3,5-Dibromopyridine → HCID 117628625, compound

HRID 510185Notes

Reaction equation

HRID 510185 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Br:8])[CH:7]=1.Cl.[CH3:10][CH:11]1[NH:16][CH2:15][CH2:14][N:13]2[C:17]([C:20]([F:23])([F:22])[F:21])=[CH:18][N:19]=[C:12]12.CC(C)([O-])C.[Na+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=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:7]=[C:2]([N:16]2[CH2:15][CH2:14][N:13]3[C:17]([C:20]([F:23])([F:21])[F:22])=[CH:18][N:19]=[C:12]3[CH:11]2[CH3:10])[CH:3]=[N:4][CH:5]=1

Participants

7

Reactant 4

HCID 693693,5-DibromopyridineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 117628471HCID 117628471, compound

Product 1

HCID 117628625HCID 117628625, compoundYield 47.5%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

To a nitrogen degassed mixture of 3,5-dibromopyridine (294 mg, 1.242 mmol), 8-methyl-3-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine hydrochloride (CA, 100 mg, 0.414 mmol) and sodium t-butoxide (119 mg, 1.242 mmol), in Toluene (2 ml) was added BINAP (51.5 mg, 0.083 mmol) and tris(dibenzylideneacetone)dipalladium(0) (37.9 mg, 0.041 mmol). The reaction was sealed and heated at 90° C. for ½ hrs. LCMS (215 nM) showed the reaction complete. The reaction was cooled, quenched into water (10 mL) and aqueous. KHSO4 (2 mL) and ethyl acetate (25 mL) added. Aqueous NaHCO3 was added to adjust pH to 7.5 and the ethyl acetate layer removed. Aqueous layer washed with ethyl acetate (25 mL) and organic extracted combined, washed with brine (10 mL), dried over sodium sulfate and concentrated to an oil. Oil chromatographed on silica using 25-70% ethyl acetate/hexanes to give 71 mg product, I-6, as a foam.

Workup

  1. customTo a nitrogen degassed
  2. customThe reaction was sealed
  3. temperatureThe reaction was cooled
  4. customquenched into water (10 mL)
  5. additionKHSO4 (2 mL) and ethyl acetate (25 mL) added
  6. additionAqueous NaHCO3 was added
  7. customthe ethyl acetate layer removed
  8. washAqueous layer washed with ethyl acetate (25 mL)
  9. extractionorganic extracted
  10. washwashed with brine (10 mL)
  11. dry with materialdried over sodium sulfate
  12. concentrationconcentrated to an oil
  13. customOil chromatographed on silica using 25-70% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-003b56d8a1ea42e495d5e6e4b8792e02
Source dataset
uspto-grants-2015_08
Patent number
US09096598B2

Reaction notes

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