Reaktion #53442

Reaktionsgleichung

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

Ausbeute 24.0%

Lösungsmittel

dioxane

Reaktionsbedingungen

Aufarbeitung

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

Vorschrift

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.

Quelle