Diisopropylethylamine → 6-(methylsulfonyl)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[4-(trifluoromethyl)phenyl]-N-[(1R)-2,2,2-trifluoro-1-phenylethyl]-4-quinolinecarboxamide

HRID 245243Notes

Reaction equation

HRID 245243 reaction equation
[CH3:1][S:2]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[N:11]=[C:10]([C:15]1[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=1)[C:9]([CH2:25][N:26]1[CH2:31][CH2:30][CH:29]([N:32]3[CH2:37][CH2:36][O:35][CH2:34][CH2:33]3)[CH2:28][CH2:27]1)=[C:8]2[C:38]([OH:40])=O)(=[O:4])=[O:3].CCN(C(C)C)C(C)C.[F:50][C:51]([F:61])([F:60])[C@H:52]([NH2:59])[C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1.C(P1(=O)OP(=O)(CCC)OP(=O)(CCC)O1)CC>CO.CS(C)=O.CC#N.O.ClCCl>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[N:11]=[C:10]([C:15]1[CH:16]=[CH:17][C:18]([C:21]([F:23])([F:22])[F:24])=[CH:19][CH:20]=1)[C:9]([CH2:25][N:26]1[CH2:31][CH2:30][CH:29]([N:32]3[CH2:33][CH2:34][O:35][CH2:36][CH2:37]3)[CH2:28][CH2:27]1)=[C:8]2[C:38]([NH:59][C@H:52]([C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1)[C:51]([F:50])([F:60])[F:61])=[O:40])(=[O:3])=[O:4]

Participants

9

Reactant 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 11789718(alphaR)-alpha-(Trifluoromethyl)benzenemethanamineHCID 673838056-(Methylsulfonyl)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[4-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid

Product 1

HCID 534757856-(methylsulfonyl)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[4-(trifluoromethyl)phenyl]-N-[(1R)-2,2,2-trifluoro-1-phenylethyl]-4-quinolinecarboxamideYield 27%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 22036561Dimethyl sulfoxide methanolSolvent

Conditions

Temperature
0 °C

Procedure

6-(Methylsulfonyl)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[4-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (100 mg, 0.162 mmol), dichloromethane (1621 μL), DIEA (31.2 μL, 0.178 mmol), and [(1R)-2,2,2-trifluoro-1-phenylethyl]amine (37.7 mg, 0.178 mmol) were combined in a round bottom flask. The mixture was cooled to 0° C. and 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphorinane 2,4,6-trioxide (145 μL, 0.243 mmol) (50% in EtOAc) was added dropwise. The mixture was stirred at 0° C. for 2 h, warmed to room temperature, and stirred overnight. The next day 0.1 mL of water and 2 mL of CH3CN were added, and the solution was concentrated to afford a yellow residue. The residue was dissolved in MeOH/DMSO and purified by reverse phase HPLC to afford the title compound as a white solid (32 mg, 27%). MS (m/z) 735.3 (M+H+).

Workup

  1. temperaturewarmed to room temperature
  2. stirringstirred overnight
  3. concentrationthe solution was concentrated
  4. customto afford a yellow residue
  5. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-3e69005dad3d4f29a2e04f1a2c097d9d
Source dataset
uspto-grants-2014_02
Patent number
US08658636B2

Reaction notes

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