Diisopropylethylamine → N-(2-(5-chloro-1H-indol-3-yl)ethyl)-5-(hydroxy(phenyl)methyl)isoxazole-3-carboxamide

HRID 1918748노트

반응식

HRID 1918748 반응식
[OH:1][CH:2]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:3]1[O:7][N:6]=[C:5]([C:8]([O:10]CC)=O)[CH:4]=1.Cl.[Cl:20][C:21]1[CH:22]=[C:23]2[C:27](=[CH:28][CH:29]=1)[NH:26][CH:25]=[C:24]2[CH2:30][CH2:31][NH2:32].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>O1CCCC1.[OH-].[Na+].O.CN(C=O)C.C(OCC)(=O)C>[Cl:20][C:21]1[CH:22]=[C:23]2[C:27](=[CH:28][CH:29]=1)[NH:26][CH:25]=[C:24]2[CH2:30][CH2:31][NH:32][C:8]([C:5]1[CH:4]=[C:3]([CH:2]([OH:1])[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[O:7][N:6]=1)=[O:10]

참가 물질

10

반응물 4

HCID 81531DiisopropylethylamineHCID 28274945-Chloro-1H-indole-3-ethylamine monohydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66831982Ethyl 5-(hydroxy(phenyl)methyl)isoxazole-3-carboxylate

생성물 1

HCID 66832076N-(2-(5-chloro-1H-indol-3-yl)ethyl)-5-(hydroxy(phenyl)methyl)isoxazole-3-carboxamide수율 95.6%

시약·촉매·용매 5

HCID 962Water용매2회HCID 6228Dimethylformamide용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매HCID 14798Sodium Hydroxide용매

실험 절차

A mixture of ethyl 5-(hydroxy(phenyl)methyl)isoxazole-3-carboxylate (0.534 g; 2.16 mmol) in tetrahydrofurane (6 mL) and sodium hydroxide in water (2M, 5.4 mL) was stirred at room temperature for 1 hour and diluted in water, extracted with dichloromethane and the waters acidified with HCl 6N in water to pH 2 extracted with ethyl acetate, the organic layer was dried and concentrated under reduced pressure. The residue was added to a mixture of 2-(5-chloro-1H-indol-3-yl)ethanamine hydrochloride (0.5 g; 2.16 mmol), HATU (0.822 g; 2.16 mmol), N,N diisopropylethylamine (0.932 mL; 5.41 mmol), in DMF (12 mL) and was stirred at room temperature overnight. The reaction mixture was diluted in ethyl acetate, washed with sodium disulphate, sodium carbonate and brine, dried and concentrated under reduced pressure. The crude mixture was purified by flash chromatography on silica (eluent 20 to 100% ethyl acetate in heptane) to yield 0.817 g (95%) of N-(2-(5-chloro-1H-indol-3-yl)ethyl)-5-(hydroxy(phenyl)methyl)isoxazole-3-carboxamide as a white solid.

후처리

  1. extractionextracted with dichloromethane
  2. extractionextracted with ethyl acetate
  3. customthe organic layer was dried
  4. concentrationconcentrated under reduced pressure
  5. stirringwas stirred at room temperature overnight
  6. washwashed with sodium disulphate, sodium carbonate and brine
  7. customdried
  8. concentrationconcentrated under reduced pressure
  9. customThe crude mixture was purified by flash chromatography on silica (eluent 20 to 100% ethyl acetate in heptane)

출처 및 근거

ORD 기록
ord-24c5c254e6e341df9944f04dbbd309c9
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08618138B2

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