1.2.4.5- Tetrazine-3,6-dicarboxylic ester

The only recorded synthesis of this type from a pyridazine involves the [4 + 2] cycloaddition of the lactim ether (374) with l,2,4,5-tetrazine-3,6-dicarboxylic ester, which proceeds with loss of nitrogen and methanol from the intermediate adduct to give the pyrido[2,3-t/]pyridazine (375) (77AP936). 

Tetrazine-3,6-dicarboxylic acid, 1,6-dihydro-diethyl ester... 

Dimethyl 1,2,4,5-tetrazlne-3,6-dicarboxylate s-Tetrazine-3,6-dicarboxylic acid, dimethyl ester (8) 1,2,4,5-Tetrazine-3,6-dicarboxylic acid, dimethyl ester (9) (2166-14-5)... 

DIHYDROPYRIDINE EQUIVALENT, 70, 54 Dihydroquinidine, benzoate ester, 70, 49 DIhydroquinIdIne 4-chlorobenzoate, 70, 47 Dihydroquinidine, 2-naphthoate ester, 70, 49 Dihydro-1,2,4,5-tetrazine-3,6-dicarboxylate, 70, 80 Dilsobutylaluminum hydride, 70, 20... 

The submitters employed, without purification, thionyl chloride obtained from Fisher Scientific Company. The procedure should be performed in a well-ventilated hood since thionyl chloride Is a lachrymator. The yield of dimethyl ester was found to be lower in instances when the thienyl chloride-methanol solution was not allowed to stir (30 min, -30°C) prior to the addition of dihydro-1,2,4,5-tetrazine-3,6-dicarboxylic acid. 

Seitz et al. prepared various l,2,4-triazine-C -nucleosides 340 via cycloaddition of 3,6-bis(trifluoromethyl)-l,2,4,5-tetrazine 147 to monosaccharide-derived imido esters 339 as intermediates in their quest for new pyridine C-nucleosides <1999ZNB549, 1997ZNB851, 1995AP175>. Similarly, the same group reported the preparation of novel 2-(2 -pyrrolidinyl)pyridines from (3 )- and (R)-proline via cycloaddition of 3,6-bis(trifluoromethyl)-l,2,4,5-tetrazine 147 to heterodienophilic imidates or hydrazones derived from (3)- and (R)-proline <1999TA573>. Reaction of dimethyl l,2,4,5-tetrazine-3,6-dicarboxylate 150 with either 0-methylisourea or cyanamide gave... 

When tetrazine ISO was treated with ketene 0-acetals 343 in dichloromethane at 25 °C, pyridazine-3,6-dicarboxylates 344 were obtained in 21-98% yields. In the case of the carboxamido electron-withdrawing group, further cyclization between the amide nitrogen and the ester group afforded pyrrolopyridazine 345 (Scheme 84) <2006S1513>. 

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