Potassium Carbonate → (5S)-6-methoxy-4-(2-methyl-1H-indol-5-yloxy)-7-(1-methyl-2-oxopyrrolidin-5-ylmethoxy)quinazoline

HRID 454315노트

반응식

HRID 454315 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][C:17]([CH3:22])=[CH:16]4)=[N:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[O:23][CH3:24].C(=O)([O-])[O-].[K+].[K+].C1(C)C=CC(S([CH2:40][C@H:41]2[N:45]([CH3:46])[C:44](=[O:47])[CH2:43][CH2:42]2)(=O)=O)=CC=1>CN(C=O)C>[CH3:24][O:23][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:2]=1[O:1][CH2:40][C@H:41]1[N:45]([CH3:46])[C:44](=[O:47])[CH2:43][CH2:42]1)[N:9]=[CH:8][N:7]=[C:6]2[O:12][C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[NH:18][C:17]([CH3:22])=[CH:16]2

참가 물질

5

반응물 3

HCID 11430Potassium CarbonateHCID 57001804(5S)-5-(p-toluenesulphonylmethyl)-1-methyl-2-pyrrolidinoneHCID 1357631087-hydroxy-6-methoxy-4-(2-methyl-1H-indol-5-yloxy)quinazoline

생성물 1

HCID 57281674(5S)-6-methoxy-4-(2-methyl-1H-indol-5-yloxy)-7-(1-methyl-2-oxopyrrolidin-5-ylmethoxy)quinazoline수율 33%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
95 °C

실험 절차

To a solution of 7-hydroxy-6-methoxy-4-(2-methyl-1H-indol-5-yloxy)quinazoline (225 mg, 0.7 mmol), (prepared as described in Example 49), in DMF was added powdered potassium carbonate (290 mg, 2.1 mmol) and (5S)-5-(p-toluenesulphonylmethyl)-1-methyl-2-pyrrolidinone (340 mg, 1.2 mmol). The reaction was then heated at 95° C. for 5 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). The product was evaporated, triturated with ether and filtered to give (5S)-6-methoxy-4-(2-methyl-1H-indol-5-yloxy)-7-(1-methyl-2-oxopyrrolidin-5-ylmethoxy)quinazoline (100 mg, 33%) as a white solid.

후처리

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

출처 및 근거

ORD 기록
ord-38a66723fb84480186985e15b40c255c
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08492560B2

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