1,3-thiazoleHCID 23676156Sodium t-butoxide

Product 1

HCID 89486961HCID 89486961, compoundYield 79.6%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

To a nitrogen degassed mixture of 3,5-dibromopyridine (4.61 g, 19.45 mmol), 2-(pyrrolidin-2-yl)thiazole (CA, 1.0 g, 6.48 mmol) and sodium t-butoxide (1.246 g, 12.97 mmol), in Toluene (20 ml) was added binap (0.807 g, 1.297 mmol) and tris(dibenzylideneacetone)di-palladium(0) (0.594 g, 0.648 mmol). The reaction was sealed and heated at 90° C. for 30 min. The reaction was cooled, quenched into water (100 mL), aqueous KHSO4 (20 mL) and ethyl acetate (200 mL) added. Aqueous NaHCO3 was added to adjust pH basic and ethyl acetate layer removed. Aqueous extract washed with ethyl acetate (50 mL) and the organic extracts washed with brine (50 mL), dried over sodium sulfate and concentrated to oil. The oil was chromatographed on silica using 25-75% ethyl acetate/hexanes to give 1.6 g foam of 1-7.

Workup

  1. customTo a nitrogen degassed
  2. customThe reaction was sealed
  3. temperatureThe reaction was cooled
  4. customquenched into water (100 mL), aqueous KHSO4 (20 mL) and ethyl acetate (200 mL)
  5. additionadded
  6. additionAqueous NaHCO3 was added
  7. customethyl acetate layer removed
  8. extractionAqueous extract
  9. washwashed with ethyl acetate (50 mL)
  10. washthe organic extracts washed with brine (50 mL)
  11. dry with materialdried over sodium sulfate
  12. concentrationconcentrated to oil
  13. customThe oil was chromatographed on silica using 25-75% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-3fbbf9ff9ecc4e0aa41a930fd152e9ad
Source dataset
uspto-grants-2015_08
Patent number
US09096598B2

Reaction notes

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