Water → HCID 178495982, compound

HRID 1734024Notes

Reaction equation

HRID 1734024 reaction equation
[Cl:1][C:2]([O:4][CH3:5])=[O:3].Cl.Cl.[NH2:8][CH2:9][C:10]1[CH:11]=[C:12]([C:16]2[N:17]=[C:18]([N:21]=[C:22]([NH2:28])[NH:23][CH2:24][CH2:25][O:26][CH3:27])[S:19][CH:20]=2)[CH:13]=[CH:14][CH:15]=1.C(N(CC)CC)C.O>CN(C)C=O.O1CCCC1>[ClH:1].[NH2:28][C:22](=[N:21][C:18]1[S:19][CH:20]=[C:16]([C:12]2[CH:13]=[CH:14][CH:15]=[C:10]([CH2:9][NH:8][C:2]([O:4][CH3:5])=[O:3])[CH:11]=2)[N:17]=1)[NH:23][CH2:24][CH2:25][O:26][CH3:27]

Participants

7

Reactant 4

HCID 962WaterHCID 6586Methyl chloroformateHCID 8471TriethylamineHCID 178495975HCID 178495975, compound

Product 1

HCID 178495982HCID 178495982, compoundYield 27.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

Methyl chloroformate (0.45 g) was added slowly to a suspension of 4-(3-aminomethylphenyl)-2-[[(amino)(2-methoxyethylamino)methylene]amino] thiazole dihydrochloride (1.5 g) and triethylamine (1.6 g) in N,N-dimethylformamide (10 ml) and tetrahydrofuran (10 ml) with cooling on an ice bath. The mixture was stirred at room temperature for 8 hours. Water (100 ml) was added to the mixture. The mixture was extracted with a mixture of ethyl acetate (200 ml) and tetahydrofuran (20 ml). The extract was dried with magnesium sulfate and then evaporated in vacuo. The residue was chromatographed on a silica gel column eluting with a mixture of chloroform and methanol (20:1). The solvent was removed under reduced pressure and the residue was dissolved in ethanol (20 ml). 4N-Dioxane solution of hydrogen chloride (5 ml) was added to the mixture. The mixture was stirred at room temperature for 30 minutes. The solvent was removed under reduced pressure. The residue was crystallized from a mixture of ethanol and diisopropyl ether. Recrystallization from a mixture of ethanol and diisopropyl ether afforded 2-[[(amino)(2-methoxyethylamino)methylene]amino]-4-(3-methoxycarbonylaminomethylphenyl)thiazole hydrochloride (0.43 g).

Workup

  1. temperaturewith cooling on an ice bath
  2. extractionThe mixture was extracted with a mixture of ethyl acetate (200 ml) and tetahydrofuran (20 ml)
  3. dry with materialThe extract was dried with magnesium sulfate
  4. customevaporated in vacuo
  5. customThe residue was chromatographed on a silica gel column
  6. washeluting with a mixture of chloroform and methanol (20:1)
  7. customThe solvent was removed under reduced pressure
  8. dissolutionthe residue was dissolved in ethanol (20 ml)
  9. addition4N-Dioxane solution of hydrogen chloride (5 ml) was added to the mixture
  10. stirringThe mixture was stirred at room temperature for 30 minutes
  11. customThe solvent was removed under reduced pressure
  12. customThe residue was crystallized from a mixture of ethanol and diisopropyl ether
  13. customRecrystallization
  14. additionfrom a mixture of ethanol and diisopropyl ether

Sources & evidence

ORD record
ord-86cb96cffd2045c2a6a5cf9ec21aee65
Source dataset
uspto-grants-1996_07
Patent number
US05532258

Reaction notes

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