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

HRID 2268591ノート

反応式

HRID 2268591 の反応式
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]

参加物

8

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 142844-(Dimethylamino)pyridine触媒HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒2 回

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-2b200ea4024b4269aa7d460853adba34
出典データセット
uspto-grants-2001_12
特許番号
US06326386B1

反応ノート

読み込み中…