Pipemidic acid

Chemicei Name 1 /2-Diphenyl-3,5 dioxo-4-n-butyl-4-(N -methylpiperazinomethyI)pyrazoli- 

77 g (0.25 mol) of phenylbutazone, 30 ml of a 30% strength solution of formaldehyde and 50 ml of ethyl alcohol are introduced into a 500 ml flask, 25 g (0.25 mol) of N-methylpiper-azine are slowly added to this mixture which is stirred mechanically. The mixture is then heated for one hour on a water bath, left to cool, and crystallization started by scratching. 

After being left in the refrigerator overnight the mixture, which has set solid, is triturated with 50 ml of isopropyl alcohol and the solid product filtered off and dried in vacuo over phosphorus pentoxide. 63 g (60% yield) of 1,2-diphenyl-3,5-dioxo-4-n-butyl-4-(N -methylpiper-azinomethyl)pyrazolidine are obtained, melting at 1 29°C after recrystallization from 150 ml of isopropyl alcohol. 

Chemical Name 8-ethyl-5,8-dihydro-5-oxo-2-(1-piperazinyl)pyrido[2,3-d] pyrimidine-6-carboxylic acid 

Trade Name Manufacturer Country Year Introduced 

---

Many of these reactions occur in the course of synthesis of fully or partly unsaturated products after initial ring closure, giving rise to more unsaturated systems, e.g. in the pyrido[2,3-their derivatives, e.g. (16a) -> (17) (74JAP(K)7444000). Examples are also found in the pyrido[3,2-[Pg.205]

The 4-piperazinyl nitrogen in pipemidic acid (69) has been alkylated, acylated and sulfonylated in the search for enhanced antibacterial activity, whilst the 3-pyrrolidinyl position in piromidic acid (68) is hydroxylated metabolically and enzymically to (74) (75MI21503), from which acyloxy derivatives have been prepared. 

In the 2-position, the methylthio derivatives have mostly been used, especially in the synthesis of piromidic acid, pipemidic acid and their analogues, whilst in the tricyclic series the methylthio derivative (96) was reacted with hydrazine to give the versatile intermediate (97) (79JHC707). 

As with the purines, the replacement of chloro groups by amino groups has been one of the major building blocks of pyridopyrimidine chemistry, being employed in a great variety of reactions too numerous to catalogue fully, particularly in the piromidic and pipemidic acid fields. 

There are few examples of [5 + 1] cyclizations from pyrimidine intermediates. Two of these involve the chloropropionic ester (194), which gives the 5,6,7,8-tetrahydro-7-one (195) with ammonia (59JCS1849), and the cyclization of a 4-ethynylpyrimidine-5-carboxylate with ammonia to give a pyrido[4,3-. In a recent patent, 5-ethoxycarbonylpyrimidin-4-yl-j8 -alanine derivatives are cyclized with ammonia to pipemidic acid analogues (80GEP2903850). One-carbon pyrimidine [5 +1] syntheses are included in Section 2.15.5.5.1 above. 

Thermal cyclization of the arylaminomethylenemalonate afforded quinoline 3-carboxylate 630 whose reaction with 1,1-dibromoethane gave oxazolo[5,4,3-(/]quinoline 631. Acid hydrolysis and reaction with N-methylpiperazine gave 632 whose bactericidal activity is superior to that of pipemidic acid (82JAPK57203085) (Scheme 108). 

Amino-2-methy It hio pyrimidine Pipemidic acid Piromidic acid... 

Diethyl sodium phthalidomalonate Melphalan Diethyl sulfate Aminometradine Etidocaine HCI Fluorouracil Pipemidic acid Piprozolin Piromidic acid... 

Ethoxymethyleneethyl malonate Floctafenine Nalidixic acid Pipemidic acid Piromidic acid Rosoxacin... 

Eudragit RS microspheres containing chitosan hydrochloride were prepared by the solvent evaporation method using an acetone/liquid paraffin solvent system, and their properties were compared with Eudragit RS microspheres without chitosan. The content of pipemidic acid, an antibacterial, increased in larger microspheres as a consequence of cumulation of undissolved pipemidic acid particles in larger droplets. Pipemidic acid release was faster from microspheres with chitosan [212]. 

C2H5I 75-03-6) see Butibufen Cinoxacin Diethylstilbestrol Enoxacin Ethotoin Gallamine triethiodide Imiquimod Lomefloxacin Mosapride citrate Nalidixic acid Oxolinic acid Pefloxacin Pipemidic acid Tridihexethyl chloride Zaleplon... 

R= pyrrolidino Piromidic Acid R = piperazino, Pipemidic Acid... 

Pipemidic acid was prepared in 54% yield by the cyclization of /V-ethyl-N-(4-pyrimidinyl)aminomethylenemalonate (1046, R = pyrrolidino) on heating in polyphosphoric acid at 200-230°C for 10 min [73JAP(K)8800]. 

---