2-Methylpiperidine → 2-(8-Chloro-1,2,3,4-tetrahydro-2-methylpyrido[4,3-b]indol-5-yl)-1-(2-methylpiperidin-1-yl)ethanone

HRID 2195910Notes

Reaction equation

HRID 2195910 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]([CH2:11][C:12]([OH:14])=O)[C:6]3[CH2:15][CH2:16][N:17]([CH3:19])[CH2:18][C:5]=3[C:4]=2[CH:3]=1.C(Cl)(=O)C(Cl)=O.[CH3:26][CH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][NH:28]1>ClCCl.CN(C1C=CN=CC=1)C>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]([CH2:11][C:12]([N:28]3[CH2:29][CH2:30][CH2:31][CH2:32][CH:27]3[CH3:26])=[O:14])[C:6]3[CH2:15][CH2:16][N:17]([CH3:19])[CH2:18][C:5]=3[C:4]=2[CH:3]=1

Participants

6

Reactant 3

HCID 79742-MethylpiperidineHCID 65578Oxalyl chlorideHCID 59161636HCID 59161636, compound

Product 1

HCID 578758862-(8-Chloro-1,2,3,4-tetrahydro-2-methylpyrido[4,3-b]indol-5-yl)-1-(2-methylpiperidin-1-yl)ethanoneYield 19.4%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 2-(8-chloro-1,2,3,4-tetrahydro-2-methylpyrido[4,3-b]indol-5-yl)acetic acid (125 mg, 0.45 mmol) and oxalyl chloride (2 ml) in dichloromethane (6.0 ml) was stirred at 25 deg C. for 3 h. After completion of the reaction (monitored by TLC), the reaction mixture was concentrated to dryness. To the resulting crude dichloromethane (6.0 ml) and DMAP (64 mg, 0.52 mmol) was added followed by addition of 2-methylpiperidine (43 mg, 0.43 mmol). The resulting mixture was stirred at 25 deg C. for 14 h. After completion of the reaction (monitored by LCMS), solvent was removed in vacuo and purified by reverse-phase chromatography (C-18, 500 mm×50 mm, Mobile Phase A=0.05% TFA in water, B=0.05% TFA in acetonitrile, Gradient: 10% B to 80% B in 30 min, injection vol. 5 mL) to obtain 30 mg of 2-(8-chloro-1,2,3,4-tetrahydro-2-methylpyrido[4,3-b]indol-5-yl)-1-(2-methylpiperidin-1-yl)ethanone as trifluoroacetic acid salt.

Workup

  1. customAfter completion of the reaction (monitored by TLC)
  2. concentrationthe reaction mixture was concentrated to dryness
  3. stirringThe resulting mixture was stirred at 25 deg C
  4. waitfor 14 h
  5. customAfter completion of the reaction (monitored by LCMS), solvent
  6. customwas removed in vacuo
  7. custompurified by reverse-phase chromatography (C-18, 500 mm×50 mm, Mobile Phase A=0.05% TFA in water, B=0.05% TFA in acetonitrile, Gradient: 10% B to 80% B in 30 min, injection vol. 5 mL)

Sources & evidence

ORD record
ord-87fd098bbfa34041808cd2436163d6cd
Source dataset
uspto-grants-2012_12
Patent number
US08338408B2

Reaction notes

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