Hydrochloric Acid → 2-(3-Bromo-quinolin-6-yloxy)-N-(1-cyano-2-hydroxy-1-methyl-ethyl)-2-methylsulfanyl acetamide

HRID 1892044ノート

反応式

HRID 1892044 の反応式
ON1C2N=CC=CC=2N=N1.CN(C)CCCN=C=NCC.Cl.[Br:23][C:24]1[CH:25]=[N:26][C:27]2[C:32]([CH:33]=1)=[CH:31][C:30]([O:34][CH:35]([S:39][CH3:40])[C:36]([OH:38])=O)=[CH:29][CH:28]=2.[NH2:41][C:42]([CH3:47])([CH2:45][OH:46])[C:43]#[N:44]>CN(C=O)C.[Cl-].[Na+].O.C(OCC)(=O)C.C(N(CC)CC)C>[Br:23][C:24]1[CH:25]=[N:26][C:27]2[C:32]([CH:33]=1)=[CH:31][C:30]([O:34][CH:35]([S:39][CH3:40])[C:36]([NH:41][C:42]([C:43]#[N:44])([CH3:47])[CH2:45][OH:46])=[O:38])=[CH:29][CH:28]=2

参加物

10

反応物 5

HCID 313Hydrochloric AcidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 181649HOAtHCID 144057522-Amino-3-hydroxy-2-methylpropanenitrileHCID 66717844(3-Bromo-quinolin-6-yloxy)-methylsulfanyl-acetic acid

生成物 1

HCID 667174052-(3-Bromo-quinolin-6-yloxy)-N-(1-cyano-2-hydroxy-1-methyl-ethyl)-2-methylsulfanyl acetamide収率 65.4%

試薬・触媒・溶媒 4

HCID 6228Dimethylformamide溶媒2 回HCID 8471Triethylamine溶媒HCID 8857Ethyl Acetate溶媒HCID 57417360Sodium chloride; water溶媒

実験手順

0.86 ml of Triethylamine, 0.672 g of 1-hydroxy-7-azabenzotriazole and 0.946 g of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide.HCl were added at R.T. to a suspension of 1.35 g of (3-bromo-quinolin-6-yloxy)-methylsulfanyl-acetic acid in 11 ml of dry DMF. To this suspension, 0.494 g of 2-amino-3-hydroxy-2-methyl-propionitrile dissolved in 2 ml of dry DMF were added dropwise. The reaction mixture was stirred 16 hrs at R.T and then poured onto a mixture of ethyl acetate and brine. The two layers were separated and the aqueous layer was extracted thrice with ethyl acetate. The organic layers were combined, washed once with brine and then dried over sodium sulphate. After filtration and concentration under reduced pressure 1.886 g of a crude mixture were isolated as a dark orange oil. The crude mixture was purified by flash chromatography on silica gel (hexane/ethyl acetate) to give 1.103 g of 2-(3-bromo-quinolin-6-yloxy)-N-(1-cyano-2-hydroxy-1-methyl-ethyl)-2-methylsulfanyl acetamide in mixture with 3-(3-bromo-quinolin-6-yl)-2-methylsulfanyl-propionic acid 2-[2-(3-bromo-quinolin-6-yloxy)-2-methylsulfanyl-acetylamino]-2-cyano-2-methyl-ethyl ester resulting from the homo coupling process.

後処理

  1. additionwere added dropwise
  2. customThe two layers were separated
  3. extractionthe aqueous layer was extracted thrice with ethyl acetate
  4. washwashed once with brine
  5. dry with materialdried over sodium sulphate
  6. filtrationAfter filtration and concentration under reduced pressure 1.886 g of a crude mixture
  7. customwere isolated as a dark orange oil
  8. customThe crude mixture was purified by flash chromatography on silica gel (hexane/ethyl acetate)

出典と根拠

ORDレコード
ord-52603565c39e47119937549e169673ea
出典データセット
uspto-grants-2013_08
特許番号
US08507509B2

反応ノート

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