Triethylamine → 4-(5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinolin-2-yl)-piperidine-1-carboxylic acid benzyl ester

HRID 2244824노트

반응식

HRID 2244824 반응식
[NH2:1][C:2]1[C:3](=[O:14])[N:4]([CH3:13])[C:5]2[C:10]([C:11]=1[NH2:12])=[CH:9][CH:8]=[CH:7][CH:6]=2.CCN(CC)CC.[CH2:22]([O:29][C:30]([N:32]1[CH2:37][CH2:36][CH:35]([C:38](Cl)=O)[CH2:34][CH2:33]1)=[O:31])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>C(Cl)Cl>[CH2:22]([O:29][C:30]([N:32]1[CH2:37][CH2:36][CH:35]([C:38]2[NH:1][C:2]3[C:3](=[O:14])[N:4]([CH3:13])[C:5]4[CH:6]=[CH:7][CH:8]=[CH:9][C:10]=4[C:11]=3[N:12]=2)[CH2:34][CH2:33]1)=[O:31])[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1

참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 2776270Benzyl 4-(chlorocarbonyl)piperidine-1-carboxylateHCID 451232943,4-Diamino-1-methylquinolin-2(1H)-one

생성물 1

HCID 587884444-(5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinolin-2-yl)-piperidine-1-carboxylic acid benzyl ester수율 18.1%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a suspension of 3,4-diamino-1-methyl-1H-quinolin-2-one (0.60 g, 1.59 mmol) in CH2Cl2 (10 mL) were added Et3N (0.177 g, 1.74 mmol) and 4-chlorocarbonyl-piperidine-1-carboxylic acid benzyl ester (0.45 g, 1.60 mmol) at 0° C. The reaction mixture was stirred at room temperature for 1.5 h, and then excess acid chloride was quenched by addition of MeOH. The mixture was concentrated in vacuo, and the amide intermediate was taken up in 5 mL of HOAc and heated at reflux for 7 h. After cooling to room temperature, the solvent was evaporated under reduced pressure. The cyclized product was purified by flash chromatography, to give 4-(5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinolin-2-yl)-piperidine-1-carboxylic acid benzyl ester (0.12 g, 18% yield). 1H-NMR (DMSO): δ 8.08 (m, 1H), 7.60 (m, 1H), 7.43 (m, 1H), 7.32 (m, 6H), 5.02 (s, 2H), 3.91 (m, 2H), 3.34 (s, 3H), 2.81 (m, 3H), 1.78 (m, 2H), 1.39 (m, 2H). MS: calculated for C24H24N4O3+H 417.2; found: 417.4.

후처리

  1. customexcess acid chloride was quenched by addition of MeOH
  2. concentrationThe mixture was concentrated in vacuo
  3. temperatureheated
  4. temperatureat reflux for 7 h
  5. temperatureAfter cooling to room temperature
  6. customthe solvent was evaporated under reduced pressure
  7. customThe cyclized product was purified by flash chromatography

출처 및 근거

ORD 기록
ord-21401eccdb68486cb7d3f12535fff39d
출처 데이터셋
uspto-grants-2010_03
특허 번호
US07678909B1

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