4-Chlorobenzylamine → [1,2,3]Thiadiazolo[5,4-d]pyrimidine

Reaktionsgleichung

[S:1]1[CH:5]=[CH:4][N:3]=[N:2]1.ClC1C=CC([CH2:11][NH:12][C:13](C(C(OCC)=O)C(OCC)=O)=O)=CC=1.ClC1C=CC(C[NH2:34])=CC=1.C(C(OCC)=O)(C(OCC)=O)C(OCC)=O>>[N:3]1[C:4]2[CH:13]=[N:12][CH:11]=[N:34][C:5]=2[S:1][N:2]=1

Komponenten

Edukt 4

HCID 660364-Chlorobenzylamine

HCID 675181,2,3-Thiadiazole

HCID 80471Triethyl methanetricarboxylate

HCID 22397146Diethyl 2-(((4-Chlorobenzyl)amino)carbonyl)malonate

Produkt 1

HCID 45080540[1,2,3]Thiadiazolo[5,4-d]pyrimidine

Versuchsvorschrift

5-Hydroxy-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidine-6-carboxamides. As described in Chart BL, (4-morpholinyl)acetic acid trifluoroacetic acid salt BL.1 (J. Med. Chem. 1994, 37, 4538-4554) is cyclized to the thiadiazole BL.2 with aminoguanidine in polyphosphoric acid. Condensation of BL.2 with diethyl ethoxymethylenemalonate followed by thermal cyclization affords thiadiazolopyrimidine BL.3. The resulting ester BL.3 is then saponified to afford the corresponding acid BL.4 which is then coupled with a benzylamine (e.g. 4-chlorobenzylamine) mediated by 1,1′-carbonyldiimidazole (or other suitable carboxylic acid activating agent) to provide amides of the general formula BL.5. A specific example of heterocycle W19.2 in which R8=OH is also prepared as described in Chart BL. Thiadiazole BL.2 is heated in xylenes with diethyl 2-(((4-chlorobenzyl)amino) carbonyl)malonate (prepared by the reaction of 4-chlorobenzyl-amine with triethyl methanetricarboxylate) to afford thiadiazolopyrimidine BL.6.