Реакция #53442

Уравнение реакции

d-tartaric acid

N-[(3R)— 1-azabicyclo[2.2.2]oct-3-yl]-6-bromopyrrolo[1,2-a]pyrazine-3-carboxamide

triethylamine

propargyl alcohol

→

N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-6-(3-hydroxyprop-1-ynyl)pyrrolo [1,2-a]pyrazine-3-carboxamide Tartrate

Выход 24.0%

Растворители

dioxane

Условия реакции

Обработка

1. 1
   ДругоеThe reaction vessel is purged with argon
2. 2
   Фильтрацияis filtered through a plug of celite,
3. 3
   Концентрированиеconcentrated to dryness
4. 4
   workup.DISSOLUTIONthe residue dissolved in CHCl3 (150 mL) that
5. 5
   Промывкаis washed with a solution
6. 6
   workup.ADDITIONcontaining 1:1 NH4OH/brine (5×35 mL)
7. 7
   ДругоеThe residue is purified
8. 8
   Другоеto give a pale orange colored oil that
9. 9
   Другоеcrystallized from EtOH/Et2O
10. 10
    Другоеto give a tan solid

Методика

To an argon sparged solution of N-[(3R)— 1-azabicyclo[2.2.2]oct-3-yl]-6-bromopyrrolo[1,2-a]pyrazine-3-carboxamide (0.230 g, 0.92 mmol), triethylamine (3.2 mL, 23.0 mmol) in dioxane (5 mL) is added copper (I) iodine (0.054 g, 0.28 mmol), propargyl alcohol (0.22 mL, 3.68 mmol), and dichlorobis(triphenylphosphino)-palladium (II) (0.063 g, 0.09 mmol). The reaction vessel is purged with argon, and stirred at 80° C. for 20 h at which point it is filtered through a plug of celite, concentrated to dryness, and the residue dissolved in CHCl3 (150 mL) that is washed with a solution containing 1:1 NH4OH/brine (5×35 mL). The residue is purified using silica gel chromatography (5% MeOH/CH2Cl2 gradient up to 10% MeOH/CH2Cl2) to give a pale orange colored oil that is salted with d-tartaric acid, and crystallized from EtOH/Et2O to give a tan solid. Yield 24%. HRMS (FAB) calcd for C18H20N4O2+H 325.1664, found 325.1664.

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