N,N-二甲基甲酰胺 → (S)-3-[(1-azabicyclo[2.2.2]oct-3-yl)aminocarbonyl]-1,2-dimethylindole

HRID 2082319

反应方程式

HRID 2082319 反应方程式
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([C:11]([OH:13])=O)=[C:3]1[CH3:14].C(Cl)(=O)C(Cl)=O.CN(C)C=O.[NH2:26][C@H:27]1[CH:32]2[CH2:33][CH2:34][N:29]([CH2:30][CH2:31]2)[CH2:28]1>ClCCl>[N:29]12[CH2:34][CH2:33][CH:32]([CH2:31][CH2:30]1)[C@H:27]([NH:26][C:11]([C:4]1[C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[N:2]([CH3:1])[C:3]=1[CH3:14])=[O:13])[CH2:28]2

参与物

6

反应物 4

HCID 6228N,N-二甲基甲酰胺HCID 65578草酰氯HCID 719216(S)-quinuclidin-3-amineHCID 27610321,2-二甲基吲哚-3-甲酸

产物 1

HCID 53942173(S)-3-[(1-azabicyclo[2.2.2]oct-3-yl)aminocarbonyl]-1,2-dimethylindole收率 46%

试剂、催化剂与溶剂 1

HCID 6344二氯甲烷溶剂2 次

实验过程

1,2-dimethylindole-3-carboxylic acid (1.05 g, 5.5 mmol) was dissolved with oxalyl chloride (0.55 ml, 6 mmol) and dimethylformamide (0.1 ml) in dichloromethane (30 ml) and stirred at room temperature for one hour. The mixture was then concentrated under reduced pressure, and the residue was dissolved in dichloromethane (20 ml). The resulting mixture was added dropwise at 0° C. to a solution of (S)-3-amino-1-azabicyclo[2.2.2]octane (0.7 g, 5.5 mmol) in dichloromethane (10 ml). The solution was stirred at room temperature for 30 minutes, after which the solvent was removed under vacuum. The residue was dissolved in water and washed with ethyl acetate. The aqueous layer was made basic with 10N aqueous sodium hydroxide, filtered and extracted with ethyl acetate. The organic layer was dried with anhydrous potassium carbonate, filtered, and then evaporated. Recrystallization from ethyl acetate afforded 0.7 g (46% yield) (S)-3-[(1-azabicyclo[2.2.2]oct-3-yl)aminocarbonyl]-1,2-dimethylindole, m.p. 176°-177° C.; [α]D25 -51.90 (c 0.92, CHCl3). Anal. for C18H23N3O: Calcd: C, 72.70; H, 7.79; N, 14.13. Found: C, 72.75; H, 7.89; N, 14.15.

后处理

  1. concentrationThe mixture was then concentrated under reduced pressure
  2. dissolutionthe residue was dissolved in dichloromethane (20 ml)
  3. stirringThe solution was stirred at room temperature for 30 minutes
  4. customafter which the solvent was removed under vacuum
  5. dissolutionThe residue was dissolved in water
  6. washwashed with ethyl acetate
  7. filtrationfiltered
  8. extractionextracted with ethyl acetate
  9. dry with materialThe organic layer was dried with anhydrous potassium carbonate
  10. filtrationfiltered
  11. customevaporated
  12. customRecrystallization from ethyl acetate

来源与证据

ORD记录
ord-39b293351cc0478ab78c887d84b8e774
来源数据集
uspto-grants-1993_02
专利号
US05189041

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