2-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde synthesis

9synthesis methods

Product Name:2-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde
CAS Number:1185428-34-5
Molecular formula:C13H18BrN3O2Si
Molecular Weight:356.29

2-BroMo-5H-pyrrolo[2,3-b]pyrazine-7-carboxaldehyde

1185428-32-3
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76513-69-4 Synthesis

76513-69-4
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2-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde

1185428-34-5
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Yield:1185428-34-5 53%

Reaction Conditions:

Stage #1: 2-bromo-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehydewith sodium hydride in N,N-dimethyl-d₆-formamide;mineral oil at 0 - 20; for 0.5 h;
Stage #2: (2-trimethylethylsilylethoxy)methyl chloride in N,N-dimethyl-formamide;mineral oil at 0 - 20; for 1 h;

Steps:

1.A.3 2-Bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolor2,3-blpyrazine-7-carbaldehyde

A stock solution of Jones reagent (2.67 M) was prepared by carefully adding concentrated H₂S0₄ (2.3 mL) to Cr0₃ (2.67 g) then diluting to 10 mL with H₂0. 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 H₂0 and extracted with EtOAc (3x). The combined organics were washed with H₂0 (3x) and brine then dried over MgS0₄ and concentrated. The residue was purified by Si0₂ 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 (CDC1₃, 300 MHz): δ (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).

References:

WO2014/29732,2014,A1 Location in patent:Page/Page column 38; 39