Tetrahydrofuran → HCID 178481968, compound

Participants

Reaction Steps

A stirred mixture of 4.48 g. (0.015 mole) of 7-chloro-2-(1-methylhydrazino)-5-phenyl-3H-1,4-benzodiazepine (III), (prepared as in Example 1), 4.68 ml. (0.033 mole) of triethylamine and 60 ml. of tetrahydrofuran is cooled, under nitrogen, in a salt bath, and treated dropwise during about 1 hour and 20 minutes with a solution of 1.26 ml. of thiophosgene in 30 ml. of tetrahydrofuran. The mixture is allowed to warm slowly to room temperature, stand for about 16 hours and heated under reflux for about 70 minutes. The mixture, after cooling, is poured into ice water, the solid collected by filtration, dissolved in chloroform, washed with brine and dried with sodium sulfate. The aqueous filtrate is concentrated under vacuum to remove tetrahydrofuran and then extracted with chloroform. The extract is washed with brine and dried with sodium sulfate. The chloroform solutions are combined and concentrated and the residue chromatographed on 300 g. of silica gel with 2% methanol-98% chloroform. The product thus obtained is recrystallized from a mixture of methylene chloride and methanol to give a first crop weighing 1.33 g. with a melting point of 261.5° to 267° C. (with decomposition) and a second weighing 1.94 g. with a melting point of 258° to about 267° C. (with decomposition) with softening at 245° C. These two samples are apparently different polymorphic crystalline forms since they have different solubility in methylene chloride-methanol, different infrared (ir) (Nujol) absorption spectra but identical ultraviolet (uv) (EtOH) absorption spectra and nuclear magnetic resonance (nmr) (DMSO) spectra. They also show the same empirical formulae by elemental and mass spectral analysis. The second crop is recrystallized twice from methylene chloride-methanol for analysis. The analytical sample of this crop of the product, 8-chloro-1-mercapto-3-methyl-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepinium hydroxide inner salt (IV), has a melting point of 258° to 262° C. (with decomposition) with softening at 245° C.; uv (EtOH) λmax. 219.5 mμ (ε=46,100), 245 (shoulder 19,150), 260 (sh 11,250), 278 (sh 8250), 310 (sh 4200). The ir, nmr and mass spectra of the compound support its proposed structure.

Provenance & Evidence