반응 #53442

반응 방정식

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

수율 24.0%

용매

dioxane

반응 조건

후처리

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

실험 절차

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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