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

HRID 454315ノート

反応式

HRID 454315 の反応式
[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

参加物

5

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
95 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-38a66723fb84480186985e15b40c255c
出典データセット
uspto-grants-2013_07
特許番号
US08492560B2

反応ノート

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