Water → (S)-1-(8-chloro-1-(1-(methylsulfonyl)piperidin-4-yloxy)isoquinolin-3-yl)ethanamine

HRID 1396630ノート

反応式

HRID 1396630 の反応式
[CH3:1][S:2]([N:5]1[CH2:10][CH2:9][CH:8]([OH:11])[CH2:7][CH2:6]1)(=[O:4])=[O:3].[H-].[Na+].Cl[C:15]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][C:23]=2[Cl:25])[CH:18]=[C:17]([C@@H:26]([NH:28]C(=O)OCC2C3C=CC=CC=3C3C2=CC=CC=3)[CH3:27])[N:16]=1.O>C1COCC1>[Cl:25][C:23]1[CH:22]=[CH:21][CH:20]=[C:19]2[C:24]=1[C:15]([O:11][CH:8]1[CH2:7][CH2:6][N:5]([S:2]([CH3:1])(=[O:4])=[O:3])[CH2:10][CH2:9]1)=[N:16][C:17]([C@@H:26]([NH2:28])[CH3:27])=[CH:18]2

参加物

6

反応物 4

HCID 962WaterHCID 24758Sodium hydrideHCID 222729811-Methanesulfonylpiperidin-4-olHCID 86665027HCID 86665027、化合物

生成物 1

HCID 68751363(S)-1-(8-chloro-1-(1-(methylsulfonyl)piperidin-4-yloxy)isoquinolin-3-yl)ethanamine

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a mixture of 1-(methylsulfonyl)piperidin-4-ol (618 mg, 3.45 mmol, 1.6 eq) in THF (5 mL) at 0° C., NaH (60% in mineral oil, 173 mg, 4.32 mmol, 2.0 eq) was added and the resulting mixture was stirred for 10 min. To this mixture, (S)-(9H-fluoren-9-yl)methyl 1-(1,8-dichloroisoquinolin-3-yl)ethylcarbamate 69 (1.0 g, 2.16 mmol, 1.0 eq) was added and the resulting mixture was stirred at reflux for 2 h. The mixture was cooled to RT and poured into water (20 mL). The mixture was extracted with ethyl acetate (3×20 mL). The combined organic layer was washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by flash column chromatography on silica gel (3% MeOH-DCM) to afford the product (S)-1-(8-chloro-1-(1-(methylsulfonyl)piperidin-4-yloxy)isoquinolin-3-yl)ethanamine (175).

後処理

  1. stirringthe resulting mixture was stirred
  2. temperatureat reflux for 2 h
  3. extractionThe mixture was extracted with ethyl acetate (3×20 mL)
  4. washThe combined organic layer was washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuo
  8. customthe residue was purified by flash column chromatography on silica gel (3% MeOH-DCM)

出典と根拠

ORDレコード
ord-73a103f40bff4f8dae291b6951670719
出典データセット
uspto-grants-2014_12
特許番号
US08901133B2

反応ノート

読み込み中…