1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (R)-3-(4-{[tert-Butoxycarbonyl-(4-cyclohexylphenyl)amino]methyl}benzoylamino)-2-hydroxy-propionic acid methyl ester

HRID 967660노트

반응식

HRID 967660 반응식
[C:1]([O:5][C:6]([N:8]([CH2:21][C:22]1[CH:30]=[CH:29][C:25]([C:26](O)=[O:27])=[CH:24][CH:23]=1)[C:9]1[CH:14]=[CH:13][C:12]([CH:15]2[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]2)=[CH:11][CH:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[CH3:52][O:53][C:54](=[O:59])[C@H:55]([OH:58])[CH2:56][NH2:57]>CN(C=O)C.C(N(C(C)C)CC)(C)C.O>[CH3:52][O:53][C:54](=[O:59])[C@H:55]([OH:58])[CH2:56][NH:57][C:26](=[O:27])[C:25]1[CH:29]=[CH:30][C:22]([CH2:21][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[C:9]2[CH:10]=[CH:11][C:12]([CH:15]3[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]3)=[CH:13][CH:14]=2)=[CH:23][CH:24]=1

참가 물질

8

반응물 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 11665404methyl (2R)-3-amino-2-hydroxypropanoateHCID 223111164-{[tert-Butoxycarbonyl-(4-cyclohexylphenyl)amino]methyl}benzoic acid

생성물 1

HCID 69733520(R)-3-(4-{[tert-Butoxycarbonyl-(4-cyclohexylphenyl)amino]methyl}benzoylamino)-2-hydroxy-propionic acid methyl ester

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매2회HCID 81531Diisopropylethylamine용매

실험 절차

4-{[tert-Butoxycarbonyl-(4-cyclohexylphenyl)amino]methyl}benzoic acid was dissolved in DMF (10 mL) and HOBt (0.40 g, 2.93 mmol) and EDAC (0.52 g, 2.73 mmol) were added. The reaction mixture was stirred for 45 min. Then a solution of (R)-3-amino-2-hydroxy-propionic acid methyl ester in DMF (8 mL) and diisopropylethylamine (0.46 mL) were added. The mixture was stirred overnight. The reaction mixture was diluted with water (40 mL) and extracted with ethyl acetate (75 mL). The aqueous phase was extracted with ethyl acetate (30 mL). The combined organic phases were washed with hydrochloric acid (0.2 N, 3×30 mL), water: saturated sodium chloride (3×30 mL), dried with magnesium sulphate and concentrated in vacuo. The residue was purified by column chromatography on silica gel (100 g) using mixtures of ethyl acetate and n-heptane (1 L (1:1) and 0.5 L (7:3)) as eluents to afford 0.77 g (R)-3-(4-{[tert-butoxycarbonyl-(4-cyclohexylphenyl)amino]methyl}benzoylamino)-2-hydroxypropionic acid methyl ester.

후처리

  1. stirringThe mixture was stirred overnight
  2. extractionextracted with ethyl acetate (75 mL)
  3. extractionThe aqueous phase was extracted with ethyl acetate (30 mL)
  4. washThe combined organic phases were washed with hydrochloric acid (0.2 N, 3×30 mL), water
  5. dry with materialsaturated sodium chloride (3×30 mL), dried with magnesium sulphate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography on silica gel (100 g)

출처 및 근거

ORD 기록
ord-6dbf4085a93e4a6b848c238930d1d912
출처 데이터셋
uspto-grants-2005_10
특허 번호
US06953812B2

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