Dimethylformamide → 2-(1,2,3,4-Tetrahydro-2,8-dimethylpyrido[4,3-b]indol-5-yl)-1-(piperidin-1-yl)ethanone

HRID 1465355Notes

Reaction equation

HRID 1465355 reaction equation
[CH3:1][N:2]1[CH2:19][CH2:18][C:5]2[N:6]([CH2:14][C:15](O)=[O:16])[C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1.C(Cl)(=O)C(Cl)=O.CN(C)C=O.[NH:31]1[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]1>ClCCl.CN(C1C=CN=CC=1)C>[CH3:1][N:2]1[CH2:19][CH2:18][C:5]2[N:6]([CH2:14][C:15]([N:31]3[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]3)=[O:16])[C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 8082PiperidineHCID 65578Oxalyl chlorideHCID 591616282-(1,2,3,4-Tetrahydro-2,8-dimethylpyrido[4,3-b]indol-5-yl)acetic acid

Product 1

HCID 578760482-(1,2,3,4-Tetrahydro-2,8-dimethylpyrido[4,3-b]indol-5-yl)-1-(piperidin-1-yl)ethanoneYield 42.4%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

2-(2,8-dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)acetic acid (1.5 g, 5.8 mmol) was taken in dichloromethane (15 mL) and was cooled to 0° C. using an ice-bath; oxalyl chloride (0.61 mL, 6.9 mmol) was added drop-wise, catalytic amount (2, drop) of dimethyl formamide was added to the reaction mixture. After the addition, reaction mixture was stirred for 1 h at room temperature. Excess oxalyl chloride was distilled away under reduced pressure. To this residue, solution of Piperidine (0.68 mL, 6.9 mmol) in 4 mL DCM and DMAP (0.71 g, 5.8 mmol) was added under nitrogen at room temperature and reaction mass was stirred for 0.5 h at room temperature. The reaction mixture was quenched by ice water and extracted with Dichloromethane and purified by column chromatography to gives 0.8 g of desired compound as free base. The free base was converted into HCl salt by treatment with ethanolic HCl. Sodium hydride (0.8 g, 20 mmol) washed with hexane for removal of oil and dried under vacuum. Then sodium hydride was taken in THF. To this solution 2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (2 g, 10 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 (1.9 g, 12 mmol) in THF was added drop wise in reaction mixture. Then reaction mixture stirred at RT for 2 h. Reaction monitored by TLC. After completion of reaction, reaction mixture quench with ice-water. THE 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 give 1 g of desired compound then it was stirred with ethanolic HCl to give HCl salt of 2-(2,8-dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-1-(piperidin-1-yl)ethanone.

Workup

  1. additionwas added to the reaction mixture
  2. additionAfter the addition, reaction mixture
  3. distillationExcess oxalyl chloride was distilled away under reduced pressure
  4. customreaction mass
  5. stirringwas stirred for 0.5 h at room temperature
  6. customThe reaction mixture was quenched by ice water
  7. extractionextracted with Dichloromethane
  8. custompurified by column chromatography

Sources & evidence

ORD record
ord-3715484e67ad4d57a84b71888cd6de57
Source dataset
uspto-grants-2015_04
Patent number
US08999978B2

Reaction notes

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