Falnidamol, BIBX-1382, BIBX-1382BS

N4-(3-氯-4-氟-苯基)-N6-(1-甲基-4-哌啶)嘧啶并5,4-d嘧啶-4,6-二胺Chemical Name: 8-(3-Chloro-4-fluorophenylamino)-2-(1-methyl-4-piperidinylamino)pyrimido[5,4-d]pyrimidine; N8-(3-Chloro-4-fluorophenyl)-N2-(1-methyl-4-piperidinyl)pyrimido[5,4-d]pyrimidine-2,8-diamine
CAS No. 196612-93-8
项目整合开发状态: Phase I
项目研究机构: Boehringer Ingelheim (Originator)
合成路线:The reaction of 5-bromo-2-(methylsulfanyl)pyrimidine-4-carboxylic acid (I) with ammonia and CuSO4 in water gives 5-amino-2-(methylsulfanyl)pyrimidine-4-carboxylic acid (II),which is cyclized with formamide or formamidine acetate by heating at 180 C to yield 4-hydroxy-6-(methylsulfanyl)pyrimido[5,4-d]pyrimidine (III).The reaction of (III) with refluxing SOCl2 affords the corresponding 4-chloro derivative (IV),which is condensed with 3-chloro-4-fluoroaniline (V) in hot dioxane to provide the secondary amine (VI).Alternatively,(VI) can also be obtained by direct condensation of the 4-hydroxy compound (III) with aniline (V) by means of HMDS and Ts-OH at 140 ?C.The oxidation of the sulfanyl group of (VI) with MCPBA in dichloromethane provides a mixture of the sulfinyl derivative (VII) and the sulfonyl derivative (VIII),which,without isolation,is finally condensed with 1-methylpiperidin-4-amine (IX) by means of DIEA in hot DMF to give the target pyrimido-pyrimidine-diamine.