Potassium Carbonate → Cediranib

HRID 2263484노트

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HRID 2263484 반응식
[F:1][C:2]1[C:10]([O:11][C:12]2[C:21]3[C:16](=[CH:17][C:18](O)=[C:19]([O:22][CH3:23])[CH:20]=3)[N:15]=[CH:14][N:13]=2)=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([CH3:25])[NH:6]2.[C:26](=[O:29])([O-])[O-].[K+].[K+].[C:32](OC)([CH3:35])([CH3:34])C>CN1CCCC1=O>[F:1][C:2]1[C:10]([O:11][C:12]2[C:21]3[C:16](=[CH:17][C:18]([O:29][CH2:26][CH2:4][CH2:5][N:6]4[CH2:35][CH2:32][CH2:34][CH2:7]4)=[C:19]([O:22][CH3:23])[CH:20]=3)[N:15]=[CH:14][N:13]=2)=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([CH3:25])[NH:6]2

참가 물질

5

반응물 3

HCID 11430Potassium CarbonateHCID 15413tert-Butyl methyl etherHCID 1355308324-((4-Fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxyquinazolin-7-ol

생성물 1

HCID 9933475Cediranib

시약·촉매·용매 1

HCID 13387N-methyl-2-pyrrolidone용매

반응 조건

온도
80 °C

실험 절차

To a solution of 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxyquinazolin-7-ol (2.5 g) in 1-methyl-2-pyrrolidinone (25 ml) and methyl tert-butyl ether (1.8 ml) was added potassium carbonate (815 mg). The mixture was degassed by holding under vacuum and letting down with nitrogen. This was carried out five times. The mixture was heated to 80° C. and 4-azoniaspiro[3,4]octane bromide (1.75 g) was added. The mixture was maintained at 80° C. for 3.5 hours. To the hot mixture was added water (27 ml) over 2 hours. The mixture was cooled to 64° C. and the solid filtered. The solid was washed with 1:1 v/v 1-methyl-2-pyrrolidinone/water (5 ml) and then water (4×5 ml). The solid was dried in a vacuum oven to give 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazoline.

후처리

  1. customThe mixture was degassed
  2. addition4-azoniaspiro[3,4]octane bromide (1.75 g) was added
  3. temperatureThe mixture was maintained at 80° C. for 3.5 hours
  4. additionTo the hot mixture was added water (27 ml) over 2 hours
  5. temperatureThe mixture was cooled to 64° C.
  6. filtrationthe solid filtered
  7. washThe solid was washed with 1:1 v/v 1-methyl-2-pyrrolidinone/water (5 ml)
  8. customThe solid was dried in a vacuum oven

출처 및 근거

ORD 기록
ord-af4bedf7b4a14ab0adc74270cf29356d
출처 데이터셋
uspto-grants-2010_12
특허 번호
US07851623B2

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