Sulfuric Acid → HCID 118078834, compound

HRID 1485679Notes

Reaction equation

HRID 1485679 reaction equation
[Br:1][C:2]1[CH:11]=[N:10][C:9]2[N:8]([C:12](=[O:14])[CH3:13])[C@@H:7]([CH3:15])[CH2:6][N:5](S(C3C=CC(C)=CC=3)(=O)=O)[C:4]=2[CH:3]=1.S(=O)(=O)(O)O>>[Br:1][C:2]1[CH:11]=[N:10][C:9]2[N:8]([C:12](=[O:14])[CH3:13])[C@@H:7]([CH3:15])[CH2:6][NH:5][C:4]=2[CH:3]=1

Participants

3

Reactant 2

HCID 1118Sulfuric AcidHCID 118080368HCID 118080368, compound

Product 1

HCID 118078834HCID 118078834, compoundYield 50.2%

Procedure

A 50-mL round bottomed flask was charged with (S)-1-(7-bromo-3-methyl-1-tosyl-2,3-dihydropyrido[3,2-b]pyrazin-4(1H)-yl)ethanone (1.2 g, 2.83 mmol) and sulfuric acid (5.79 mL, 109 mmol). A slight exotherm was observed. The mixture was stirred until all the substrate dissolved (ca. 20-30 min). After a total of 30-45 min, the pale yellow solution was carefully pipetted onto crushed ice (50 g). The flask was rinsed with a small portion of water (ca. 2 mL), which was also added to the crushed ice. The crushed ice/aqueous solution mixture was then stirred as 10 N aqueous sodium hydroxide solution was slowly added while maintaining the internal temperature below 9° C. (with the aid of an external crushed ice/water bath). The pH was adjusted to 11-12 (a total of ca. 22 mL 10 N aqueous sodium hydroxide solution was added). After the addition was complete, the mixture was poured into a separatory funnel and extracted with dichloromethane. The dichloromethane layer was washed with water (2×30 mL) and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (eluting with 4:1 dichloromethane-ethyl acetate) to afford (5)-1-(7-bromo-3-methyl-2,3-dihydropyrido[3,2-b]pyrazin-4(1H)-yl)ethanone (384 mg, 50%) as a colorless foam. MS (ESI, pos. ion) m/z 270, 272 [M+1]+.

Workup

  1. dissolutiondissolved (ca. 20-30 min)
  2. customAfter a total of 30-45 min
  3. washThe flask was rinsed with a small portion of water (ca. 2 mL), which
  4. additionwas also added to the crushed ice
  5. stirringThe crushed ice/aqueous solution mixture was then stirred as 10 N aqueous sodium hydroxide solution
  6. additionwas slowly added
  7. temperaturewhile maintaining the internal temperature below 9° C. (with the aid of
  8. customan external crushed ice/water bath)
  9. additionwas added)
  10. additionAfter the addition
  11. additionthe mixture was poured into a separatory funnel
  12. extractionextracted with dichloromethane
  13. washThe dichloromethane layer was washed with water (2×30 mL)
  14. concentrationconcentrated under reduced pressure
  15. customThe crude product was purified by column chromatography on silica gel (eluting with 4:1 dichloromethane-ethyl acetate)

Sources & evidence

ORD record
ord-41270904bd32446cb5d9de9e1d7a0977
Source dataset
uspto-grants-2016_08
Patent number
US09422281B2

Reaction notes

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