Oxalyl chloride → 4-[{3-[2-(tert-Butoxycarbonyl-pyridin-4-yl-amino)-ethoxy]-5-chloro-benzoyl}-(2-carbamoyl-phenyl)-amino]-butyric acid methyl ester

HRID 2268591노트

반응식

HRID 2268591 반응식
C(Cl)(=O)C(Cl)=O.[C:7]([O:11][C:12]([N:14]([C:28]1[CH:33]=[CH:32][N:31]=[CH:30][CH:29]=1)[CH2:15][CH2:16][O:17][C:18]1[CH:19]=[C:20]([CH:24]=[C:25]([Cl:27])[CH:26]=1)[C:21](O)=[O:22])=[O:13])([CH3:10])([CH3:9])[CH3:8].[CH3:34][O:35][C:36](=[O:50])[CH2:37][CH2:38][CH2:39][NH:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=1[C:47](=[O:49])[NH2:48].CCN(C(C)C)C(C)C>ClCCl.CN(C=O)C.CN(C1C=CN=CC=1)C>[CH3:34][O:35][C:36](=[O:50])[CH2:37][CH2:38][CH2:39][N:40]([C:21](=[O:22])[C:20]1[CH:24]=[C:25]([Cl:27])[CH:26]=[C:18]([O:17][CH2:16][CH2:15][N:14]([C:12]([O:11][C:7]([CH3:10])([CH3:8])[CH3:9])=[O:13])[C:28]2[CH:33]=[CH:32][N:31]=[CH:30][CH:29]=2)[CH:19]=1)[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=1[C:47](=[O:49])[NH2:48]

참가 물질

8

반응물 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 18348849Benzoic acid,3-chloro-5-[2-[[(1,1-dimethylethoxy)carbonyl]-4-pyridinylamino]ethoxy]-HCID 539927184-(2-Carbamoyl phenylamino)-butyric acid methyl ester

생성물 1

HCID 538483244-[{3-[2-(tert-Butoxycarbonyl-pyridin-4-yl-amino)-ethoxy]-5-chloro-benzoyl}-(2-carbamoyl-phenyl)-amino]-butyric acid methyl ester수율 33.2%

시약·촉매·용매 3

HCID 142844-(Dimethylamino)pyridine촉매HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매2회

실험 절차

2M Oxalyl chloride solution in dichloromethane (0.090 ml) and DMF (0.01 ml) were added to a suspension of 3-[2-(tert-butoxycarbonyl-pyridin-4-yl-amino)-ethoxy]-5-chloro-benzoic acid (0.060 g) in anhydrous dichloromethane (1 ml). The reaction was stirred at room temperature for 2 h then 4-(2-carbamoyl phenylamino)-butyric acid methyl ester (0.037 g), DMAP (0.002 g) and DIPEA (0.078 ml) were added. The reaction mixture was stirred at room temperature for 18 h. The reaction mixture was partitioned between ethyl acetate and water. The aqueous layer was removed and the organic phase washed with saturated aqueous sodium bicarbonate solution, water and dried with brine and over sodium sulphate and concentrated under reduced pressure. The residue was purified by flash column chromatography, eluting with ethyl acetate:cyclohexane (9:1 v/v), neat ethyl acetate and dichloromethane:methanol (9:1) to give the title compound as a colourless gum (0.031 g).

후처리

  1. stirringThe reaction mixture was stirred at room temperature for 18 h
  2. customThe reaction mixture was partitioned between ethyl acetate and water
  3. customThe aqueous layer was removed
  4. washthe organic phase washed with saturated aqueous sodium bicarbonate solution, water
  5. dry with materialdried with brine and over sodium sulphate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by flash column chromatography
  8. washeluting with ethyl acetate:cyclohexane (9:1 v/v), neat ethyl acetate and dichloromethane:methanol (9:1)

출처 및 근거

ORD 기록
ord-2b200ea4024b4269aa7d460853adba34
출처 데이터셋
uspto-grants-2001_12
특허 번호
US06326386B1

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