4-Morpholinopiperidine → HCID 67418349, compound

HRID 245217Notes

Reaction equation

HRID 245217 reaction equation
Br[CH2:2][C:3]1[C:4]([C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([F:34])([F:33])[F:32])[CH:26]=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]([CH2:20][CH3:21])(=[O:19])=[O:18])=[C:8]([O:22][CH2:23][CH3:24])[CH:7]=2.[NH:35]1[CH2:40][CH2:39][CH:38]([N:41]2[CH2:46][CH2:45][O:44][CH2:43][CH2:42]2)[CH2:37][CH2:36]1>C(#N)C>[CH2:23]([O:22][C:8]1[CH:7]=[C:6]2[C:11]([C:12]([C:13]([O:15][CH3:16])=[O:14])=[C:3]([CH2:2][N:35]3[CH2:40][CH2:39][CH:38]([N:41]4[CH2:46][CH2:45][O:44][CH2:43][CH2:42]4)[CH2:37][CH2:36]3)[C:4]([C:25]3[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([F:32])([F:34])[F:33])[CH:26]=3)=[N:5]2)=[CH:10][C:9]=1[S:17]([CH2:20][CH3:21])(=[O:18])=[O:19])[CH3:24]

Participants

4

Reactant 2

HCID 7957244-MorpholinopiperidineHCID 67383752HCID 67383752, compound

Product 1

HCID 67418349HCID 67418349, compoundYield 51%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A suspension of methyl 3-(bromomethyl)-7-(ethyloxy)-6-(ethylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (3.54 g, 6.31 mmol) and 4-(4-piperidinyl)morpholine (1.397 g, 8.20 mmol) in acetonitrile (30 mL) was stirred for 3 h. The solvent was removed under reduced pressure, and the residue was diluted with NaHCO3 and extracted with methylene chloride (three times). The combined organic extracts were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was dissolved in DMF and purified via HPLC (Biotage RP, 0-50% MeCN/H2O with 0.1% TFA). The 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 to afford methyl 7-(ethyloxy)-6-(ethylsulfonyl)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (2.09 g, 51% yield). 1H NMR (400 MHz, DMSO-d6) δ8.37 (s, 1H), 7.97 (s, 1H), 7.90 (t, J=8.53 Hz, 2H), 7.76-7.81 (m, 2H), 4.39 (q, J=6.94 Hz, 2H), 4.01 (s, 3H), 3.50-3.64 (m, 9H), 2.63 (d, J=11.29 Hz, 2H), 2.38 (br. s., 4H), 1.95-2.05 (m, 1H), 1.81 (t, J=11.17 Hz, 2H), 1.61 (d, J=11.54 Hz, 2H), 1.45 (t, J=7.03 Hz, 3H), 1.19-1.30 (m, 2H), 1.15 (t, J=7.40 Hz, 3H); MS (m/z) 650.2 (M+H+).

Workup

  1. customThe solvent was removed under reduced pressure
  2. additionthe residue was diluted with NaHCO3
  3. extractionextracted with methylene chloride (three times)
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. dissolutionThe residue was dissolved in DMF
  9. custompurified via HPLC (Biotage RP, 0-50% MeCN/H2O with 0.1% TFA)
  10. additionThe fractions containing the product
  11. extractionextracted with methylene chloride (three times)
  12. washThe combined organic extracts were washed with brine
  13. dry with materialdried over Na2SO4
  14. filtrationfiltered
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-4e8d28fc58b7426dabaf65a2e4a08238
Source dataset
uspto-grants-2014_02
Patent number
US08658636B2

Reaction notes

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