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Carbonate Ion → (5R)-4-(1H-indol-5-yloxy)-6-methoxy-7-(2-oxopyrrolidin-5-ylmethoxy)quinazoline

HRID 454318
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HRID 454318 반응식
[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([O:12][C:13]3[CH:14]=[C:15]4[C:19](=[CH:20][CH:21]=3)[NH:18][CH:17]=[CH:16]4)=[N:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[O:22][CH3:23].C(=O)([O-])[O-].C1(C)C=CC(S([CH2:37][C@@H:38]2[NH:42][C:41](=[O:43])[CH2:40][CH2:39]2)(=O)=O)=CC=1>CN(C=O)C>[NH:18]1[C:19]2[C:15](=[CH:14][C:13]([O:12][C:6]3[C:5]4[C:10](=[CH:11][C:2]([O:1][CH2:37][C@@H:38]5[NH:42][C:41](=[O:43])[CH2:40][CH2:39]5)=[C:3]([O:22][CH3:23])[CH:4]=4)[N:9]=[CH:8][N:7]=3)=[CH:21][CH:20]=2)[CH:16]=[CH:17]1
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참가 물질

5

반응물 3

HCID 19660Carbonate IonHCID 57059127(5R)-5-(p-toluenesulphonylmethyl)-2-pyrrolidinoneHCID 1357631167-hydroxy-4-(1H-indol-5-yloxy)-6-methoxyquinazoline

생성물 1

HCID 54376807(5R)-4-(1H-indol-5-yloxy)-6-methoxy-7-(2-oxopyrrolidin-5-ylmethoxy)quinazoline수율 6.7%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
90 °C

실험 절차

To a solution of 7-hydroxy-4-(1H-indol-5-yloxy)-6-methoxyquinazoline (800 mg, 2.6 mmol), (prepared as described for the starting material in Example 107), in DMF (20 ml) was added powdered potassuim carbonate (1.08 g, 7.8 mmol) and (5R)-5-(p-toluenesulphonylmethyl)-2-pyrrolidinone (1.13 g, 4.2 mmol). The reaction was then heated at 90° C. for 4 hours. The inorganic material was filtered off and the DMF removed by evaporation. The residue was then purified by chromatography eluting from methylene chloride to 12% methanol/88% methylene chloride (+1% ammonium hydroxide). A small portion was recolumned using the same gradient. The product was evaporated, triturated with ether and filtered to give (5R)-4-(1H-indol-5-yloxy)-6-methoxy-7-(2-oxopyrrolidin-5-ylmethoxy)quinazoline (70 mg, 6.5%) as a white solid.

후처리

  1. additionwas added
  2. filtrationThe inorganic material was filtered off
  3. customthe DMF removed by evaporation
  4. customThe residue was then purified by chromatography
  5. washeluting from methylene chloride to 12% methanol/88% methylene chloride (+1% ammonium hydroxide)
  6. customThe product was evaporated
  7. customtriturated with ether
  8. filtrationfiltered

출처 및 근거

ORD 기록
ord-c15b53b25d4c441b81d75b8cb74bd7d1
출처 데이터셋
uspto-grants-2013_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08492560B2

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