Benzoic acid, 3-isothiocyanato- → 1-Amino-3-(3-carboxyphenyl)-2-thioxoimidazolidin-4-one

HRID 2085358Notes

Reaction equation

HRID 2085358 reaction equation
Cl.[NH:2]([CH2:4][C:5]([O:7]CC)=O)[NH2:3].[N:10]([C:13]1[CH:14]=[C:15]([CH:19]=[CH:20][CH:21]=1)[C:16]([OH:18])=[O:17])=[C:11]=[S:12].C(N(C(C)C)CC)(C)C>ClCCl>[NH2:3][N:2]1[CH2:4][C:5](=[O:7])[N:10]([C:13]2[CH:21]=[CH:20][CH:19]=[C:15]([C:16]([OH:18])=[O:17])[CH:14]=2)[C:11]1=[S:12]

Participants

5

Reactant 3

HCID 75046Benzoic acid, 3-isothiocyanato-HCID 81531DiisopropylethylamineHCID 11593468Acetic acid, 2-hydrazinyl-, ethyl ester, hydrochloride (1:1)

Product 1

HCID 227309861-Amino-3-(3-carboxyphenyl)-2-thioxoimidazolidin-4-oneYield 51%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Ethyl hydrazinoacetate hydrochloride (155 mg, 1.00 mmol) was added to a stirred solution of 3-isothiocyanatobenzoic acid (179 mg, 1.00 mmol) and di-isopropylethylamine (523 uL, 3.00 mmol) in dichloromethane (4 mL). The mixture was stirred for 96 h, evaporated under reduced pressure and partitioned between aqueous acetic acid and ethyl acetate. The organic extracts were washed with water, saturated aqueous sodium chloride, dried (magnesium sulfate) and evaporated under reduced pressure. The residue was chromatographed (silica gel, 5-15% methanol/ethyl acetate, then 20% methanol/ethyl acetate ±0.5% acetic acid) to give 1-amino-3-(3-carboxyphenyl)-2-thioxoimidazolidin-4-one (50 mg, 51%) contaminated with 6% uncyclised by-product, suitable for the next step. A solution of 1-amino-3-(3-carboxyphenyl)-2-thioxoimidazolidin-4-one (50 mg, 0.199 mmol) and 1-(3,4-dimethylphenyl)-5-hydroxy-3-methyl-1H-pyrazole-4-carbaldehyde (55 mg, 0.239 mmol) in ethanol/methanol (2:1, 15 mL) was allowed to stand a room temperature for 96 h. The solid was filtered off, washed with ether and dried to give the title compound (42 mg, 46%) as a powder. LCMS, m/e 464 [M+H]+.

Workup

  1. customevaporated under reduced pressure
  2. custompartitioned between aqueous acetic acid and ethyl acetate
  3. washThe organic extracts were washed with water, saturated aqueous sodium chloride
  4. dry with materialdried (magnesium sulfate)
  5. customevaporated under reduced pressure
  6. customThe residue was chromatographed (silica gel, 5-15% methanol/ethyl acetate

Sources & evidence

ORD record
ord-0eac5e9eccda4d52af8e9490a4def6dd
Source dataset
uspto-grants-2004_04
Patent number
US06720345B1

Reaction notes

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