4-Morpholinopiperidine → Methyl 7-(ethyloxy)-6-(methylsulfonyl)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate

HRID 245177Notes

Reaction equation

HRID 245177 reaction equation
Br[CH2:2][C:3]1[C:4]([C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[CH:25]=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])=[C:8]([O:21][CH2:22][CH3:23])[CH:7]=2.[NH:34]1[CH2:39][CH2:38][CH:37]([N:40]2[CH2:45][CH2:44][O:43][CH2:42][CH2:41]2)[CH2:36][CH2:35]1>C(#N)C>[CH2:22]([O:21][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:34]3[CH2:39][CH2:38][CH:37]([N:40]4[CH2:45][CH2:44][O:43][CH2:42][CH2:41]4)[CH2:36][CH2:35]3)[C:4]([C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[CH:25]=3)=[N:5]2)=[CH:10][C:9]=1[S:17]([CH3:20])(=[O:19])=[O:18])[CH3:23]

Participants

4

Reactant 2

HCID 7957244-MorpholinopiperidineHCID 67383491Methyl 3-(bromomethyl)-7-(ethyloxy)-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate

Product 1

HCID 67417923Methyl 7-(ethyloxy)-6-(methylsulfonyl)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylateYield 78%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A suspension of methyl 3-(bromomethyl)-7-(ethyloxy)-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (1.705 g, 3.12 mmol) and -(4-piperidinyl)morpholine (0.691 g, 4.06 mmol) in acetonitrile (30 mL) was stirred for 3 h. The solvent was removed under reduced pressure, and the residue was dissolved in DMSO 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 were extracted with methylene chloride (three times). The combined organic extracts were washed with brine (two times), dried over Na2SO4, filtered, and concentrated in vacuo to afford methyl 7-(ethyloxy)-6-(methylsulfonyl)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (1.54 g, 78% yield). 1H NMR (400 MHz, DMSO-d6) δ8.40 (s, 1H), 7.98 (s, 1H), 7.87-7.94 (m, 2H), 7.76-7.81 (m, 2H), 4.40 (q, J=6.94 Hz, 2H), 4.01 (s, 3H), 3.61 (s, 2H), 3.53 (br. s., 4H), 3.42 (s, 3H), 2.62 (d, J=11.29 Hz, 2H), 2.38 (br. s., 4H), 1.93-2.05 (m, 1H), 1.81 (t, J=11.04 Hz, 2H), 1.62 (d, J=12.05 Hz, 2H), 1.47 (t, J=6.90 Hz, 3H), 1.18-1.30 (m, 2H); MS (m/z) 636.2 (M+H+).

Workup

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

Sources & evidence

ORD record
ord-cccb9516106e42729cc9c514e106cc5a
Source dataset
uspto-grants-2014_02
Patent number
US08658636B2

Reaction notes

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