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

HRID 1051797Notes

Reaction equation

HRID 1051797 reaction equation
[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

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 222729811-Methanesulfonylpiperidin-4-olHCID 86665027HCID 86665027, compound

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-88b1a8a20aa0468f8d5b736c20c0c2c2
Source dataset
uspto-grants-2016_07
Patent number
US09388183B2

Reaction notes

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