Cesium carbonate → (R)-4-(6-bromo-2-(4-methoxybenzylamino)quinolin-3-yl)-5-methylmorpholin-3-one

HRID 1028968노트

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HRID 1028968 반응식
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([NH:12][CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=1)[C:6](I)=[CH:5]2.C(C1CCCCC1=O)(=O)C(C)C.[CH3:35][C@H:36]1[NH:41][C:40](=[O:42])[CH2:39][O:38][CH2:37]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.[Cu]I>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([NH:12][CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=1)[C:6]([N:41]1[C@H:36]([CH3:35])[CH2:37][O:38][CH2:39][C:40]1=[O:42])=[CH:5]2

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 114693012-(2-Methylpropanoyl)cyclohexan-1-oneHCID 12400352(5R)-5-methylmorpholin-3-oneHCID 673456526-bromo-3-iodo-N-(4-methoxybenzyl)quinolin-2-amine

생성물 1

HCID 67325496(R)-4-(6-bromo-2-(4-methoxybenzylamino)quinolin-3-yl)-5-methylmorpholin-3-one

시약·촉매·용매 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 6228Dimethylformamide용매

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온도
125 °C

실험 절차

A mixture of 6-bromo-3-iodo-N-(4-methoxybenzyl)quinolin-2-amine (0.25 g, 0.533 mmol, prepared as in Example 1, Step 1-2), 2-isobutyrylcyclohexanone (0.018 g, 0.107 mmol), (R)-5-methylmorpholin-3-one (0.92 g, 7.99 mmol), copper(I) iodide (5.07 mg, 0.027 mmol), and cesium carbonate (0.35 g, 1.066 mmol) in DMF (5 mL) was heated at 125° C. for 10 min. Some product was observed but mostly starting material. The mixture was heated again at 125° C. for 10 min more. This process was repeated 7× until the starting material was completely consumed. The reaction was brought to RT, poured into water (20 mL) and extracted with EtOAc. The combined organics were dried over Na2SO4, filtered, concentrated, and chromatographed on silica gel using gradient 2:1 hexanes/EtOAc to afford a light yellow solid as (R)-4-(6-bromo-2-(4-methoxybenzylamino)quinolin-3-yl)-5-methylmorpholin-3-one.

후처리

  1. temperatureThe mixture was heated again at 125° C. for 10 min more
  2. customwas completely consumed
  3. customwas brought to RT
  4. additionpoured into water (20 mL)
  5. extractionextracted with EtOAc
  6. dry with materialThe combined organics were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customchromatographed on silica gel using gradient 2:1 hexanes/EtOAc

출처 및 근거

ORD 기록
ord-79244ae5ae83428fbbc44821b2e448d8
출처 데이터셋
uspto-grants-2014_05
특허 번호
US08735384B2

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