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

HRID 2093726ノート

反応式

HRID 2093726 の反応式
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]

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒HCID 21584119Ethylacetate methanol溶媒

反応条件

温度
120 °C

実験手順

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]+.

後処理

  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

出典と根拠

ORDレコード
ord-46a6096877f34a62933e068c9723068e
出典データセット
uspto-grants-2013_05
特許番号
US08445512B2

反応ノート

読み込み中…