Sodium hydride → 2-(8-bromo-2-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-1-(piperidin-1-yl)ethanone

HRID 2196036Notes

Reaction equation

HRID 2196036 reaction equation
[H-].[Na+].[Br:3][C:4]1[CH:12]=[CH:11][C:10]2[NH:9][C:8]3[CH2:13][CH2:14][N:15]([CH3:17])[CH2:16][C:7]=3[C:6]=2[CH:5]=1.Cl[CH2:19][C:20]([N:22]1[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1)=[O:21]>CCCCCC.C1COCC1>[Br:3][C:4]1[CH:12]=[CH:11][C:10]2[N:9]([CH2:19][C:20]([N:22]3[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]3)=[O:21])[C:8]3[CH2:13][CH2:14][N:15]([CH3:17])[CH2:16][C:7]=3[C:6]=2[CH:5]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 1998168-Bromo-2,3,4,5-tetrahydro-2-methyl-1H-pyrido(4,3-b)indoleHCID 2223122-Chloro-1-piperidine-1-yl-ethanone

Product 1

HCID 447719132-(8-bromo-2-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-1-(piperidin-1-yl)ethanoneYield 51.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

Sodium hydride (0.6 g, 15 mmol) washed with hexane for removal of oil and dried under vacuum. Then sodium hydride was taken in THF. To this solution 8-bromo-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (2 g, 7.5 mmol) in THF was added drop wise at 0° C. Then reaction mixture stirred for 0.5 h. The solution of 2-chloro-1-(piperidin-1-yl)ethanone (1.8 g, 11.3 mmol) in THF was added drop wise in reaction mixture. Then reaction mixture stirred at rt for 2 h. Reaction was monitored by TLC. After completion of the reaction, reaction mixture quench with ice-water. THF was evaporated and aqueous layer was extracted with ethyl acetate. Organic layer was dried over anhydrous sodium sulphate. The crude compound was washed with hexane and diethyl ether for removal of color impurities then recrystallized by using methanol to gives 1.5 g of desired compound then out of that 0.8 g compound was stirred in ethanolic HCl to give HCl salt of 2-(8-bromo-2-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-1-(piperidin-1-yl)ethanone.

Workup

  1. customdried under vacuum
  2. customThen reaction mixture
  3. customwise in reaction mixture
  4. customThen reaction mixture
  5. stirringstirred at rt for 2 h
  6. customReaction
  7. customAfter completion of the reaction, reaction mixture
  8. customquench with ice-water
  9. customTHF was evaporated
  10. extractionaqueous layer was extracted with ethyl acetate
  11. dry with materialOrganic layer was dried over anhydrous sodium sulphate
  12. washThe crude compound was washed with hexane and diethyl ether for removal of color impurities
  13. customthen recrystallized

Sources & evidence

ORD record
ord-5b8a387205ea49db8dc28368dd5417a7
Source dataset
uspto-grants-2012_12
Patent number
US08338408B2

Reaction notes

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