Amidinothiourea → 4-(6-(Acetamidomethyl)pyridin-2-yl)-2-guanidinothiazole

HRID 1491854Notes

Reaction equation

HRID 1491854 reaction equation
[C:1]([NH:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([C:12](=O)[CH2:13]Br)[N:7]=1)(=[O:3])[CH3:2].[NH2:16][C:17](=[N:19][C:20]([NH2:22])=[S:21])[NH2:18]>C(O)C>[C:1]([NH:4][CH2:5][C:6]1[N:7]=[C:8]([C:12]2[N:22]=[C:20]([N:19]=[C:17]([NH2:18])[NH2:16])[S:21][CH:13]=2)[CH:9]=[CH:10][CH:11]=1)(=[O:3])[CH3:2]

Participants

4

Reactant 2

HCID 2724563AmidinothioureaHCID 10445869Acetamide, N-[[6-(bromoacetyl)-2-pyridinyl]methyl]-

Product 1

HCID 104469404-(6-(Acetamidomethyl)pyridin-2-yl)-2-guanidinothiazoleYield 49.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 2-(acetylaminomethyl)-6-bromoacetylpyridine (50.0 g) and diaminomethylenethiourea (15.3 g) in ethanol (400 ml) was stirred at 40° to 50° C. for 2 hours. The solvent was removed by concentration in vacuo. To the residue was added a mixture of water, ethyl acetate and tetrahydrofuran, and the mixture was adjusted to pH 9.5 with 20% aqueous potassium carbonate. The separated organic layer was washed with brine and dried over magnesium sulfate. Evaporation of the solvent gave a residue, which was purified by column chromatography on silica gel eluting with a mixture of chloroform and methanol (85:15, V/V). The eluted fractions containing the desired product were collected and evaporated in vacuo. The residue was triturated with a mixture of ethyl acetate and diisopropyl ether to give 4-(6-acetylaminomethylpyridin-2-yl)-2-(diaminomethyleneamino)thiazole (18.73 g).

Workup

  1. customThe solvent was removed by concentration in vacuo
  2. additionTo the residue was added
  3. additiona mixture of water, ethyl acetate and tetrahydrofuran
  4. washThe separated organic layer was washed with brine
  5. dry with materialdried over magnesium sulfate
  6. customEvaporation of the solvent
  7. customgave a residue, which
  8. customwas purified by column chromatography on silica gel eluting with a mixture of chloroform and methanol (85:15, V/V)
  9. additionThe eluted fractions containing the desired product
  10. customwere collected
  11. customevaporated in vacuo
  12. customThe residue was triturated with a mixture of ethyl acetate and diisopropyl ether

Sources & evidence

ORD record
ord-44e2c5376a7a48f1b3e8b6358c7aed77
Source dataset
uspto-grants-1994_12
Patent number
US05371097

Reaction notes

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