Potassium Carbonate → HCID 87417051, compound

HRID 731411Notes

Reaction equation

HRID 731411 reaction equation
C(S)C(O)C(O)CS.[CH:9]1([N:15]([CH:27]2[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]2)[C:16]([NH:18][C:19]2[S:20][C:21]([S:24]C#N)=[CH:22][N:23]=2)=[O:17])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1.C([O-])([O-])=O.[K+].[K+].Br[C:40]([CH3:47])([CH3:46])[C:41]([O:43][CH2:44][CH3:45])=[O:42]>CO>[CH2:44]([O:43][C:41](=[O:42])[C:40]([S:24][C:21]1[S:20][C:19]([NH:18][C:16]([N:15]([CH:9]2[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)[CH:27]2[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]2)=[O:17])=[N:23][CH:22]=1)([CH3:47])[CH3:46])[CH3:45]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 11745Propanoic acid, 2-bromo-2-methyl-, ethyl esterHCID 190011,4-Dimercapto-2,3-butanediolHCID 866111921,1-Dicyclohexyl-3-(5-thiocyanato-thiazol-2-yl)-urea

Product 1

HCID 87417051HCID 87417051, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

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.

Workup

  1. stirringThe reaction mixture was stirred at room temperature over night
  2. customquenched with water
  3. additionAddition of CH2Cl2
  4. customThe organic phase was isolated
  5. extractionthe aqueous phase was extracted with CH2Cl2
  6. concentrationthe combined organic phases were concentrated in vacuo
  7. dissolutionThe crude product was dissolved in MeCN
  8. custompurified by reverse phase preparative (HPLC method 1)

Sources & evidence

ORD record
ord-674d98b8ad1b48bdaa69c72aad4079ff
Source dataset
uspto-grants-2009_09
Patent number
US07582769B2

Reaction notes

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