1,4'-Bipiperidine → Methyl 3-(1,4'-bipiperidin-1'-ylmethyl)-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate

HRID 245156Notes

Reaction equation

HRID 245156 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.[N:31]1([CH:37]2[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]2)[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]1>C(#N)C>[N:31]1([CH:37]2[CH2:42][CH2:41][N:40]([CH2:2][C:3]3[C:4]([C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=4)=[N:5][C:6]4[C:11]([C:12]=3[C:13]([O:15][CH3:16])=[O:14])=[CH:10][C:9]([S:17]([CH3:20])(=[O:19])=[O:18])=[CH:8][CH:7]=4)[CH2:39][CH2:38]2)[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]1

Participants

4

Reactant 2

HCID 786071,4'-BipiperidineHCID 67383823Methyl 3-(bromomethyl)-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate

Product 1

HCID 71183054Methyl 3-(1,4'-bipiperidin-1'-ylmethyl)-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylateYield 145.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A suspension of methyl 3-(bromomethyl)-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (1.45 g, 2.88 mmol) and 1,4′-bipiperidine (0.630 g, 3.74 mmol) in acetonitrile (10 mL) was stirred for 3 hours. The solvent was removed under reduced pressure. The residue was dissolved in DMSO and was purified via HPLC (Biotage, 0-50% MeCN/H2O with 0.1% TFA). Fractions containing the product were neutralized with saturated aqueous NaHCO3 and extracted with methylene chloride (three times). The combined organic extracts were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to afford methyl 3-(1,4′-bipiperidin-1′-ylmethyl)-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (2.47 g, 87% yield). 1H NMR (400 MHz, DMSO-d6) δ 8.43 (d, J=1.76 Hz, 1H), 8.37 (d, J=8.78 Hz, 1H), 8.27-8.33 (m, 1H), 8.00 (s, 1H), 7.89-7.96 (m, 2H), 7.76-7.82 (m, 1H), 4.04 (s, 3H), 3.66 (s, 2H), 3.39 (s, 3H), 2.54-2.71 (m, 3H), 2.31-2.47 (m, 4H), 1.82 (br. s., 2H), 1.53 (d, J=10.04 Hz, 2H), 1.45 (br. s., 4H), 1.21-1.40 (m, 4H); MS (m/z) 590.2 (M+H+).

Workup

  1. customThe solvent was removed under reduced pressure
  2. dissolutionThe residue was dissolved in DMSO
  3. customwas purified via HPLC (Biotage, 0-50% MeCN/H2O with 0.1% TFA)
  4. additionFractions containing the product
  5. extractionextracted with methylene chloride (three times)
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-cea66b24147b491f9399867fc17d8171
Source dataset
uspto-grants-2014_02
Patent number
US08658636B2

Reaction notes

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