4-(3,3-Difluoropyrrolidin-1-yl)piperidine → Methyl 3-{[4-(3,3-difluoro-1-pyrrolidinyl)-1-piperidinyl]methyl}-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate

HRID 245248Notes

Reaction equation

HRID 245248 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.[F:31][C:32]1([F:43])[CH2:36][CH2:35][N:34]([CH:37]2[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]2)[CH2:33]1>C(#N)C>[F:43][C:32]1([F:31])[CH2:36][CH2:35][N:34]([CH:37]2[CH2:38][CH2:39][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)[CH2:41][CH2:42]2)[CH2:33]1

Participants

4

Reactant 2

HCID 534880204-(3,3-Difluoropyrrolidin-1-yl)piperidine2×HCID 67383823Methyl 3-(bromomethyl)-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate

Product 1

HCID 67384024Methyl 3-{[4-(3,3-difluoro-1-pyrrolidinyl)-1-piperidinyl]methyl}-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylateYield 76.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a suspension of methyl 3-(bromomethyl)-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (1.05 g, 2.090 mmol) in acetonitrile (13.94 mL) was added 4-(3,3-difluoro-1-pyrrolidinyl)piperidine (0.517 g, 2.72 mmol). After 15 h, additional 4-(3,3-difluoro-1-pyrrolidinyl)piperidine (0.188 g, 0.988 mmol, 0.47 equiv.) was added. The mixture was stirred at room temperature for 4 days. The solvent was removed, and the residue was absorbed onto florisil and purified via column chromatography (ISCO 0.5-3% methanol/methylene chloride) to give methyl 3-{[4-(3,3-difluoro-1-pyrrolidinyl)-1-piperidinyl]methyl}-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (0.976 g, 73% yield) as a yellow foam. MS (m/z) 612.2 (M+H+).

Workup

  1. customThe solvent was removed
  2. customthe residue was absorbed onto florisil
  3. custompurified via column chromatography (ISCO 0.5-3% methanol/methylene chloride)

Sources & evidence

ORD record
ord-27fd7945670a49669a873fad41197b9a
Source dataset
uspto-grants-2014_02
Patent number
US08658636B2

Reaction notes

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