Dimethyl Sulfone → 1-[1-(3-amino-3-methyl-butyl)-1H-indol-5-yl]-2-methanesulphonyl-ethanone

HRID 2355244ノート

反応式

HRID 2355244 の反応式
CC(C)([O-])C.[K+].[CH3:7][S:8]([CH3:11])(=[O:10])=[O:9].[NH2:12][C:13]([CH3:30])([CH3:29])[CH2:14][CH2:15][N:16]1[C:24]2[C:19](=[CH:20][C:21]([C:25](OC)=[O:26])=[CH:22][CH:23]=2)[CH:18]=[CH:17]1.C(O)(C(F)(F)F)=O>CS(C)=O>[NH2:12][C:13]([CH3:30])([CH3:29])[CH2:14][CH2:15][N:16]1[C:24]2[C:19](=[CH:20][C:21]([C:25](=[O:26])[CH2:7][S:8]([CH3:11])(=[O:10])=[O:9])=[CH:22][CH:23]=2)[CH:18]=[CH:17]1

参加物

6

反応物 4

HCID 6213Dimethyl SulfoneHCID 6422Trifluoroacetic acidHCID 23665647Potassium tert-butoxideHCID 68453514Methyl 1-(3-amino-3-methyl-butyl)-indole-5-carboxylate

生成物 1

HCID 588751191-[1-(3-amino-3-methyl-butyl)-1H-indol-5-yl]-2-methanesulphonyl-ethanone

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒2 回

反応条件

温度
70 °C

実験手順

Potassium tert. butoxide (741 mg, 6.62 mmol) is added in two batches to a solution of dimethylsulphone (661 mg, 7.03 mmol) in 5 ml DMSO. After 10 minutes stirring at RT a solution of methyl 1-(3-amino-3-methyl-butyl)-indole-5-carboxylate (Component IV) (520 mg, 2.00 mmol) in 2 ml DMSO is added dropwise over 10 minutes. The reaction mixture is stirred for 16 hours at 70° C., acidified with TFA while cooling with ice and chromatographed on Microsorb C18-reverse-phase [acetonitrile (0.1% TFA)/water (0.13% TFA)=10:90→100:0]. Then the residue is chromatographed again on silica gel (DCM/methanol/ammonia=90:9:1).

後処理

  1. additionis added dropwise over 10 minutes
  2. temperaturewhile cooling with ice
  3. customchromatographed on Microsorb C18-reverse-phase [acetonitrile (0.1% TFA)/water (0.13% TFA)=10:90→100:0]
  4. customThen the residue is chromatographed again on silica gel (DCM/methanol/ammonia=90:9:1)

出典と根拠

ORDレコード
ord-ac0047c543f243908115cd041dabe2dc
出典データセット
uspto-grants-2010_07
特許番号
US07754756B2

反応ノート

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