Dimethylformamide → 2-ethyl-7-(2-morpholin-4-yl-2-oxoethoxy)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-4-amine

HRID 2203608노트

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HRID 2203608 반응식
[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:22][CH3:23])[N:14]([CH2:15][CH:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)[C:10]=2[C:9]2[CH:8]=[CH:7][C:6]([OH:24])=[CH:5][C:4]=2[N:3]=1.Br[CH2:26][C:27]([N:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1)=[O:28].C(=O)([O-])[O-].[Cs+].[Cs+].CN(C=O)C>O>[CH2:22]([C:13]1[N:14]([CH2:15][CH:16]2[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)[C:10]2[C:9]3[CH:8]=[CH:7][C:6]([O:24][CH2:26][C:27]([N:29]4[CH2:34][CH2:33][O:32][CH2:31][CH2:30]4)=[O:28])=[CH:5][C:4]=3[N:3]=[C:2]([NH2:1])[C:11]=2[N:12]=1)[CH3:23]

참가 물질

6

반응물 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 139968762-Bromo-1-(morpholin-4-yl)ethan-1-oneHCID 1363478564-amino-2-ethyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-7-ol

생성물 1

HCID 588336192-ethyl-7-(2-morpholin-4-yl-2-oxoethoxy)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-4-amine수율 52.2%

시약·촉매·용매 1

HCID 962Water용매

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온도
70 °C

실험 절차

A mixture of 4-amino-2-ethyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-7-ol (500 mg, 1.53 mmol), 2-bromo-1-(morpholin-4-yl)ethanone (351 mg, 1.69 mmol), cesium carbonate (1.5 g, 4.59 mmol) and anhydrous DMF was heated at 70° C. overnight. The reaction mixture was cooled, poured into water (350 mL), and then extracted with dichloromethane (2×100 mL). The combined organics were dried over magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was dissolved in dichloromethane and filtered. The filtrate was purified by chromatography on a HORIZON HPFC system (eluting with a gradient of 0 to 8% methanol in dichloromethane). The product was recrystallized from acetonitrile to provide 362 mg of 2-ethyl-7-(2-morpholin-4-yl-2-oxoethoxy)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-4-amine as a white powder, mp 245-247° C. Anal. calcd for C24H31N5O4: C, 63.56; H, 6.89; N, 15.44. Found: C, 63.20; H, 6.78; N, 15.31.

후처리

  1. temperatureThe reaction mixture was cooled
  2. extractionextracted with dichloromethane (2×100 mL)
  3. dry with materialThe combined organics were dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe residue was dissolved in dichloromethane
  7. filtrationfiltered
  8. customThe filtrate was purified by chromatography on a HORIZON HPFC system (
  9. washeluting with a gradient of 0 to 8% methanol in dichloromethane)
  10. customThe product was recrystallized from acetonitrile

출처 및 근거

ORD 기록
ord-d4be6540321742379fdd041fc8966b44
출처 데이터셋
uspto-grants-2016_06
특허 번호
US09365567B2

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