Diisopropylethylamine → Methyl 6-(methylsulfonyl)-3-[(4-oxo-1-piperidinyl)methyl]-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate

HRID 245254Notes

Reaction equation

HRID 245254 reaction equation
Br[CH2:2][C:3]1[C:4]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=2)=[N:5][C:6]2[C:11]([C:12]=1[C:13]([O:15][CH3:16])=[O:14])=[CH:10][C:9]([S:17]([CH3:20])(=[O:19])=[O:18])=[CH:8][CH:7]=2.Cl.[NH:32]1[CH2:37][CH2:36][C:35](=[O:38])[CH2:34][CH2:33]1.C(N(CC)C(C)C)(C)C>C(#N)C>[CH3:20][S:17]([C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[N:5]=[C:4]([C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:28])([F:29])[F:30])[CH:22]=1)[C:3]([CH2:2][N:32]1[CH2:37][CH2:36][C:35](=[O:38])[CH2:34][CH2:33]1)=[C:12]2[C:13]([O:15][CH3:16])=[O:14])(=[O:19])=[O:18]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 30848514-Piperidone hydrochlorideHCID 67383823Methyl 3-(bromomethyl)-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate

Product 1

HCID 67417193Methyl 6-(methylsulfonyl)-3-[(4-oxo-1-piperidinyl)methyl]-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylateYield 51%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Methyl 3-(bromomethyl)-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (2 g, 3.98 mmol), 4-piperidone HCl salt (0.648 g, 4.78 mmol), N,N-diisopropylethylamine (1.53 mL, 8.76 mmol) in acetonitrile (13.27 mL) was heated to 50° C. overnight. The solvent was removed under reduced pressure. The residue was diluted with Na2CO3 and extracted with methylene chloride (four times). The combined organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified via column chromatography (ISCO, 40 g silica, 5-100% ethyl acetate/hexanes) to afford methyl 6-(methylsulfonyl)-3-[(4-oxo-1-piperidinyl)methyl]-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (1.051 g, 51% yield). MS (m/z) 521.0 (M+H+).

Workup

  1. customThe solvent was removed under reduced pressure
  2. additionThe residue was diluted with Na2CO3
  3. extractionextracted with methylene chloride (four times)
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified via column chromatography (ISCO, 40 g silica, 5-100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-55280d9ba05a4b73be0c7c634cfcbde9
Source dataset
uspto-grants-2014_02
Patent number
US08658636B2

Reaction notes

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