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

HRID 245207Notes

Reaction equation

HRID 245207 reaction equation
Br[CH2:2][C:3]1[C:4]([C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([F:35])([F:34])[F:33])[CH:27]=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]([CH:20]([CH3:22])[CH3:21])(=[O:19])=[O:18])=[C:8]([O:23][CH2:24][CH3:25])[CH:7]=2.[NH:36]1[CH2:41][CH2:40][CH:39]([N:42]2[CH2:47][CH2:46][O:45][CH2:44][CH2:43]2)[CH2:38][CH2:37]1.C(N(CC)C(C)C)(C)C>C(#N)C>[CH2:24]([O:23][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:36]3[CH2:41][CH2:40][CH:39]([N:42]4[CH2:47][CH2:46][O:45][CH2:44][CH2:43]4)[CH2:38][CH2:37]3)[C:4]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([F:35])([F:34])[F:33])[CH:27]=3)=[N:5]2)=[CH:10][C:9]=1[S:17]([CH:20]([CH3:22])[CH3:21])(=[O:19])=[O:18])[CH3:25]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 7957244-MorpholinopiperidineHCID 67384060Methyl 3-(bromomethyl)-7-(ethyloxy)-6-[(1-methylethyl)sulfonyl]-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate

Product 1

HCID 67418887Methyl 7-(ethyloxy)-6-[(1-methylethyl)sulfonyl]-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylateYield 32.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of methyl 3-(bromomethyl)-7-(ethyloxy)-6-[(1-methylethyl)sulfonyl]-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (3.5 g, 6.09 mmol), 4-(4-piperidinyl)morpholine (1.778 g, 7.31 mmol), and N,N-diisopropylethylamine (2.13 mL, 12.19 mmol) in acetonitrile (50 mL) was stirred at room temperature for 1.5 h. The solvent was removed under reduced pressure, and the residue was partitioned between a 10% sodium carbonate solution and methylene chloride. The organic phase was separated and washed with Na2CO3. The organic phase was extracted with 2N HCl (three times). The aqueous extracts were cooled in an ice bath and adjusted to pH 12 with 6N NaOH. The precipitated solid was 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-[(1-methylethyl)sulfonyl]-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (1.3 g, 31% yield) as a yellow solid. This material was used without further purification. MS (m/z) 664.2 (M+H+).

Workup

  1. customThe solvent was removed under reduced pressure
  2. customthe residue was partitioned between a 10% sodium carbonate solution and methylene chloride
  3. customThe organic phase was separated
  4. washwashed with Na2CO3
  5. extractionThe organic phase was extracted with 2N HCl (three times)
  6. temperatureThe aqueous extracts were cooled in an ice bath
  7. extractionThe precipitated solid was extracted with methylene chloride (three times)
  8. washThe combined organic extracts were washed with brine
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-02bb8659733a407fbd861af4b72a9c2c
Source dataset
uspto-grants-2014_02
Patent number
US08658636B2

Reaction notes

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