Hydrochloric Acid → 2-Methyl-4-(piperidin-1-yl)-N-(3-(trifluoromethyl)benzyl)-1,8-naphthyridine-3-carboxamide

HRID 1961466Notes

Reaction equation

HRID 1961466 reaction equation
[CH3:1][C:2]1[C:11]([C:12]([O:14]CC)=O)=[C:10]([N:17]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)[C:9]2[C:4](=[N:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[OH-].[Na+].Cl.Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.CCN(CC)CC.[F:56][C:57]([F:67])([F:66])[C:58]1[CH:59]=[C:60]([CH:63]=[CH:64][CH:65]=1)[CH2:61][NH2:62]>CCO.O>[CH3:1][C:2]1[C:11]([C:12]([NH:62][CH2:61][C:60]2[CH:63]=[CH:64][CH:65]=[C:58]([C:57]([F:56])([F:66])[F:67])[CH:59]=2)=[O:14])=[C:10]([N:17]2[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22]2)[C:9]2[C:4](=[N:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1

Participants

10

Reactant 7

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 759623-(Trifluoromethyl)benzylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 66634229HCID 66634229, compound

Product 1

HCID 469085792-Methyl-4-(piperidin-1-yl)-N-(3-(trifluoromethyl)benzyl)-1,8-naphthyridine-3-carboxamideYield 12%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

Ethyl 2-methyl-4-(piperidin-1-yl)-1,8-naphthyridine-3-carboxylate (120.0 mg, 0.4 mmol) was dissolved in EtOH. NaOH (4.0 ml of a 1.0 M aq. solution) was added and the mixture refluxed for 3.0 days. The mixture was cooled, acidified with aq. HCl (1.0 M) and concentrated to dryness. The residue was suspended in anhydrous THF, N-(3-dimethylaminopropyl)-N′-ethyl-carbodiimide hydrochloride (84.34 mg, 0.44 mmol), 1-hydroxybenzotriazole hydrate (30.74 mg, 0.2 mmol.) and Et3N (54.8 μl, 0.4 mmol) were added. The mixture was stirred at room temperature for 30 min. 3-(trifluoromethyl)benzyl amine (57.33 μl, 0.4 mmol) was added to the mixture and stirring continued for 18 h. H2O was added to the mixture and the product extracted with EtOAc, dried over MgSO4 and concentrated. Purification was done by flash chromatography (CH2Cl2/MeOH 98:2→96:4) giving 20.0 mg (12%) of the title compound.

Workup

  1. temperaturethe mixture refluxed for 3.0 days
  2. temperatureThe mixture was cooled
  3. concentrationconcentrated to dryness
  4. stirringstirring
  5. waitcontinued for 18 h
  6. extractionthe product extracted with EtOAc
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. customPurification

Sources & evidence

ORD record
ord-92e0c5ada0b84da7be64a8e86960473f
Source dataset
uspto-grants-2013_04
Patent number
US08415333B2

Reaction notes

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