Cesium carbonate → 2-(methoxymethyl)-8-(2-oxo-2-thiomorpholin-4-ylethoxy)-1-propyl-1H-imidazo[4,5-c]quinolin-4-amine

HRID 2203611노트

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HRID 2203611 반응식
C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:8][C:9]([N:11]1[CH2:16][CH2:15][S:14][CH2:13][CH2:12]1)=[O:10].[OH:17][C:18]1[CH:27]=[CH:26][C:25]2[N:24]=[C:23]([NH2:28])[C:22]3[N:29]=[C:30]([CH2:35][O:36][CH3:37])[N:31]([CH2:32][CH2:33][CH3:34])[C:21]=3[C:20]=2[CH:19]=1>CN(C=O)C>[CH3:37][O:36][CH2:35][C:30]1[N:31]([CH2:32][CH2:33][CH3:34])[C:21]2[C:20]3[CH:19]=[C:18]([O:17][CH2:8][C:9](=[O:10])[N:11]4[CH2:16][CH2:15][S:14][CH2:13][CH2:12]4)[CH:27]=[CH:26][C:25]=3[N:24]=[C:23]([NH2:28])[C:22]=2[N:29]=1

참가 물질

5

반응물 3

HCID 10796Cesium carbonateHCID 404242984-(Bromoacetyl) thiomorpholineHCID 689723708-hydroxy-2-methoxymethyl-1-propyl-1H-imidazo[4,5-c]quinolin-4-amine

생성물 1

HCID 588336782-(methoxymethyl)-8-(2-oxo-2-thiomorpholin-4-ylethoxy)-1-propyl-1H-imidazo[4,5-c]quinolin-4-amine

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
70 °C

실험 절차

Cesium carbonate (1.7 g, 5.22 mmol, 3 eq) was added to a mixture of 4-(bromoacetyl)thiomorpholine (468 mg, 2.09 mmol, 1.2 eq, prepared according to the method described in Part C of Example 30) and 8-hydroxy-2-methoxymethyl-1-propyl-1H-imidazo[4,5-c]quinolin-4-amine (500 mg, 1.74 mmol, 1.0 eq) in 20 mL of DMF. The reaction mixture was heated to 70° C. and maintained for 14 hours. The reaction mixture was then cooled to ambient temperature, filtered, diluted with 50 mL of dichloromethane, concentrated under reduced pressure, and filtered to afford crude material. The crude material was purified by chromatography on a HORIZON HPFC system (eluting with a gradient of methanol/dichloromethane (20:80) in dichloromethane from 0:100 to 40:60), concentrated under reduced pressure, and crystallized from acetonitrile to afford 231 mg of 2-(methoxymethyl)-8-(2-oxo-2-thiomorpholin-4-ylethoxy)-1-propyl-1H-imidazo[4,5-c]quinolin-4-amine as an off white solid, mp 214-216° C.

후처리

  1. customprepared
  2. temperaturemaintained for 14 hours
  3. temperatureThe reaction mixture was then cooled to ambient temperature
  4. filtrationfiltered
  5. additiondiluted with 50 mL of dichloromethane
  6. concentrationconcentrated under reduced pressure
  7. filtrationfiltered
  8. customto afford crude material
  9. customThe crude material was purified by chromatography on a HORIZON HPFC system (
  10. washeluting with a gradient of methanol/dichloromethane (20:80) in dichloromethane from 0:100 to 40:60),
  11. concentrationconcentrated under reduced pressure
  12. customcrystallized from acetonitrile

출처 및 근거

ORD 기록
ord-234edd689a86410aa6efad313c073628
출처 데이터셋
uspto-grants-2016_06
특허 번호
US09365567B2

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