Hydrochloric Acid → 3-[{[4-({Cyclohexyl[2-ethyl-5-(2-methylpropanoyl)thiophen-3-yl]methyl}amino)phenyl]carbonyl}(methyl)amino]propanoic acid

HRID 1877262ノート

反応式

HRID 1877262 の反応式
[CH:1]1([CH:7]([NH:20][C:21]2[CH:29]=[CH:28][C:24]([C:25]([OH:27])=O)=[CH:23][CH:22]=2)[C:8]2[CH:12]=[C:11]([C:13](=[O: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.[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:29]=[CH:28][C:24]([C:25]([N:31]([CH3:30])[CH2:32][CH2:33][C:34]([OH:36])=[O:35])=[O:27])=[CH:23][CH:22]=2)[C:8]2[CH:12]=[C:11]([C:13](=[O:17])[CH:14]([CH3:15])[CH3:16])[S:10][C:9]=2[CH2:18][CH3:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

参加物

10

反応物 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 541480Ethyl 3-(methylamino)propanoateHCID 27960291-Hydroxybenzotriazole hydrateHCID 685154374-({Cyclohexyl[2-ethyl-5-(2-methylpropanoyl)thiophen-3-yl]methyl}amino)benzoic acid

生成物 1

HCID 595295933-[{[4-({Cyclohexyl[2-ethyl-5-(2-methylpropanoyl)thiophen-3-yl]methyl}amino)phenyl]carbonyl}(methyl)amino]propanoic acid収率 60.3%

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-(2-methylpropanoyl)thiophen-3-yl]methyl}amino)benzoic acid (139 mg) synthesized in Example 287 (8), ethyl 3-(methylamino)propanoate (53.0 mg), 1-hydroxybenzotriazole monohydrate (61.9 mg) and triethylamine (56 μL) in N,N-dimethylformamide (10 mL) 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (77.4 mg) was added, and the mixture was stirred at room temperature for 2.5 days. 1N Hydrochloric acid was added to quench the reaction, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (40% ethyl acetate/hexane), and then purified by NH-silica gel column chromatography (ethyl acetate) to give a 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 1 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 (101 mg, 60%) as a white solid.

後処理

  1. additionwas added
  2. customto quench
  3. customthe reaction
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe extract was washed with saturated brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (40% ethyl acetate/hexane)
  9. custompurified by NH-silica gel column chromatography (ethyl acetate)
  10. customto give a colorless oil
  11. stirringthe mixture was stirred at room temperature for 1 hr
  12. concentrationconcentrated under reduced pressure
  13. dissolutionThe residue was dissolved in water (10 mL)
  14. addition1N hydrochloric acid (1 mL) was added at 0° C
  15. filtrationThe resulting precipitate was collected by filtration

出典と根拠

ORDレコード
ord-eb3535fcc61c4e8e94f367de6db40e45
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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