3-Cyclobutene-1,2-dione, 3,4-dimethoxy- → 1-[5-(2-[2-(2,2,2-Trifluoroethyl)guanidino]thiazol-4-yl)pentylamino]-2-methoxycyclobutene-3,4-dione

HRID 34808

Reaction equation

HRID 34808 reaction equation
[F:1][C:2]([F:20])([F:19])[CH2:3][N:4]=[C:5]([NH2:18])[NH:6][C:7]1[S:8][CH:9]=[C:10]([CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][NH2:17])[N:11]=1.[CH3:21][O:22][C:23]1[C:26](=O)[C:25](=[O:28])[C:24]=1[O:29]C>CO>[F:20][C:2]([F:1])([F:19])[CH2:3][N:4]=[C:5]([NH2:18])[NH:6][C:7]1[S:8][CH:9]=[C:10]([CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][NH:17][C:26]2[C:25](=[O:28])[C:24](=[O:29])[C:23]=2[O:22][CH3:21])[N:11]=1

Participants

4

Reactant 2

HCID 1232273-Cyclobutene-1,2-dione, 3,4-dimethoxy-HCID 212988612-[2-(2,2,2-Trifluoroethyl)guanidino]-4-(5-aminopentyl)thiazole

Product 1

HCID 212988131-[5-(2-[2-(2,2,2-Trifluoroethyl)guanidino]thiazol-4-yl)pentylamino]-2-methoxycyclobutene-3,4-dioneYield 40.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To 2-[2-(2,2,2-trifluoroethyl)guanidino]-4-(5-aminopentyl)thiazole (0.4 g.) in methanol (1.5 ml.) was added 1,2-dimethoxycyclobutene-3,4-dione (0.2 g.). After 2.5 hours at room temperature the mixture was evaporated to dryness, and the residue purified by preparative thin layer chromatography using methanol/chloroform 1:9 v/v as development solvent. The appropriate band was isolated to give 1-[5-(2-[2-(2,2,2-trifluoroethyl)guanidino]thiazol-4-yl)pentylamino]-2-methoxycyclobutene-3,4-dione (0.22 g.) which was dissolved in propargylamine (1 g.) and the mixture allowed to stand at room temperature overnight. The mixture was then evaporated to dryness, and the residue purified by preparative thin layer chromatography using chloroform/methanol/aqueous ammonia 90:10:1 v/v/v as developing solvent. The product from this purification was treated in methanol/acetone with excess maleic acid and the resulting salt precipitated by the addition of diethyl ether to give 1-[5-(2-[2-(2,2,2-trifluoroethyl)guanidino]thiazol-4-yl)pentylamino]-2-propargylaminocyclobutene-3,4-dione hydrogen maleate. The n.m.r. spectrum in d6 dimethylsulphoxide using tetramethylsilane as internal standard (δ=0) included the following resonances (δ): 1.5 (multiplet, 6H); 3.3 (singlet, 1H); 3.5 (multiplet, 2H); 4.1 (quartet, 2H); 4.8 (quartet, 2H); 6.6 (singlet, 1H).

Workup

  1. customAfter 2.5 hours at room temperature the mixture was evaporated to dryness
  2. customthe residue purified by preparative thin layer chromatography
  3. customThe appropriate band was isolated

Sources & evidence

ORD record
ord-7253d6d59b9a426b80bf9f7f561e6c6d
Source dataset
uspto-grants-1988_08
Patent number
US04762932

Linked notes

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