1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Ethyl trans(+/-)-2-[(5-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-1,3-dihydro-2H-isoindol-2-yl)carbonyl]cyclopropanecarboxylate

HRID 1425038ノート

反応式

HRID 1425038 の反応式
[Cl:1][C:2]1[N:3]=[C:4]([C:9]([NH:11][C:12]2[CH:13]=[C:14]3[C:18](=[CH:19][CH:20]=2)[CH2:17][N:16]([C:21](OC(C)(C)C)=[O:22])[CH2:15]3)=[O:10])[NH:5][C:6]=1[CH2:7][CH3:8].Cl.C(OCC)(=O)C.[CH2:35]([O:37][C:38]([C@@H:40]1[CH2:42][C@H:41]1C(O)=O)=[O:39])[CH3:36].CCN=C=NCCCN(C)C>ClCCl.CO.CN(C1C=CN=CC=1)C>[Cl:1][C:2]1[N:3]=[C:4]([C:9]([NH:11][C:12]2[CH:13]=[C:14]3[C:18](=[CH:19][CH:20]=2)[CH2:17][N:16]([C:21]([C@@H:41]2[CH2:42][C@H:40]2[C:38]([O:37][CH2:35][CH3:36])=[O:39])=[O:22])[CH2:15]3)=[O:10])[NH:5][C:6]=1[CH2:7][CH3:8]

参加物

8

反応物 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 11535603(1R,2R)-2-(ethoxycarbonyl)cyclopropane-1-carboxylic acidHCID 21866389Hydrogen chloride-ethyl acetateHCID 67549798tert-Butyl 5-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-1,3-dihydro-2H-isoindole-2-carboxylate

生成物 1

HCID 68416710Ethyl trans(+/-)-2-[(5-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-1,3-dihydro-2H-isoindol-2-yl)carbonyl]cyclopropanecarboxylate収率 65%

試薬・触媒・溶媒 3

HCID 142844-(Dimethylamino)pyridine触媒HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒

実験手順

tert-Butyl 5-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-1,3-dihydro-2H-isoindole-2-carboxylate (described in Example (92a), 0.17 g, 0.42 mmol) was dissolved in dichloromethane (3 mL) and methanol (1 mL). A 4 N hydrochloric acid/ethyl acetate solution (15 ml, 60 mmol) was added, followed by stirring for 20 minutes. The solvent was evaporated under reduced pressure. The resulting residue was dissolved in dichloromethane (5 mL) and DMA (5 mL). trans-2-(Ethoxycarbonyl)cyclopropanecarboxylic acid (described in Wessjohann, Ludger A.; Fulhorst, Michael; Zakharova, Svetlana, Pol. J. Chem., 80, 4, 2006, 673-678, 87 mg, 0.55 mmol), WSC (191 mg, 1 mmol) and DMAP (10 mg) were added, and the mixture was stirred at room temperature for one hour. The reaction solution was concentrated, diluted with ethyl acetate, washed with water and brine, and dried over anhydrous magnesium sulfate. Following concentration under reduced pressure, the residue was purified by silica gel column chromatography (elution solvent: chloroform/methanol=95/5, 90/10) to obtain 117 mg of the title compound as a light brown solid (65%).

後処理

  1. customThe solvent was evaporated under reduced pressure
  2. dissolutionThe resulting residue was dissolved in dichloromethane (5 mL)
  3. stirringthe mixture was stirred at room temperature for one hour
  4. concentrationThe reaction solution was concentrated
  5. additiondiluted with ethyl acetate
  6. washwashed with water and brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentration under reduced pressure
  9. customthe residue was purified by silica gel column chromatography (elution solvent: chloroform/methanol=95/5, 90/10)

出典と根拠

ORDレコード
ord-eea6014b01574d34b6cefe14d051b710
出典データセット
uspto-grants-2015_01
特許番号
US08927588B2

反応ノート

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