Dimethylformamide → [3-[[3-(2-amino-2-oxoethyl)-2-cyclopropyl-1-(phenylmethyl)-1H-indol-5-yl]oxy]propyl]phosphonic acid dimethyl ester

HRID 1069645ノート

反応式

HRID 1069645 の反応式
[CH:1]1([C:4]2[N:5]([CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:6]3[C:11]([C:12]=2[CH2:13][C:14]([NH2:16])=[O:15])=[CH:10][C:9]([OH:17])=[CH:8][CH:7]=3)[CH2:3][CH2:2]1.CN(C=O)C.[H-].[Na+].[CH3:32][O:33][P:34]([CH2:38][CH2:39][CH2:40]Br)(=[O:37])[O:35][CH3:36]>C1COCC1.O.C(OCC)(=O)C>[CH3:32][O:33][P:34]([CH2:38][CH2:39][CH2:40][O:17][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[N:5]([CH2:18][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)[C:4]([CH:1]1[CH2:2][CH2:3]1)=[C:12]2[CH2:13][C:14]([NH2:16])=[O:15])(=[O:37])[O:35][CH3:36]

参加物

8

反応物 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 2834991-Bromo-3-dimethoxyphosphorylpropaneHCID 106635022-cyclopropyl-5-hydroxy-1-(phenylmethyl)-1H-indole-3-acetamide

生成物 1

HCID 10600435[3-[[3-(2-amino-2-oxoethyl)-2-cyclopropyl-1-(phenylmethyl)-1H-indol-5-yl]oxy]propyl]phosphonic acid dimethyl ester収率 71%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

2-Cyclopropyl-5-hydroxy-1-(phenylmethyl)-1H-indole-3-acetamide (295 mg. 0.9 mmol) was dissolved in 10 mL of THF and 40 mL of DMF and 45 mg (1.1 mmol) of 60% NaH/mineral oil added. After 0.17 hours, 250 mg (1.1 mmol) of (3-bromopropyl)phosphonic acid dimethyl ester was added and stirring maintained for 6.5 hours. The mixture was diluted with water and ethyl acetate, the organic layer separated, washed with water, brine and dried (Na2SO4). The solution was evaporated at reduced pressure and the residue chromatographed on silica gel eluting with a gradient, 1% MeOH/methylene chloride→5% MeOH/methylene chloride, to give 280 mg (71% yield) of [3-[[3-(2-amino-2-oxoethyl)-2-cyclopropyl-1-(phenylmethyl)-1H-indol-5-yl]oxy]propyl]phosphonic acid dimethyl ester.

後処理

  1. temperaturemaintained for 6.5 hours
  2. customthe organic layer separated
  3. washwashed with water, brine
  4. dry with materialdried (Na2SO4)
  5. customThe solution was evaporated at reduced pressure
  6. customthe residue chromatographed on silica gel eluting with a gradient, 1% MeOH/methylene chloride→5% MeOH/methylene chloride

出典と根拠

ORDレコード
ord-b86e293402604d4a83c07c5e5422e1d6
出典データセット
uspto-grants-2001_06
特許番号
US06252084B1

反応ノート

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