Dimethylformamide → N-[(1-Phenylindole-2-Carbonyl)Valinyl]-3-Amino-4-Hydroxy-5-Fluoropentanoic Acid, t-Butyl Ester

HRID 2120635

反応式

HRID 2120635 の反応式
CCN=C=NCCCN(C)C.CN(C=O)C.[C:17]1([N:23]2[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[CH:25]=[C:24]2[C:32](O)=[O:33])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[NH2:35][C@H:36]([C:40]([NH:42][CH:43]([CH:52]([OH:55])[CH2:53][F:54])[CH2:44][C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])=[O:41])[CH:37]([CH3:39])[CH3:38]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[C:17]1([N:23]2[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[CH:25]=[C:24]2[C:32]([NH:35][C@H:36]([C:40]([NH:42][CH:43]([CH:52]([OH:55])[CH2:53][F:54])[CH2:44][C:45]([O:47][C:48]([CH3:49])([CH3:50])[CH3:51])=[O:46])=[O:41])[CH:37]([CH3:38])[CH3:39])=[O:33])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

参加物

7

反応物 4

HCID 6228DimethylformamideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 6461161-Phenyl-1H-Indole-2-Carboxylic AcidHCID 86584005N-(valinyl)-3-amino-4-hydroxy-5-fluoropentanoic acid, t-butyl ester

生成物 1

HCID 86584007N-[(1-Phenylindole-2-Carbonyl)Valinyl]-3-Amino-4-Hydroxy-5-Fluoropentanoic Acid, t-Butyl Ester収率 78%

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

DMAP (122 mg, 1.0 mmol) and EDAC (249 mg, 1.3 mmol) were added as solids to a DMF solution of 1-phenylindole-2-carboxylic acid (237 mg, 1.0 mmol in 2 mL DMF), and the resultant reaction mixture was stirred for 10 minutes under a nitrogen atmosphere at 0° C. A methylene chloride solution of N-(valinyl)-3-amino-4-hydroxy-5-fluoropentanoic acid, t-butyl ester (306 mg, 1.0 mmol in 2 mL of methylene chloride) was added to the reaction mixture and the mixture was stirred for 1 hour under a nitrogen atmosphere at 0° C. and 4 hours at room temperature. The yellow reaction mixture was partitioned between ethyl acetate and 5% KHSO4 solution and the aqueous solution was back-extracted with ethyl acetate. The combined ethyl acetate solutions were washed with 5% KHSO4 solution, saturated sodium bicarbonate solution (2×) and brine, dried over sodium sulfate, and concentrated to give a colorless film (0.827 g). The film was subjected to flash chromatography on silica gel with ethyl acetate/hexanes (1:2) to yield the title product as a white foam (400 mg, 78%). TLC: (ethyl acetate/hexanes 1:1): Rf=0.27.

後処理

  1. customthe resultant reaction mixture
  2. stirringthe mixture was stirred for 1 hour under a nitrogen atmosphere at 0° C. and 4 hours at room temperature
  3. customThe yellow reaction mixture was partitioned between ethyl acetate and 5% KHSO4 solution
  4. extractionthe aqueous solution was back-extracted with ethyl acetate
  5. washThe combined ethyl acetate solutions were washed with 5% KHSO4 solution, saturated sodium bicarbonate solution (2×) and brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customto give a colorless film (0.827 g)

出典と根拠

ORDレコード
ord-6647cf90288c45c2851902f379bc4d40
出典データセット
uspto-grants-2004_02
特許番号
US06693096B2

関連ノート

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