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

HRID 1892044Notes

Reaction equation

HRID 1892044 reaction equation
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

Participants

10

Reactant 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

Product 1

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

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideSolvent2×HCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-52603565c39e47119937549e169673ea
Source dataset
uspto-grants-2013_08
Patent number
US08507509B2

Reaction notes

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