Sodium Hydroxide → 3-[{[4-({Cyclohexyl[2-ethyl-5-(1-hydroxy-2-methylpropyl)thiophen-3-yl]methyl}amino)phenyl]carbonyl}(methyl)amino]propanoic acid

HRID 1877273ノート

反応式

HRID 1877273 の反応式
[CH:1]1([CH:7]([NH:20][C:21]2[CH:29]=[CH:28][C:24]([C:25](O)=[O:26])=[CH:23][CH:22]=2)[C:8]2[CH:12]=[C:11]([CH:13]([OH:17])[CH:14]([CH3:16])[CH3:15])[S:10][C:9]=2[CH2:18][CH3:19])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:30][NH:31][CH2:32][CH2:33][C:34]([O:36]CC)=[O:35].O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.[Cl-].[NH4+].[OH-].[Na+]>CN(C)C=O.C(O)C.O1CCCC1.C(N(CC)CC)C>[CH:1]1([CH:7]([NH:20][C:21]2[CH:22]=[CH:23][C:24]([C:25]([N:31]([CH3:30])[CH2:32][CH2:33][C:34]([OH:36])=[O:35])=[O:26])=[CH:28][CH:29]=2)[C:8]2[CH:12]=[C:11]([CH:13]([OH:17])[CH:14]([CH3:16])[CH3:15])[S:10][C:9]=2[CH2:18][CH3:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

参加物

11

反応物 6

HCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 541480Ethyl 3-(methylamino)propanoateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 685143814-({Cyclohexyl[2-ethyl-5-(1-hydroxy-2-methylpropyl)thiophen-3-yl]methyl}amino)benzoic acid

生成物 1

HCID 595293483-[{[4-({Cyclohexyl[2-ethyl-5-(1-hydroxy-2-methylpropyl)thiophen-3-yl]methyl}amino)phenyl]carbonyl}(methyl)amino]propanoic acid収率 73%

試薬・触媒・溶媒 4

HCID 702Ethanol溶媒HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒HCID 8471Triethylamine溶媒

実験手順

To a mixture of 4-({cyclohexyl[2-ethyl-5-(1-hydroxy-2-methylpropyl)thiophen-3-yl]methyl}amino)benzoic acid (150 mg) synthesized in Example 293 (1), ethyl 3-(methylamino)propanoate (71.1 mg), 1-hydroxybenzotriazole monohydrate (83.0 mg) and triethylamine (76 μL) in N,N-dimethylformamide (10 mL) was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (104 mg), and the mixture was stirred at room temperature overnight. Saturated aqueous ammonium chloride solution was added to quench the reaction, and the mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (50% ethyl acetate/hexane) to give colorless oil. To a mixture of the obtained oil, tetrahydrofuran (5 mL) and ethanol (5 mL) was added 1N aqueous sodium hydroxide solution (1 mL), and the mixture was stirred at room temperature for 2 hr, and concentrated under reduced pressure. The residue was dissolved in water (10 mL), and 1N hydrochloric acid (1 mL) was added at 0° C. The resulting precipitate was collected by filtration to give the title compound (132 mg, 73%) as a white solid. The obtained resultant product was a mixture of two diastereomers (about 2:3).

後処理

  1. customto quench
  2. customthe reaction
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe extract was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (50% ethyl acetate/hexane)
  8. customto give colorless oil
  9. stirringthe mixture was stirred at room temperature for 2 hr
  10. concentrationconcentrated under reduced pressure
  11. dissolutionThe residue was dissolved in water (10 mL)
  12. addition1N hydrochloric acid (1 mL) was added at 0° C
  13. filtrationThe resulting precipitate was collected by filtration

出典と根拠

ORDレコード
ord-b268e1fa77d94debb87e7aa97a029ef7
出典データセット
uspto-grants-2012_11
特許番号
US08309580B2

反応ノート

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