Triethylamine → N-[(4-fluorophenyl)-methyl]-2-methoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylic acid amide

HRID 242119Notes

Reaction equation

HRID 242119 reaction equation
[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][NH2:7])=[CH:4][CH:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC.[CH3:41][O:42][C:43]1[C:52]([C:53](O)=[O:54])=[C:51]([CH3:56])[C:50]2[C:45](=[CH:46][C:47]([C:57]([F:60])([F:59])[F:58])=[CH:48][CH:49]=2)[N:44]=1>C1COCC1.CCOC(C)=O>[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][NH:7][C:53]([C:52]2[C:43]([O:42][CH3:41])=[N:44][C:45]3[C:50]([C:51]=2[CH3:56])=[CH:49][CH:48]=[C:47]([C:57]([F:59])([F:60])[F:58])[CH:46]=3)=[O:54])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 673264-FluorobenzylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 665836162-Methoxy-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylic acid

Product 1

HCID 56848229N-[(4-fluorophenyl)-methyl]-2-methoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylic acid amideYield 59%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

87 μl (0.8 mmol) 4-fluorobenzylamine, 266 mg (0.7 mmol) HATU and 281 μl (2.0 mmol) NEt3 were added consecutively to a solution of 199 mg (0.7 mmol) 2-methoxy-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylic acid in THF (5 ml) and the solution was then stirred for 72 h at RT. The solution was subsequently diluted with EtOAc and washed with a 4N aq. NH4Cl sol., a 1M aq. Na2CO3 sol. and brine. The organic phase was dried over MgSO4, filtered through silica gel and concentrated in a vacuum. After crystallisation (EtOAc/hexane 1:2) of the residue, 161 mg (0.4 mmol, 59%) N-[(4-fluorophenyl)-methyl]-2-methoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylic acid amide (example 5) was obtained. MS: m/z 393.1 [M+H]+.

Workup

  1. washwashed with a 4N aq. NH4Cl sol.
  2. dry with materialThe organic phase was dried over MgSO4
  3. filtrationfiltered through silica gel
  4. concentrationconcentrated in a vacuum
  5. customAfter crystallisation (EtOAc/hexane 1:2) of the residue

Sources & evidence

ORD record
ord-cfea2128046d434e8219dc697ee35368
Source dataset
uspto-grants-2014_02
Patent number
US08653101B2

Reaction notes

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