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Potassium Carbonate → 4-[(4-Fluoro-2-methylindol-5-yl)oxy]-6-methoxy-7-(3-[4-(2-propynyl)piperazin-1-yl]propoxy}quinazoline

HRID 916440
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HRID 916440 반응식
OC(C(F)(F)F)=O.OC(C(F)(F)F)=O.[CH2:15]([N:18]1[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1)[C:16]#[CH:17].C(=O)([O-])[O-].[K+].[K+].Br[CH2:31][CH2:32][CH2:33][O:34][C:35]1[CH:44]=[C:43]2[C:38]([C:39]([O:45][C:46]3[C:47]([F:56])=[C:48]4[C:52](=[CH:53][CH:54]=3)[NH:51][C:50]([CH3:55])=[CH:49]4)=[N:40][CH:41]=[N:42]2)=[CH:37][C:36]=1[O:57][CH3:58]>CC(N(C)C)=O>[F:56][C:47]1[C:46]([O:45][C:39]2[C:38]3[C:43](=[CH:44][C:35]([O:34][CH2:33][CH2:32][CH2:31][N:21]4[CH2:22][CH2:23][N:18]([CH2:15][C:16]#[CH:17])[CH2:19][CH2:20]4)=[C:36]([O:57][CH3:58])[CH:37]=3)[N:42]=[CH:41][N:40]=2)=[CH:54][CH:53]=[C:52]2[C:48]=1[CH:49]=[C:50]([CH3:55])[NH:51]2
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참가 물질

5

반응물 3

HCID 11430Potassium CarbonateHCID 589602427-(3-Bromopropoxy)-4-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxyquinazolineHCID 872383581-Prop-2-ynylpiperazine diTFA salt

생성물 1

HCID 101744954-[(4-Fluoro-2-methylindol-5-yl)oxy]-6-methoxy-7-(3-[4-(2-propynyl)piperazin-1-yl]propoxy}quinazoline수율 73.7%

시약·촉매·용매 1

HCID 31374
Dimethylacetamide
용매

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온도
85 °C

실험 절차

1-Prop-2-ynylpiperazine diTFA salt (329 mg, 0.94 mmol) and potassium carbonate (258 mg, 1.87 mmol) were added to a solution of 7-(3-bromopropoxy)-4-[(4-fluoro-2-methylindol-5-yl)oxy]-6-methoxyquinazoline (144 mg, 0.31 mmol), (prepared as described for the starting material in Example 7), in DMA (3.6 ml). The reaction mixture was stirred at 85° C. overnight before being filtered. The filtrate was concentrated under vacuum and the crude product was purified by column chromatography eluting with increasingly polar mixtures of ammonia/methanol in methylene chloride (1 to 7%). A second purification by column chromatography eluting with a mixture of methanol in methylene chloride (1/9) gave 4-[(4-fluoro-2-methylindol-5-yl)oxy]-6-methoxy-7-(3-[4-(2-propynyl)piperazin-1-yl]propoxy}quinazoline as a white solid (115 mg, 73%).

후처리

  1. custom(prepared
  2. filtrationbefore being filtered
  3. concentrationThe filtrate was concentrated under vacuum
  4. customthe crude product was purified by column chromatography
  5. washeluting
  6. temperaturewith increasingly polar mixtures of ammonia/methanol in methylene chloride (1 to 7%)
  7. customA second purification by column chromatography
  8. washeluting with a mixture of methanol in methylene chloride (1/9)

출처 및 근거

ORD 기록
ord-880e3c6e4dd94a8f9d16c337768b200b
출처 데이터셋
uspto-grants-2007_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07268230B2

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