1-(Methylsulfonyl)piperazine → 4-(4-Fluoro-2-methylindol-5-yloxy)-7-methoxy-6-(3-(4-methylsulphonylpiperazin-1yl)propoxy)quinazoline

HRID 2068053ノート

反応式

HRID 2068053 の反応式
Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][C:15]=1[O:16][CH3:17])[N:12]=[CH:11][N:10]=[C:9]2[O:18][C:19]1[C:20]([F:29])=[C:21]2[C:25](=[CH:26][CH:27]=1)[NH:24][C:23]([CH3:28])=[CH:22]2.[CH3:30][S:31]([N:34]1[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1)(=[O:33])=[O:32]>CN(C=O)C>[F:29][C:20]1[C:19]([O:18][C:9]2[C:8]3[C:13](=[CH:14][C:15]([O:16][CH3:17])=[C:6]([O:5][CH2:4][CH2:3][CH2:2][N:37]4[CH2:38][CH2:39][N:34]([S:31]([CH3:30])(=[O:33])=[O:32])[CH2:35][CH2:36]4)[CH:7]=3)[N:12]=[CH:11][N:10]=2)=[CH:27][CH:26]=[C:25]2[C:21]=1[CH:22]=[C:23]([CH3:28])[NH:24]2

参加物

4

反応物 2

HCID 7091611-(Methylsulfonyl)piperazineHCID 589602506-(3-Bromopropoxy)-4-(4-fluoro-2-methylindol-5-yloxy)-7-methoxyquinazoline

生成物 1

HCID 670192434-(4-Fluoro-2-methylindol-5-yloxy)-7-methoxy-6-(3-(4-methylsulphonylpiperazin-1yl)propoxy)quinazoline収率 23%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
80 °C

実験手順

A solution of 6-(3-bromopropoxy)-4-(4-fluoro-2-methylindol-5-yloxy)-7-methoxyquinazoline (0.3 g, 0.652 mmol) and 1-(methylsulphonyl)piperazine (0.322 g, 1.95 mmol), (prepared as described for the starting material in Example 2), in DMF (4 ml) was stirred at 80° C. for 2.5 hours. The volatiles were removed under vacuum and the residue was purified by column chromatography eluting with increasingly polar mixtures of methylene chloride and methanol. The fractions containing the expected product were combined and evaporated. The residue was triturated under diethyl ether and the resulting solid was filtered, washed with diethyl ether and dried under vacuum to give 4-(4-fluoro-2-methylindol-5-yloxy)-7-methoxy-6-(3-(4-methylsulphonylpiperazin-1-yl)propoxy)quinazoline (0.08 g, 23%).

後処理

  1. customThe volatiles were removed under vacuum
  2. customthe residue was purified by column chromatography
  3. washeluting
  4. temperaturewith increasingly polar mixtures of methylene chloride and methanol
  5. additionThe fractions containing the expected product
  6. customevaporated
  7. customThe residue was triturated under diethyl ether
  8. filtrationthe resulting solid was filtered
  9. washwashed with diethyl ether
  10. customdried under vacuum

出典と根拠

ORDレコード
ord-8ac6bb7d8ca44efab1404f0c1094e2b3
出典データセット
uspto-grants-2012_10
特許番号
US08293902B2

反応ノート

読み込み中…