Réaction #818593

Équation de réaction

1,4-dithiothreitol

1,1-dicyclohexyl-3-(5-thiocyanato-thiazol-2-yl)-urea

K2CO3

ethyl 2-bromo-2-methylproprionate

→

2-[2-(3,3-dicyclohexyl-ureido)-thiazol-5-ylsulfanyl]-2-methyl-propionic acid ethyl ester

Solvants

MeOH

Conditions de réaction

Traitement

1. 1
   workup.STIRRINGThe reaction mixture was stirred at room temperature over night
2. 2
   Autrequenched with water
3. 3
   workup.ADDITIONAddition of CH2Cl2
4. 4
   AutreThe organic phase was isolated
5. 5
   Extractionthe aqueous phase was extracted with CH2Cl2
6. 6
   Concentrationthe combined organic phases were concentrated in vacuo
7. 7
   workup.DISSOLUTIONThe crude product was dissolved in MeCN
8. 8
   Autrepurified by reverse phase preparative (HPLC method 1)

Mode opératoire

An equimolar mixture of 1,4-dithiothreitol (DTT) and 1,1-dicyclohexyl-3-(5-thiocyanato-thiazol-2-yl)-urea (prepared as described in Step 1) in MeOH (4 mL/mmol) was stirred in a nitrogen atmosphere at room temperature for 2 h. Addition of K2CO3 (3 equiv) and ethyl 2-bromo-2-methylproprionate (1.1 equivalents). The reaction mixture was stirred at room temperature over night and quenched with water. Addition of CH2Cl2. The organic phase was isolated and the aqueous phase was extracted with CH2Cl2, and the combined organic phases were concentrated in vacuo. The crude product was dissolved in MeCN and purified by reverse phase preparative (HPLC method 1) to give 2-[2-(3,3-dicyclohexyl-ureido)-thiazol-5-ylsulfanyl]-2-methyl-propionic acid ethyl ester as an oil. This material was dissolved in MeOH and treated with 20 equivalents of 1N NaOH and stirred over night at room temperature. MeOH was removed by evaporation. Addition of 1N HCl to pH<1 caused precipitation. The precipitate was isolated by filtration, washed with water and dried to give the title compound.

Source