5-Bromo-2-fluoropyridine → (2-Amino-5-bromo-pyridin-3-yl)-(6-fluoro-pyridin-3-yl)methanone

HRID 729842

Reaction equation

HRID 729842 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([F:8])=[N:6][CH:7]=1.C([Mg]Cl)(C)C.Cl.[NH2:15][C:16]1[N:27]=[CH:26][C:25]([Br:28])=[CH:24][C:17]=1[C:18](N(OC)C)=[O:19]>C1COCC1>[NH2:15][C:16]1[C:17]([C:18]([C:2]2[CH:7]=[N:6][C:5]([F:8])=[CH:4][CH:3]=2)=[O:19])=[CH:24][C:25]([Br:28])=[CH:26][N:27]=1

Participants

5

Reactant 3

HCID 27831685-Bromo-2-fluoropyridineHCID 86602997N-methoxy-N-methyl-2-amino-5-bromonicotinamide hydrochlorideHCID 178418918HCID 178418918, compound

Product 1

HCID 59699837(2-Amino-5-bromo-pyridin-3-yl)-(6-fluoro-pyridin-3-yl)methanoneYield 49%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of 5-bromo-2-fluoropyridine (5.6 ml, 54.2 mmol) in THF (50 ml) at 0° C. under nitrogen was added dropwise a 2 M solution of iso-propylmagnesium chloride in THF (27 ml) over a period of 10 minutes. The ice bath was removed and the reaction mixture was stirred at room temperature for 2 hours. The resulting slurry was added dropwise via cannula to a solution of 2-amino-5-bromo-N-methoxy-N-methyl-nicotinamide hydrochloride (3.0 g, 11.5 mmol) in THF (50 ml) at room temperature under nitrogen over a period of 30 minutes. After stirring for 3 hours, the reaction was quenched by addition of a saturated aqueous solution of ammonium chloride (50 ml) at 0° C. and the mixture was stirred at room temperature for another 20 minutes. Water was added and the mixture was extracted with ethyl acetate (three times). The combined organic layers were dried over sodium sulfate, then filtered and concentrated. Crystallization from methanol (ca. 60 ml) afforded the title compound as dark yellow crystals (1.48 g, 49% yield). 1H NMR (DMSO-d6): δ 8.49 (s, 1H), 8.34 (d, J=1.5 Hz, 1H), 8.23 (dt, J=2.5, 8.0 Hz, 1H), 7.81 (d, J=2.5 Hz, 1H), 7.74 (broad s, 2H), 7.36 (dd, J=2.0, 8.0 Hz, 1H); MS: m/z 295.9, 297.9 [MH]+.

Workup

  1. customThe ice bath was removed
  2. stirringAfter stirring for 3 hours
  3. customthe reaction was quenched by addition of a saturated aqueous solution of ammonium chloride (50 ml) at 0° C.
  4. stirringthe mixture was stirred at room temperature for another 20 minutes
  5. additionWater was added
  6. extractionthe mixture was extracted with ethyl acetate (three times)
  7. dry with materialThe combined organic layers were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customCrystallization from methanol (ca. 60 ml)

Sources & evidence

ORD record
ord-14852d75fc6c404ea66d1436fbf18997
Source dataset
uspto-grants-2009_09
Patent number
US07582637B2

Linked notes

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