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

HRID 2093726노트

반응식

HRID 2093726 반응식
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]

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 1140Toluene용매HCID 21584119Ethylacetate methanol용매

반응 조건

온도
120 °C

실험 절차

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]+.

후처리

  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

출처 및 근거

ORD 기록
ord-46a6096877f34a62933e068c9723068e
출처 데이터셋
uspto-grants-2013_05
특허 번호
US08445512B2

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