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

HRID 1069645노트

반응식

HRID 1069645 반응식
[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]

참가 물질

8

반응물 4

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

생성물 1

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

시약·촉매·용매 3

HCID 962Water용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-b86e293402604d4a83c07c5e5422e1d6
출처 데이터셋
uspto-grants-2001_06
특허 번호
US06252084B1

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