Hydrochloric Acid → N-(4-(2-(4-(4,5-dihydro-1,3-thiazol-2-ylamino)phenyl)ethyl)-1,3-thiazol-2-yl)acetamide

HRID 1246425Notes

Reaction equation

HRID 1246425 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]2[N:11]=[C:12]([NH:15][C:16](=[O:18])[CH3:17])[S:13][CH:14]=2)=[CH:4][CH:3]=1.CS[C:21]1[S:22][CH2:23][CH2:24][N:25]=1.Cl>>[S:22]1[CH2:23][CH2:24][N:25]=[C:21]1[NH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]2[N:11]=[C:12]([NH:15][C:16](=[O:18])[CH3:17])[S:13][CH:14]=2)=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 883244,5-Dihydro-2-(methylthio)thiazoleHCID 21914814N-{4-[2-(4-aminophenyl)ethyl]thiazol-2-yl}acetamide

Product 1

HCID 21915298N-(4-(2-(4-(4,5-dihydro-1,3-thiazol-2-ylamino)phenyl)ethyl)-1,3-thiazol-2-yl)acetamideYield 20.3%

Conditions

Temperature
120 °C

Procedure

N-(4-(2-(4-Aminophenyl)ethyl)-1,3-thiazol-2-yl)acetamide (1.8 g) prepared in a similar manner according to Step 6 of Production Example 1, 2-(methylsulfanyl)-4,5-dihydro-1,3-thiazole (918 mg), hydrochloric acid concentrate (0.57 ml) and 2-methoxyethanol (28 ml) were combined under nitrogen atmosphere, and stirred at 120° C. for 10 hours. After cooled to room temperature, the reaction mixture was concentrated in vacuo. The residue was dissolved in tetrahydrofuran/water, and made basic with aqueous potassium carbonate. The mixture was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by flash column chromatography over silica gel with chloroform/methanol (30:1→20:1) as an eluent, and triturated with ethyl acetate to give N-(4-(2-(4-(4,5-dihydro-1,3-thiazol-2-ylamino)phenyl)ethyl)-1,3-thiazol-2-yl)acetamide (484.7 mg) as an off-white solid.

Workup

  1. concentrationconcentrate (0.57 ml) and 2-methoxyethanol (28 ml)
  2. temperatureAfter cooled to room temperature
  3. concentrationthe reaction mixture was concentrated in vacuo
  4. dissolutionThe residue was dissolved in tetrahydrofuran/water
  5. extractionThe mixture was extracted with ethyl acetate
  6. dry with materialThe organic layer was dried over magnesium sulfate
  7. customevaporated in vacuo
  8. customThe residue was purified by flash column chromatography over silica gel with chloroform/methanol (30:1→20:1) as an eluent
  9. customtriturated with ethyl acetate

Sources & evidence

ORD record
ord-99c6ee4e506344cea1d4dbac51bc2821
Source dataset
uspto-grants-2006_10
Patent number
US07125901B2

Reaction notes

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