1-羟基苯并三唑(HOBT) → N-((1R)-1-(N-((1R)-2-(2-Fluorophenyl)-1-(methylcarbamoyl)ethyl)-N-methyl-carbamoyl)-2-(2-naphthyl)ethyl)-N-methylcarbamic acid tert-butylester

HRID 366194

反应方程式

HRID 366194 反应方程式
[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].ON1C2C=CC=C[C:17]=2N=N1.Cl.CN(C)CCCN=C=NCC.[F:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=1[CH2:42][C@@H:43]([NH:48][CH3:49])[C:44]([NH:46][CH3:47])=[O:45].C(N(C(C)C)CC)(C)C.C(OC(CNC([CH2:72][C:73]1[CH:82]=[CH:81][C:80]2[C:75](=[CH:76][CH:77]=[CH:78][CH:79]=2)[CH:74]=1)C(O)=O)=O)(C)(C)C.ON1C2N=CC=CC=2N=N1>C(Cl)Cl>[C:1]([O:5][C:6](=[O:7])[N:8]([C@@H:9]([C:10](=[O:12])[N:48]([C@@H:43]([C:44](=[O:45])[NH:46][CH3:47])[CH2:42][C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=1[F:35])[CH3:49])[CH2:72][C:73]1[CH:82]=[CH:81][C:80]2[C:75](=[CH:76][CH:77]=[CH:78][CH:79]=2)[CH:74]=1)[CH3:17])([CH3:2])([CH3:3])[CH3:4]

参与物

9

反应物 7

HCID 757711-羟基苯并三唑(HOBT)HCID 78288BOC-甘氨酸HCID 81531N,N-二异丙基乙胺HCID 181649N-羟基-7-氮杂苯并三氮唑HCID 27239391-乙基-(3-二甲基氨基丙基)碳酰二亚胺盐酸盐2 次HCID 223270012-(Tert-butoxycarbonylmethylamino)-3-(2-naphthyl)propionic acidHCID 54111884(2R)-3-(2-Fluorophenyl)-N-methyl-2-(methylamino)propionamide

产物 1

HCID 53671638N-((1R)-1-(N-((1R)-2-(2-Fluorophenyl)-1-(methylcarbamoyl)ethyl)-N-methyl-carbamoyl)-2-(2-naphthyl)ethyl)-N-methylcarbamic acid tert-butylester收率 69%

试剂、催化剂与溶剂 1

HCID 6344二氯甲烷溶剂3 次

实验过程

Tert-Butoxycarbonylaminoacetic acid (0.18 g; 2.39 mmol) was dissolved in methylene chloride (20 mL). 1-Hydroxybenzotriazole (0.32 g; 2.39 mmol) and N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (0.55 g; 2.87 mmol) were added and the reaction mixture was stirred for 15 min at room temperature. (2R)-3-(2-Fluorophenyl)-N-methyl-2-(methylamino)propionamide (1.0 g; 4.78 mmol) and diisopropylethylamine (0.9 mL; 5.26 mmol) was added and the reaction mixture was stirred for 12 hours at room temperature. A mixture of 2-(tert-butoxycarbonylmethylamino)-3-(2-naphthyl)propionic acid (0.78 g; 2.39 mmol), 1-hydroxy-7-azabenzotriazole (0.33 g; 2.39 mmol) and N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (0.55 g; 2.87 mmol) were dissolved in methylene chloride (20 mL) and added to the reaction mixture. The reaction mixture was stirred for 12 hours at room temperature. Methylene chloride (50 mL) was added and the reaction mixture was washed with water (30 mL), an aqueous solution of sodium hydrogen sulfate (10%; 30 mL), an aqueous solution of sodium hydrogen carbonate/sodium carbonate (pH 9; 30 mL) and water (30 mL) and dried (magnesium sulfate). The solvent was removed in vacuo and the residue was chromatographed on silica (2.5×30 cm) using ethyl acetate/heptane (2:1) as eluent to afford 0.86 g of N-((1R)-1-(N-((1R)-2-(2-fluorophenyl)-1-(methylcarbamoyl)ethyl)-N-methylcarbamoyl)-2-(2-naphthyl)ethyl)-N-methyl-carbamic acid tert-butylester.

后处理

  1. stirringthe reaction mixture was stirred for 12 hours at room temperature
  2. additionadded to the reaction mixture
  3. stirringThe reaction mixture was stirred for 12 hours at room temperature
  4. washthe reaction mixture was washed with water (30 mL)
  5. dry with materialan aqueous solution of sodium hydrogen sulfate (10%; 30 mL), an aqueous solution of sodium hydrogen carbonate/sodium carbonate (pH 9; 30 mL) and water (30 mL) and dried (magnesium sulfate)
  6. customThe solvent was removed in vacuo
  7. customthe residue was chromatographed on silica (2.5×30 cm)

来源与证据

ORD记录
ord-b7f07d609a0d482bab4ae05f7823e7e8
来源数据集
uspto-grants-2000_10
专利号
US06127391

关联笔记

加载中…