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 1902311Notes

Reaction equation

HRID 1902311 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 developing 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-b2199548c43248a6ba6258b7a777d5f6
Source dataset
uspto-grants-1982_12
Patent number
US04362728

Reaction notes

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