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 710786Notes

Reaction equation

HRID 710786 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-78659eed70be4684afb6c613d8c59ef8
Source dataset
uspto-grants-2015_11
Patent number
US09181240B2

Reaction notes

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