3-Aminopyridine → 5-Bromo-1-methyl-3-(pyridin-3-ylamino)pyrazin-2(1H)-one

HRID 1918817Notes

Reaction equation

HRID 1918817 reaction equation
Br[C:2]1[C:3](=[O:10])[N:4]([CH3:9])[CH:5]=[C:6]([Br:8])[N:7]=1.[NH2:11][C:12]1[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=1.CC(C)([O-])C.[Na+]>C1COCC1>[Br:8][C:6]1[N:7]=[C:2]([NH:11][C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)[C:3](=[O:10])[N:4]([CH3:9])[CH:5]=1

Participants

5

Reactant 3

HCID 100093-AminopyridineHCID 130629693,5-Dibromo-1-methyl-1H-pyrazin-2-oneHCID 23676156Sodium t-butoxide

Product 1

HCID 666133725-Bromo-1-methyl-3-(pyridin-3-ylamino)pyrazin-2(1H)-oneYield 35.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer, reflux condenser and nitrogen inlet was charged with THF (15 mL), 3,5-dibromo-1-methylpyrazin-2(1H)-one (1.00 g, 3.73 mmol), 3-aminopyridine (351 mg, 3.73 mmol) and sodium tert-butoxide (789 mg, 8.21 mmol). After bubbling nitrogen through the resulting solution for 30 min, di-1-bromobis(tri-t-butylphosphino)dipalladium(I) (29 mg, 0.037 mmol) was added, and the reaction mixture was stirred at room temperature for 2.5 h. After this time the reaction was partitioned between ethyl acetate (50 mL) and water (50 mL) and filtered. The aqueous layer was separated and extracted with ethyl acetate (2×25 mL). The organic layers were combined, washed with brine (50 mL) and dried over sodium sulfate. The drying agent was removed by filtration and the filtrate concentrated under reduced pressure. The resulting residue was purified by column chromatography to afford a 35% yield (370 mg) of 111b as a brown solid: mp>250° C.; 1H NMR (500 MHz, DMSO-d6) d 9.75 (s, 1H), 9.08 (d, 1H, J=2.5 Hz), 8.32 (m, 1H), 8.24 (dd, 1H, J=5.0, 1.5 Hz), 7.40 (s, 1H), 7.36 (dd, 1H, J=8.5, 4.5 Hz), 3.45 (s, 3H); MS (APCI+) m/z 281.0 (M+H).

Workup

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer
  2. temperaturereflux condenser and nitrogen inlet
  3. customAfter bubbling nitrogen through the resulting solution for 30 min
  4. customAfter this time the reaction was partitioned between ethyl acetate (50 mL) and water (50 mL)
  5. filtrationfiltered
  6. customThe aqueous layer was separated
  7. extractionextracted with ethyl acetate (2×25 mL)
  8. washwashed with brine (50 mL)
  9. dry with materialdried over sodium sulfate
  10. customThe drying agent was removed by filtration
  11. concentrationthe filtrate concentrated under reduced pressure
  12. customThe resulting residue was purified by column chromatography

Sources & evidence

ORD record
ord-d2628c1076d84efc808cf291cfbfd23d
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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