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

反応式

HRID 25164 の反応式
[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

参加物

8

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 178418903HCID 178418903、化合物触媒HCID 178505377HCID 178505377、化合物触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-0ee1fb5b7808414d8920f6aced541af2
出典データセット
uspto-grants-2005_02
特許番号
US06858613B2

関連ノート

読み込み中…