Triethylamine → 1,4-Dimethyl-3-(4-pyrrolidin-1-yl-piperidine-1-carbonyl)-6-(3-trifluoromethyl-phenyl)-1H-pyridin-2-one

HRID 1517081Notes

Reaction equation

HRID 1517081 reaction equation
[CH3:1][N:2]1[C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[CH:9]=2)=[CH:6][C:5]([CH3:18])=[C:4]([C:19](O)=[O:20])[C:3]1=[O:22].C(Cl)(=O)C(Cl)=O.CCN(CC)CC.[N:36]1([CH:41]2[CH2:46][CH2:45][NH:44][CH2:43][CH2:42]2)[CH2:40][CH2:39][CH2:38][CH2:37]1>C(Cl)Cl.CN(C=O)C>[CH3:1][N:2]1[C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[CH:9]=2)=[CH:6][C:5]([CH3:18])=[C:4]([C:19]([N:44]2[CH2:45][CH2:46][CH:41]([N:36]3[CH2:40][CH2:39][CH2:38][CH2:37]3)[CH2:42][CH2:43]2)=[O:20])[C:3]1=[O:22]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 787034-(1-Pyrrolidinyl)piperidineHCID 574411321,4-Dimethyl-2-oxo-6-(3-trifluoromethyl-phenyl)-1,2-dihydro-pyridine-3-carboxylic acid2×

Product 1

HCID 574411481,4-Dimethyl-3-(4-pyrrolidin-1-yl-piperidine-1-carbonyl)-6-(3-trifluoromethyl-phenyl)-1H-pyridin-2-oneYield 89.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of 0.16 g (0.5 mmol) of 1,4-dimethyl-2-oxo-6-(3-trifluoromethyl-phenyl)-1,2-dihydro-pyridine-3-carboxylic acid (intermediate 5) in 5 ml of CH2Cl2 was treated at RT with two drops of DMF; then, 0.05 ml=0.074 g (0.6 mmol) of oxalyl chloride was added and the reaction mixture was stirred for 30 min at RT. After removal of the solvents by evaporation in a high vacuum, the residue was dissolved again in 10 ml of CH2Cl2 and the solution was cooled down to 0° C.; then, 0.29 ml=0.21 g (2.1 mmol) of Et3N was added while stirring, followed by 0.081 g (0.5 mmol) of 4-pyrrolidin-1-yl-piperidine. The reaction mixture was subsequently warmed up to RT. After 3 hours, it was poured into crashed ice and extracted twice with CH2Cl2; the organic phases were washed with water, dried over magnesium sulfate, filtered and evaporated. The residue was purified by flash column chromatography (CH2Cl2/MeOH 98:2 to 95:5) to give 0.20 g (85%) of the title compound as light yellow solid. MS: 448.2 (MH+).

Workup

  1. customAfter removal of the solvents
  2. customby evaporation in a high vacuum
  3. dissolutionthe residue was dissolved again in 10 ml of CH2Cl2
  4. temperaturethe solution was cooled down to 0° C.
  5. stirringwhile stirring
  6. temperatureThe reaction mixture was subsequently warmed up to RT
  7. waitAfter 3 hours
  8. additionit was poured
  9. extractionextracted twice with CH2Cl2
  10. washthe organic phases were washed with water
  11. dry with materialdried over magnesium sulfate
  12. filtrationfiltered
  13. customevaporated
  14. customThe residue was purified by flash column chromatography (CH2Cl2/MeOH 98:2 to 95:5)

Sources & evidence

ORD record
ord-0fe8cc21214342158d41335d7a9b0766
Source dataset
uspto-grants-2012_07
Patent number
US08227613B2

Reaction notes

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