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

HRID 1070593

Reaction equation

HRID 1070593 reaction equation
F[C:2](F)(F)[C:3](O)=O.N1(CC(O)=O)CCOCC1.[S:18]1[CH:22]=C[N:20]=[N:19]1.[C:23](N)([NH2:26])=[N:24]N.C(OC=C(C(OCC)=O)C(OCC)=O)C>>[N:20]1[C:3]2[CH:2]=[N:24][CH:23]=[N:26][C:22]=2[S:18][N:19]=1

Participants

5

Reactant 4

HCID 2146AminoguanidineHCID 6871Diethyl (ethoxymethylene)malonateHCID 675181,2,3-ThiadiazoleHCID 69732510(4-Morpholinyl)acetic acid trifluoroacetic acid salt

Product 1

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

Procedure

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-chlorobenzylamine with triethyl methanetricarboxylate) to afford thiadiazolopyrimidine BL.6.

Sources & evidence

ORD record
ord-e0b8b46c4f1c47d6a76a2bff9286f9c8
Source dataset
uspto-grants-2005_06
Patent number
US06903097B2

Linked notes

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