BPDZ-42

Chemical Name: 3-(2-Butylamino)-4H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxide
项目整合开发状态: Preclinical
项目研究机构: Universit?Libre de Bruxelles (Originator), University of Li鑗e (Originator)
合成路线:The synthesis of the intermediates,the chiral amines (R)(-)-1,2-dimethylpropylamine (R)(-)-(I) and (S)(+)-1,2-dimethylpropylamine (S)(+)-(I) has been performed as follows:(R)(-)-1,2-Dimethylpropylamine (R)(-)-(I): The reaction of racemic 1,2-dimethylpropylamine (rac)(I) with 2(S)-(6-methoxynaphthalen-2-yl)propionic acid (S)(+)-(II) (S-naproxen) in ethanol gives the ammonium salt (III) as a diastereomeric mixture from which the (R,S)-diastereomer is obtained by successive crystallizations.Finally,this diastereomer is treated with NaOH in water to obtain the target (R)(-)-amine (R)(-)-(I).(S)(+)-1,2-Dimethylpropylamine (S)(+)-(I): The reaction of racemic 1,2-dimethylpropylamine (rac)-(I) with 2(S)-hydroxy-2-phenylacetic acid (S)(+)-(IV) (S-mandelic acid) in ethanol gives the ammonium salt (V) as a diastereomeric mixture from which the (S,S)-diastereomer is obtained by successive crystallizations.Finally,this diastereomer is treated with NaOH in water to obtain the target (S)(+)-amine (S)(+)-(I).

合成路线:The reaction of 4-hydroxypyridine-3-sulfonic acid (VI) with POCl3 and PCl5 gives 4-chloropyridine-3-sulfonyl chloride (VII),which is treated with ammonia at room temperature yielding the sulfonamide (VIII).The resulting sulfonamide (VIII) was heated with ammonia to afford 4-aminopyridine-3-sulfonamide (IX),which is cyclized with urea (X) to provide the pyridothiadiazinone (XI).The reaction of (XI) with P2S5 in pyridine gives the corresponding thione (XII),which is methylated with methyl iodide to furnish the methylsulfanyl compound (XIII).Finally,this compound (XIII) is condensed with the chiral intermediate (R)(-)-1,2-dimethylpropylamine (R)(-)-(I) to afford the chiral (R)(-)-target compound.The condensation of the intermediate methylsulfanyl compound (XIII) with the chiral intermediate (S)(+)-1,2-dimethylpropylamine (S)(+)-(I) to afford the chiral (S)(+)-target compound.

合成路线:The reaction of 4-hydroxypyridine-3-sulfonic acid (I) with POCl3 and PCl5 gives 4-chloropyridine-3-sulfonyl chloride (II),which is treated with ammonia at room temperature yielding the sulfonamide (III).The resulting sulfonamide (VIII) was heated with ammonia to afford 4-aminopyridine-3-sulfonamide (IV),which is cyclized with urea (V) to provide the pyridothiadiazinone (VI).The reaction of (XI) with P2S5 in pyridine gives the corresponding thione (VII),which is methylated with methyl iodide to furnish the methylsulfanyl compound (VII) (2).Finally,this compound (VIII) is condensed with the chiral intermediate (R)(-)-1-methylpropylamine (R)(-)-(IX) to afford the chiral (R)(-)-target compound.The condensation of the intermediate methylsulfanyl compound (VIII) with the chiral intermediate (S)(+)-1-methylpropylamine (S)(+)-(IX) to afford the chiral (S)(+)-target compound.