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

HRID 2093726Notes

Reaction equation

HRID 2093726 reaction equation
C([O:3][C:4]([C:6]1[C:7]([CH2:21][N:22]([CH3:24])[CH3:23])=[N:8][C:9]2[C:14]([C:15]=1[CH3:16])=[CH:13][CH:12]=[C:11]([C:17]([F:20])([F:19])[F:18])[CH:10]=2)=O)C.C[Al](C)C.[F:29][C:30]1[CH:31]=[C:32]([CH:35]=[CH:36][CH:37]=1)[CH2:33][NH2:34].CCOC(C)=O.CCCCCC>C1(C)C=CC=CC=1.CCOC(C)=O.CO>[CH3:24][N:22]([CH2:21][C:7]1[C:6]([C:4]([NH:34][CH2:33][C:32]2[CH:35]=[CH:36][CH:37]=[C:30]([F:29])[CH:31]=2)=[O:3])=[C:15]([CH3:16])[C:14]2[C:9](=[CH:10][C:11]([C:17]([F:19])([F:20])[F:18])=[CH:12][CH:13]=2)[N:8]=1)[CH3:23]

Participants

7

Reactant 4

HCID 668533-FluorobenzylamineHCID 16682925TrimethylaluminumHCID 21226206Ethyl acetate hexaneHCID 665840092-((Dimethylamino)methyl)-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylic acid ethyl ester

Product 1

HCID 568480832-(Dimethylaminomethyl)-N-[(3-fluorophenyl)-methyl]-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylic acid amideYield 9%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 21584119Ethylacetate methanolSolvent

Conditions

Temperature
120 °C

Procedure

To a stirred solution of 530 mg (1.56 mmol) 2-((dimethylamino)methyl)-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylic acid ethyl ester in toluene (33 ml) were added 5.5 ml (2M solution in toluene, 10.9 mmol) Me3Al at RT followed by the addition of 1.77 g (15.6 mmol) 3-fluorobenzylamine. The reaction mixture was heated at 120° C. for 2 d. Then the reaction was quenched with water and acidified to pH ˜2 with conc. aq. HCl. After washing with EtoAc the aqueous layer was basified with NaOH to pH ˜11. The solution was then extracted twice with EtOAc. The combined organic layers were washed with water and brine, dried over MgSO4 and concentrated in vacuum. After CC (EtOAc/hexane 1:1->EtOAc/MeOH 9:1) of the residue, 60 mg (0.14 mmol, 9%) 2-(Dimethylaminomethyl)-N-[(3-fluorophenyl)-methyl]-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylic acid amide (example 31) were obtained. MS: m/z 420.2 [M+H]+.

Workup

  1. customThen the reaction was quenched with water
  2. washAfter washing with EtoAc the aqueous layer
  3. extractionThe solution was then extracted twice with EtOAc
  4. washThe combined organic layers were washed with water and brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuum

Sources & evidence

ORD record
ord-46a6096877f34a62933e068c9723068e
Source dataset
uspto-grants-2013_05
Patent number
US08445512B2

Reaction notes

Loading…