2-Methyl-2-thiopseudourea → 2-(Methylsulfanyl)pyrimidine-4-carboxylic acid

HRID 68290

Reaction equation

HRID 68290 reaction equation
O=[C:2]([CH3:8])[C:3](=O)[C:4]([OH:6])=[O:5].CC[O-].[Na+].[CH3:13][S:14][C:15](=[NH:17])[NH2:16]>>[CH3:13][S:14][C:15]1[N:17]=[C:3]([C:4]([OH:6])=[O:5])[CH:2]=[CH:8][N:16]=1

Participants

4

Reactant 3

HCID 51422-Methyl-2-thiopseudoureaHCID 2723922Sodium ethoxideHCID 3844764Dioxobutanoic acid

Product 1

HCID 2957752-(Methylsulfanyl)pyrimidine-4-carboxylic acid

Procedure

In step a of scheme 1, reaction of the ketone with diethyl oxalacetate in the presence of a base, such as sodium ethoxide, and an organic solvent such as ethanol, provides the dioxobutanoic acid. Refluxing the dioxobutanoic acid, in step b, in the presence of a base, such as EtONa, and 2-methylisothiourea followed by and organic extraction and acid wash provides the 2-(methylthio)pyrimidine-4-carboxylic acid. In step c, the carboxylic acid is converted to the amide using standard amine coupling methodologies, such as with PyBOP or EDC, in the presence of the appropriate amine, e.g., NHRcRd. In step d, oxidation of the thiol with an oxidizing agent such as m-CPBA or H2O2 in CH3CO2H provides the sulfinyl or sulfonyl compound. In step e, reaction of the sulfinyl or sulfonyl compound with the appropriate amine, HNRaRb, in an organic solvent such as dioxane provides the compound of formula I.

Workup

  1. extractionorganic extraction and acid
  2. washwash

Sources & evidence

ORD record
ord-b02e24b78e4249d1a611d030a757bafe
Source dataset
uspto-grants-2014_09
Patent number
US08822451B2

Linked notes

Loading…