Sodium Hydroxide → (R)-(+)-N-(1-azabicyclo[2.2.2]oct-3-yl)-7-methylpyrazolo[1,5-a]pyridine-3-carboxamide

HRID 1589836ノート

反応式

HRID 1589836 の反応式
[CH3:1][C:2]1[N:7]2[N:8]=[CH:9][C:10]([C:11]([OH:13])=O)=[C:6]2[CH:5]=[CH:4][CH:3]=1.[N:14]12[CH2:21][CH2:20][CH:17]([CH2:18][CH2:19]1)[C@@H:16]([NH2:22])[CH2:15]2.[OH-].[Na+]>S(Cl)(Cl)=O.C(Cl)Cl.C(OCC)(=O)C>[N:14]12[CH2:21][CH2:20][CH:17]([CH2:18][CH2:19]1)[C@@H:16]([NH:22][C:11]([C:10]1[CH:9]=[N:8][N:7]3[C:2]([CH3:1])=[CH:3][CH:4]=[CH:5][C:6]=13)=[O:13])[CH2:15]2

参加物

7

反応物 3

HCID 14798Sodium HydroxideHCID 719215(3R)-1-Azabicyclo(2.2.2)octan-3-amineHCID 197709687-Methylpyrazolo[1,5-a]pyridine-3-carboxylic acid

生成物 1

HCID 53974511(R)-(+)-N-(1-azabicyclo[2.2.2]oct-3-yl)-7-methylpyrazolo[1,5-a]pyridine-3-carboxamide収率 77.2%

試薬・触媒・溶媒 3

HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒HCID 24386Thionyl Chloride溶媒

実験手順

A solution of 166 mg (0.945 mmol) of 7-methyl-3-pyrazolo[1,5-a]pyridinecarboxylic acid in 3 ml of thionyl chloride was heated under reflux for 30 minutes. Thionyl chloride was distilled off under reduced pressure and the residue was dissolved in 5 ml of methylene chloride. The resultant solution was added dropwise under ice cooling to a solution of 200 mg (1 mmol) of (R)-(+)-1-azabicyclo[2.2.2]octan-3-amine, which had been prepared in accordance with the procedure disclosed in Japanese Patent Application Laid-Open No. 196583/1988, in 5 ml of methylene chloride. The resultant mixture was stirred for 30 minutes under ice cooling and for additional 40 minutes at room temperature. 2N aq. NaOH solution was added to the reaction mixture and, after the mixture so obtained was stirred for 10 minutes, the organic layer was collected. Further, the water layer was extracted with methylene chloride and the extract was dried over anhydrous potassium carbonate. Methylene chloride was distilled off under reduced pressure, and the residue was purified by chromatography on a silica gel column (chloroform:methanol=10:1, 5:1). An oily substance thus obtained was dissolved in ethyl acetate. The solvent was distilled off under reduced pressure, and crystals thus obtained were washed with ether, whereby 207 mg (0.73 mmol) of the title compound were obtained as white crystals (yield: 77.0%).

後処理

  1. temperatureunder reflux for 30 minutes
  2. distillationThionyl chloride was distilled off under reduced pressure
  3. dissolutionthe residue was dissolved in 5 ml of methylene chloride
  4. customhad been prepared in accordance with the procedure
  5. customafter the mixture so obtained
  6. customthe organic layer was collected
  7. extractionFurther, the water layer was extracted with methylene chloride
  8. dry with materialthe extract was dried over anhydrous potassium carbonate
  9. distillationMethylene chloride was distilled off under reduced pressure
  10. customthe residue was purified by chromatography on a silica gel column (chloroform:methanol=10:1, 5:1)
  11. customAn oily substance thus obtained
  12. distillationThe solvent was distilled off under reduced pressure, and crystals
  13. customthus obtained
  14. washwere washed with ether

出典と根拠

ORDレコード
ord-f7e5755b7c05451f927ba8a9fe2c5f3b
出典データセット
uspto-grants-1993_04
特許番号
US05200415

反応ノート

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