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

HRID 245186Notes

Reaction equation

HRID 245186 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]([CH3:20])(=[O:19])=[O:18])=[C:8]([O:21][CH:22]([CH3:24])[CH3:23])[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>[CH3:24][CH: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: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:33])([F:32])[F:34])[CH:26]=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 67418621Methyl 3-(bromomethyl)-7-[(1-methylethyl)oxy]-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate

Product 1

HCID 67417428Methyl 7-[(1-methylethyl)oxy]-6-(methylsulfonyl)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylateYield 80%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A suspension of methyl 3-(bromomethyl)-7-[(1-methylethyl)oxy]-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (1.732 g, 3.09 mmol) and 4-(4-piperidinyl)morpholine (0.684 g, 4.02 mmol) in acetonitrile (30 mL) was stirred for 3 h. The solvent was removed under reduced pressure, and the residue was 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-[(1-methylethyl)oxy]-6-(methylsulfonyl)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (1.6 g, 80% yield). 1H NMR (400 MHz, DMSO-d6) δ8.40 (s, 1H), 7.98 (s, 1H), 7.87-7.93 (m, 2H), 7.75-7.83 (m, 2H), 5.11 (dt, J=6.02, 12.05 Hz, 1H), 4.00 (s, 3H), 3.61 (s, 2H), 3.51-3.56 (m, 4H), 3.41 (s, 3H), 2.62 (d, J=11.29 Hz, 2H), 2.38 (br. s., 4H), 1.95-2.05 (m, 1H), 1.81 (t, J=10.92 Hz, 2H), 1.62 (d, J=12.55 Hz, 2H), 1.43 (s, 3H), 1.41 (s, 3H), 1.20-1.29 (m, 2H); MS (m/z) 650.2 (M+H+).

Workup

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

Sources & evidence

ORD record
ord-bbeba8a8e22f4f1ca7f46ef67babc1a0
Source dataset
uspto-grants-2014_02
Patent number
US08658636B2

Reaction notes

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