Dimethylformamide → 3-{4-[1-(4-Tert-butylphenyl)-3-(4-trifluoromethoxyphenyl)ureidomethyl]benzoylamino}-2-hydroxypropionic acid ethyl ester

HRID 412441노트

반응식

HRID 412441 반응식
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([CH:11]([C:27]2[CH:35]=[CH:34][CH:33]=[CH:32][C:28]=2C(O)=O)[NH:12][C:13]([NH:15][C:16]2[CH:21]=[CH:20][C:19]([O:22][C:23]([F:26])([F:25])[F:24])=[CH:18][CH:17]=2)=[O:14])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].ON1C2N=CC=CC=2N=N1.CCN=C=NCCCN(C)C.Cl.[CH2:58]([O:60][C:61](=[O:66])[CH:62]([OH:65])[CH2:63][NH2:64])[CH3:59].C(N(C(C)C)CC)(C)C.CN([CH:79]=[O:80])C>C(Cl)Cl>[CH2:58]([O:60][C:61](=[O:66])[CH:62]([OH:65])[CH2:63][NH:64][C:79](=[O:80])[C:33]1[CH:32]=[CH:28][C:27]([CH:11]([NH:12][C:13]([NH:15][C:16]2[CH:17]=[CH:18][C:19]([O:22][C:23]([F:25])([F:26])[F:24])=[CH:20][CH:21]=2)=[O:14])[C:8]2[CH:9]=[CH:10][C:5]([C:1]([CH3:2])([CH3:4])[CH3:3])=[CH:6][CH:7]=2)=[CH:35][CH:34]=1)[CH3:59]

참가 물질

8

반응물 6

HCID 6228DimethylformamideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 22311167[1-(4-Tert-butylphenyl)-3-(4-trifluoromethoxyphenyl)ureidomethyl]benzoic acidHCID 85611992(RS)-isoserine ethyl ester hydrochloride

생성물 1

HCID 674831433-{4-[1-(4-Tert-butylphenyl)-3-(4-trifluoromethoxyphenyl)ureidomethyl]benzoylamino}-2-hydroxypropionic acid ethyl ester

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of [1-(4-tert-butylphenyl)-3-(4-trifluoromethoxyphenyl)ureidomethyl]benzoic acid (1.0 g, 2.06 mmol) in DMF (1 mL) and DCM (10 mL) was added 1-hydroxy-7-azabenzo-triazole (0.33 g, 2.47 mmol). After stirring for 1 hour at room temperature, EDAC (0.47 g, 2.47 mmol), (RS)-isoserine ethyl ester hydrochloride (0.52 g, 3.09 mmol) and diisopropylethylamine (1.1 mL, 6.18 mmol) were added, successively. After stirring for 17 hours at ambient temperature the reaction mixture was partitioned between water, brine and ethyl acetate. The aqueous phase was further extracted with ethyl acetate. The combined organic phases were washed with water and brine. After drying (magnesium sulphate) and filtration, the organic phase was evaporated in vacuo. The residue was purified by column chromatography on silica gel eluting with a mixture of toluene and ethyl acetate (6:4). This afforded 1.2 g (97%) of (RS)-3-{4-[1-(4-tert-butylphenyl)-3-(4-trifluoromethoxyphenyl)ureidomethyl]-benzoylamino}-2-hydroxypropionic acid ethyl ester as an oil.

후처리

  1. stirringAfter stirring for 17 hours at ambient temperature the reaction mixture
  2. customwas partitioned between water, brine and ethyl acetate
  3. extractionThe aqueous phase was further extracted with ethyl acetate
  4. washThe combined organic phases were washed with water and brine
  5. customAfter drying
  6. filtration(magnesium sulphate) and filtration
  7. customthe organic phase was evaporated in vacuo
  8. customThe residue was purified by column chromatography on silica gel eluting with a mixture of toluene and ethyl acetate (6:4)

출처 및 근거

ORD 기록
ord-d53d1a0d06444e1d99af7a08a9c1ce3b
출처 데이터셋
uspto-grants-2003_05
특허 번호
US06562807B2

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