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Methyl iodide → 1-(4-Fluoro-2,3-dihydroindol-1-yl)-2-(4-methoxy-6-morpholin-4-ylpyrimidin-2-yl)propan-1-one

HRID 2278585
ノート
印刷プレビュー

反応式

HRID 2278585 の反応式
[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][CH2:5][N:6]2[C:11](=[O:27])[CH2:12][C:13]1[N:18]=[C:17]([O:19][CH3:20])[CH:16]=[C:15]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[N:14]=1.[CH3:28][Si]([N-][Si](C)(C)C)(C)C.[K+].CI>O1CCCC1.[Cl-].[NH4+].C(OCC)(=O)C>[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][CH2:5][N:6]2[C:11](=[O:27])[CH:12]([C:13]1[N:18]=[C:17]([O:19][CH3:20])[CH:16]=[C:15]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[N:14]=1)[CH3:28]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 3

HCID 6328Methyl iodideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 682817151-(4-Fluoro-2,3-dihydroindol-1-yl)-2-(4-methoxy-6-morpholin-4-ylpyrimidin-2-yl)ethanone

生成物 1

HCID 682815811-(4-Fluoro-2,3-dihydroindol-1-yl)-2-(4-methoxy-6-morpholin-4-ylpyrimidin-2-yl)propan-1-one

試薬・触媒・溶媒 3

HCID 8028Tetrahydrofuran溶媒2 回
HCID 8857Ethyl Acetate溶媒
HCID 25517Ammonium Chloride溶媒

反応条件

温度
-78 °C

実験手順

300 mg of 1-(4-fluoro-2,3-dihydroindol-1-yl)-2-(4-methoxy-6-morpholin-4-yl-pyrimidin-2-yl)ethanone dissolved in 10 ml of tetrahydrofuran are cooled to −78° C. using a dry ice bath. 2.65 ml of 1N potassium bis(trimethylsilyl)amide in THF are slowly added while maintaining the temperature at −75° C. After 30 minutes of stirring, 0.125 ml of methyl iodide is added and the stirring is continued for 2 h 15. The reaction mixture is diluted with 50 ml of a saturated ammonium chloride solution and 30 ml of ethyl acetate. After settling out, the organic phase is washed with 5 times 15 ml of water, dried over magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue is purified by silica column chromatography, elution being carried out with a 99/01 mixture of dichloromethane and methanol, so as to give 215 mg of 1-(4-fluoro-2,3-dihydroindol-1-yl)-2-(4-methoxy-6-morpholin-4-ylpyrimidin-2-yl)propan-1-one in the form of a white solid, the characteristics of which are the following:

後処理

  1. temperaturewhile maintaining the temperature at −75° C
  2. waitthe stirring is continued for 2 h
  3. washthe organic phase is washed with 5 times 15 ml of water
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue is purified by silica column chromatography, elution
  8. additionbeing carried out with a 99/01 mixture of dichloromethane and methanol

出典と根拠

ORDレコード
ord-0dce945062ce47eba153b0a9ca18cfdb
出典データセット
uspto-grants-2015_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09133168B2

反応ノート

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このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート