Dimethylformamide → N-[(1-Butylpiperidin-4-yl)methyl]-5-chloro-1-isopropyl-2-oxo-1,2-dihydroquinoline-3-carboxamide hydrochloride

HRID 2425761Notes

Reaction equation

HRID 2425761 reaction equation
[Cl:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[C:5]([C:16]([OH:18])=O)[C:6](=[O:15])[N:7]2[CH:12]([CH3:14])[CH3:13].C(Cl)(=O)C(Cl)=O.CN(C)C=O.[CH2:30]([N:34]1[CH2:39][CH2:38][CH:37]([CH2:40][NH2:41])[CH2:36][CH2:35]1)[CH2:31][CH2:32][CH3:33]>ClCCl.Cl>[ClH:1].[CH2:30]([N:34]1[CH2:39][CH2:38][CH:37]([CH2:40][NH:41][C:16]([C:5]2[C:6](=[O:15])[N:7]([CH:12]([CH3:13])[CH3:14])[C:8]3[C:3]([CH:4]=2)=[C:2]([Cl:1])[CH:11]=[CH:10][CH:9]=3)=[O:18])[CH2:36][CH2:35]1)[CH2:31][CH2:32][CH3:33]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 104421334-Aminomethyl-1-N-butylpiperidineHCID 598224655-Chloro-1-isopropyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid

Product 1

HCID 67246281N-[(1-Butylpiperidin-4-yl)methyl]-5-chloro-1-isopropyl-2-oxo-1,2-dihydroquinoline-3-carboxamide hydrochlorideYield 117.1%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 5-chloro-1-isopropyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid (100 mg, 0.376 mmol, step 4) in dichloromethane (1 mL) was added oxalyl chloride (0.10 mL, 1.13 mmol) and a drop of N,N-dimethylformamide at 0° C. The mixture was stirred at room temperature for 1.5 h. The solvent and excess amount of oxalyl chloride was removed in vacuo. The residue was dissolved in dichloromethane (1 mL) and [(1-butylpiperidin-4-yl)methyl]amine (128 mg, 0.753 mmol) in dichloromethane (1 mL) was added at 0° C. and the mixture was stirred at room temperature for 1 h. Then, the mixture was quenched with water (10 mL) and the aqueous layer was extracted with dichloromethane (20 mL×2). The organic layer was dried over sodium sulfate and concentrated in vacuo gave a colorless oil. The resultant oil was dissolved in 10% methanolic hydrogen chloride (5 mL) and stirred for 16 h. The formed precipitate was filtrated and washed with methanol to give 100 mg (59%) of the title compound as a white solid.

Workup

  1. customat 0° C
  2. customThe solvent and excess amount of oxalyl chloride was removed in vacuo
  3. dissolutionThe residue was dissolved in dichloromethane (1 mL)
  4. stirringthe mixture was stirred at room temperature for 1 h
  5. customThen, the mixture was quenched with water (10 mL)
  6. extractionthe aqueous layer was extracted with dichloromethane (20 mL×2)
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customgave a colorless oil
  10. stirringstirred for 16 h
  11. filtrationThe formed precipitate was filtrated
  12. washwashed with methanol

Sources & evidence

ORD record
ord-3fa8a6ef4b57483093f86f05a043821f
Source dataset
uspto-grants-2011_06
Patent number
US07964727B2

Reaction notes

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