Potassium Carbonate → 2-Carbamoyl-3-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-methyl-3H-imidazole-4-carboxylic acid

HRID 900239Notes

Reaction equation

HRID 900239 reaction equation
C([O:3][C:4]([C:6]1[NH:7][C:8]([C:12]#[N:13])=[N:9][C:10]=1[CH3:11])=[O:5])C.Br[CH2:15][C:16]1[CH:20]=[C:19]([C:21]2[S:22][C:23]([Cl:26])=[CH:24][CH:25]=2)[O:18][N:17]=1.C([O-])([O-])=[O:28].[K+].[K+]>CN(C=O)C.[Cl-].[Na+].O>[C:12]([C:8]1[N:7]([CH2:15][C:16]2[CH:20]=[C:19]([C:21]3[S:22][C:23]([Cl:26])=[CH:24][CH:25]=3)[O:18][N:17]=2)[C:6]([C:4]([OH:3])=[O:5])=[C:10]([CH3:11])[N:9]=1)(=[O:28])[NH2:13]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 111501463-Bromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazoleHCID 1784703942-Cyano-5-methyl-3H-imidazole-4-carboxylic acid ethyl ester

Product 1

HCID 229398792-Carbamoyl-3-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-methyl-3H-imidazole-4-carboxylic acid

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A suspension of 194 mg 2-Cyano-5-methyl-3H-imidazole-4-carboxylic acid ethyl ester, 301 mg 3-Bromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazole and 150 mg K2CO3 in 2 ml DMF was stirred for 5 h at RT. After addition of 2 ml brine the mixture was filtered through a chem elut® cartridge by elution with ethyl acetate and then concentrated under reduced pressure. The residue was then dissolved in 5 ml THF/MeOH/water 3:1:1 and treated with 30 mg LiOH monohydrate at RT. Then the solvent was removed under reduced pressure and the residue was taken-up in 5 ml 5 M HCl. The acid precipitated as a brown solid and was dried under reduced pressure. Yield: 280 mg

Workup

  1. filtrationwas filtered through a chem elut® cartridge by elution with ethyl acetate
  2. concentrationconcentrated under reduced pressure
  3. dissolutionThe residue was then dissolved in 5 ml THF/MeOH/water 3:1:1
  4. additiontreated with 30 mg LiOH monohydrate at RT
  5. customThen the solvent was removed under reduced pressure
  6. customThe acid precipitated as a brown solid
  7. customwas dried under reduced pressure

Sources & evidence

ORD record
ord-0d555b500bd549179d8c67a5a5a922dc
Source dataset
uspto-grants-2008_04
Patent number
US07358268B2

Reaction notes

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