Sodium hydride → 2-(cyclopropylmethyl)-8-(1-isopropylpiperidin-4-yloxy)-3,4-dihydropyrazino[1,2-a]indol-1(2H)-one

HRID 506671Notes

Reaction equation

HRID 506671 reaction equation
[CH:1]([N:4]1[CH2:9][CH2:8][CH:7]([O:10][C:11]2[CH:19]=[CH:18][C:17]3[N:16]4[CH2:20][CH2:21][NH:22][C:23](=[O:24])[C:15]4=[CH:14][C:13]=3[CH:12]=2)[CH2:6][CH2:5]1)([CH3:3])[CH3:2].[H-].[Na+].Br[CH2:28][CH:29]1[CH2:31][CH2:30]1.[Cl-].[NH4+]>CN(C)C=O>[CH:29]1([CH2:28][N:22]2[CH2:21][CH2:20][N:16]3[C:17]4[CH:18]=[CH:19][C:11]([O:10][CH:7]5[CH2:8][CH2:9][N:4]([CH:1]([CH3:3])[CH3:2])[CH2:5][CH2:6]5)=[CH:12][C:13]=4[CH:14]=[C:15]3[C:23]2=[O:24])[CH2:31][CH2:30]1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 81503BromomethylcyclopropaneHCID 166795188-(1-isopropylpiperidin-4-yloxy)-3,4-dihydropyrazino[1,2-a]indol-1(2H)-one

Product 1

HCID 529412692-(cyclopropylmethyl)-8-(1-isopropylpiperidin-4-yloxy)-3,4-dihydropyrazino[1,2-a]indol-1(2H)-oneYield 38%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To the solution of 0.15 g (0.46 mmol) 8-(1-isopropyl-piperidin-4-yloxy)-3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one (example 1) in 3 mL N,N-dimethylformamide, 24 mg (0.55 mmol, 55% dispersion in mineral oil) sodium hydride was added. After 30 min., 1-(bromomethyl)cyclopropane was added and the mixture was stirred until completion of the reaction as indicated by TLC (2 h). The reaction mixture was poured on 10% aqueous ammonium chloride solution and was extracted three times with ethyl acetate. The organic layers were washed with water and brine, dried over magnesium sulfate, filtered and evaporated. The residue was purified by flash column chromatography on silica gel with dichloromethane:methanol:ammonia (9:1:0.1 v/v) to give the desired compound as a white solid (38%).

Workup

  1. customas indicated by TLC (2 h)
  2. extractionwas extracted three times with ethyl acetate
  3. washThe organic layers were washed with water and brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by flash column chromatography on silica gel with dichloromethane:methanol:ammonia (9:1:0.1 v/v)

Sources & evidence

ORD record
ord-7a4e870fc6f44a56917b7123b245d0ef
Source dataset
uspto-grants-2010_08
Patent number
US07786109B2

Reaction notes

Loading…