methyl 4-{(3S)-3-[(4-{[(3,4-dichlorophenyl)amino]carbonyl}piperazin-1-yl)methyl]piperidin-1-yl}-4-oxobutanoate → methyl 4-{(3R)-3-[(4-{[(3,4-dichlorophenyl)amino]carbonyl}piperazin-1-yl)methyl]piperidin-1-yl}butanoate

HRID 603232ノート

反応式

HRID 603232 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]([N:12]2[CH2:17][CH2:16][N:15]([CH2:18][C@@H:19]3[CH2:24][CH2:23][CH2:22][N:21]([C:25](=O)[CH2:26][CH2:27][C:28]([O:30][CH3:31])=[O:29])[CH2:20]3)[CH2:14][CH2:13]2)=[O:11])[CH:5]=[CH:6][C:7]=1[Cl:8]>O1CCCC1>[NH3:9].[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]([N:12]2[CH2:17][CH2:16][N:15]([CH2:18][C@@H:19]3[CH2:24][CH2:23][CH2:22][N:21]([CH2:25][CH2:26][CH2:27][C:28]([O:30][CH3:31])=[O:29])[CH2:20]3)[CH2:14][CH2:13]2)=[O:11])[CH:5]=[CH:6][C:7]=1[Cl:8]

参加物

4

反応物 1

HCID 57656799methyl 4-{(3S)-3-[(4-{[(3,4-dichlorophenyl)amino]carbonyl}piperazin-1-yl)methyl]piperidin-1-yl}-4-oxobutanoate

生成物 2

HCID 222AmmoniaHCID 57656696methyl 4-{(3R)-3-[(4-{[(3,4-dichlorophenyl)amino]carbonyl}piperazin-1-yl)methyl]piperidin-1-yl}butanoate収率 68.6%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

To a solution of methyl 4-{(3S)-3-[(4-{[(3,4-dichlorophenyl)amino]carbonyl}piperazin-1-yl)methyl]piperidin-1-yl}-4-oxobutanoate (240 mg) in tetrahydrofuran (5 mL) at room temperature under argon was added a 1M solution of BH3 in THF (1 mL). The solution was heated to reflux temperature for 1 hour and then cooled to ambient temperature. The reaction was quenched with methanol and then concentrated at reduced pressure. To the residue was added saturated HCl in methanol (10 mL) and the mixture was heated to reflux temperature for 1 hour and then cooled to ambient temperature. The mixture was stirred at ambient temperature overnight and then concentrated at reduced pressure. The residue was purified using reverse phase HPLC eluting with a mixture of 5-95% acetonitrile in water and then SCX-2 column eluting with methanol then 7M NH3 in methanol to give methyl 4-{(3R)-3-[(4-{[(3,4-dichlorophenyl)amino]carbonyl}piperazin-1-yl)methyl]piperidin-1-yl}butanoate (80 mg, 34%).

後処理

  1. temperatureThe solution was heated
  2. temperatureto reflux temperature for 1 hour
  3. customThe reaction was quenched with methanol
  4. concentrationconcentrated at reduced pressure
  5. additionTo the residue was added saturated HCl in methanol (10 mL)
  6. temperaturethe mixture was heated
  7. temperatureto reflux temperature for 1 hour
  8. temperaturecooled to ambient temperature
  9. concentrationconcentrated at reduced pressure
  10. customThe residue was purified
  11. washeluting with a mixture of 5-95% acetonitrile in water
  12. washSCX-2 column eluting with methanol

出典と根拠

ORDレコード
ord-99951566c1f947fe80661d04e6b1e6ce
出典データセット
uspto-grants-2011_03
特許番号
US07906645B2

反応ノート

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