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

반응식

HRID 25164 반응식
[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

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 178418903HCID 178418903, 화합물촉매HCID 178505377HCID 178505377, 화합물촉매HCID 312751,4-Dioxane용매

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온도
80 °C

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.

후처리

  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

출처 및 근거

ORD 기록
ord-0ee1fb5b7808414d8920f6aced541af2
출처 데이터셋
uspto-grants-2005_02
특허 번호
US06858613B2

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