Sulfuric Acid → 2-Bromo-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde

HRID 522941Notes

Reaction equation

HRID 522941 reaction equation
[OH:1][S:2]([OH:5])(=[O:4])=[O:3].[Br:6][C:7]1[N:8]=[C:9]2[C:15]([CH2:16][OH:17])=[CH:14][NH:13][C:10]2=[N:11][CH:12]=1.[CH3:18][C:19]([CH3:21])=[O:20].OS(O)(=O)=O.[O:27]=[Cr:28](=[O:30])=[O:29]>O.CC(C)=O>[CH3:18][C:19]([CH3:21])=[O:20].[OH:4][S:2]([OH:5])(=[O:3])=[O:1].[O:27]=[Cr:28](=[O:30])=[O:29].[Br:6][C:7]1[N:8]=[C:9]2[C:15]([CH:16]=[O:17])=[CH:14][NH:13][C:10]2=[N:11][CH:12]=1

Participants

7

Reactant 3

HCID 1118Sulfuric AcidHCID 57516586HCID 57516586, compoundHCID 131709961Jones' reagent

Product 2

HCID 575165872-Bromo-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehydeHCID 131709961Jones' reagent

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent

Procedure

A stock solution of Jones reagent (2.67 M) was prepared by carefully adding concentrated H2SO4 (2.3 mL) to CrO3 (2.67 g) then diluting to 10 mL with H2O. To a partial suspension of (2-bromo-5H-pyrrolo[2,3-b]pyrazin-7-yl)-methanol (4.6 g, 20.1 mmol) in acetone (300 mL) was slowly added Jones reagent (9 mL, 24.0 mmol). During the addition the starting material gradually dissolved and a thick green precipitate was formed. The reaction mixture was stirred for 15 min then quenched with i-PrOH (2 mL) and filtered over Celite, rinsing with acetone. The filtrate was concentrated to provide 4.76 g of 2-bromo-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde as a yellow-orange solid that was used without further purification. To a solution of this solid in DMF (50 mL) at 0° C. was added NaH (60% in mineral oil, 1.2 g, 30.1 mmol). The reaction mixture was stirred at room temperature for 30 min then cooled back to 0° C. and 2-(trimethylsilyl)ethoxymethyl chloride (4.3 mL, 24.1 mmol) was slowly added. The reaction mixture was warmed to room temperature and stirred for 1 h then quenched with H2O and extracted with EtOAc (3×). The combined organics were washed with H2O (3×) and brine then dried over MgSO4 and concentrated. The residue was purified by SiO2 chromatography (20% to 30% EtOAc/hexanes) to isolate 3.82 g (53%) of 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde as a yellow solid. 1H NMR (CDCl3, 300 MHz): 6 (ppm) 10.37 (s, 1H), 8.50 (s, 1H), 8.33 (s, 1H), 5.73 (s, 2H), 3.53-3.70 (m, 2H), 0.90-1.05 (m, 2H), 0.00 (s, 9H).

Workup

  1. additionDuring the addition the starting material
  2. dissolutiongradually dissolved
  3. customa thick green precipitate was formed
  4. customthen quenched with i-PrOH (2 mL)
  5. filtrationfiltered over Celite
  6. washrinsing with acetone
  7. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-4d1f60d8f8684c1987f102a3be35581c
Source dataset
uspto-grants-2016_05
Patent number
US09334278B2

Reaction notes

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