تفاعل #53442

معادلة التفاعل

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

المردود 24.0%

المذيبات

dioxane

ظروف التفاعل

المعالجة

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

الإجراء التجريبي

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.

المصدر