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

HRID 25164

Reaktionsgleichung

Reaktionsgleichung von HRID 25164
[N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[C@@H:3]([NH:9][C:10]([C:12]1[N:13]=[CH:14][C:15]3[N:16]([C:18](Br)=[CH:19][CH:20]=3)[CH:17]=1)=[O:11])[CH2:2]2.C(N(CC)CC)C.[CH2:29]([OH:32])[C:30]#[CH:31].[C:33]([OH:42])(=[O:41])[C@H:34]([C@@H:36]([C:38]([OH:40])=[O:39])[OH:37])[OH:35]>O1CCOCC1.[I+].[Cu+].Cl[Pd-2](Cl)(P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:38]([CH:36]([CH:34]([C:33]([OH:42])=[O:41])[OH:35])[OH:37])([OH:40])=[O:39].[N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[C@@H:3]([NH:9][C:10]([C:12]1[N:13]=[CH:14][C:15]3[N:16]([C:18]([C:31]#[C:30][CH2:29][OH:32])=[CH:19][CH:20]=3)[CH:17]=1)=[O:11])[CH2:2]2

Komponenten

8

Edukt 4

HCID 7859Propargyl alcoholHCID 8471TriethylamineHCID 439655D-Tartaric acidHCID 10247203N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-6-bromopyrrolo[1,2-a]pyrazine-3-carboxamide

Produkt 1

HCID 69772344N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-6-(3-hydroxyprop-1-ynyl)pyrrolo[1,2-a]pyrazine-3-carboxamide tartrateAusbeute 24 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418903HCID 178418903, VerbindungKatalysatorHCID 178505377HCID 178505377, VerbindungKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

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.

Aufarbeitung

  1. customThe reaction vessel is purged with argon
  2. filtrationis filtered through a plug of celite,
  3. concentrationconcentrated to dryness
  4. dissolutionthe residue dissolved in CHCl3 (150 mL) that
  5. washis washed with a solution
  6. additioncontaining 1:1 NH4OH/brine (5×35 mL)
  7. customThe residue is purified
  8. customto give a pale orange colored oil that
  9. customcrystallized from EtOH/Et2O
  10. customto give a tan solid

Quellen und Nachweise

ORD-Eintrag
ord-0ee1fb5b7808414d8920f6aced541af2
Quelldatensatz
uspto-grants-2005_02
Patentnummer
US06858613B2

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