Piperazin-2-ones preparation

Stage 4 Preparation of 1-l2-Phenyi-2-Methoxyl -Ethyi-4-[3-Phenyl-3-Hydroxypropyl] -Piperazine Dihydrochioride - In a double-neck flask equipped with a thermometer and a mechanical stirrer, there is placed in suspension in 800 ml of methanol, 233 grams of 1-[2-phenyl-2-methoxy]-ethyl-4-[2-benzoyl-ethyl]-piperazine dihydrochioride (0.55 mol). It is cooled to approximately 5°C, and 46 grams of NaOH pellets dissolved in 80 ml of HjO are added. When the temperature is about 5°C, one addition of 29,2 grams of sodium borohydride in 40 ml HjO is made. The ice-bath is then removed and stirring continued at ambient temperature for 6 hours. 

The presence of a rather more complex substituent on the remote piperazine nitrogen atom is consistent with tranquilizing activity. The preparation of one such agent, 16, begins with reaction of thioxanthone 11 (obtained by a sequence analogous to that used to... 

Amino-2-methoxyphenyl)perhydropyrido[l,2-tf]pyrazine was prepared from a 2-(5-nitro-2-methoxyphenyl)-3-one derivative by catalytic hydrogenation over Pd/C catalyst, followed by the reduction of the 3-oxo group by treatment with BH3-THF complex <1999WO99/042465>. A nitro group was reduced to an amino group in 2-[4-(3-nitrophenyl)piperazin-l-yl]butyl]perhydropyrido[l,2-tf]pyrazine-l,4-dione <2001JME186>, in 8-hydroxy-... 

In addition to the ionic liquid-mediated procedure in solution (see Scheme 6.112), Leadbeater and coworkers also presented a solid-phase protocol for a one-pot Mannich reaction employing the above mentioned chlorotrityl linker [67]. In this approach, p-chlorobenzaldehyde and phenylacetylene were condensed with readily prepared immobilized piperazines (Scheme 7.56). 

Although the formation of symmetric piperazine-2,5-diones is a well documented transformation (93AHC187), the unsymmetric -ones have been prepared from AAs or their amides with acyl halides, such as pyruvoyl chloride (81RTC73) and a-bromopropionyl bromide (91H923). 

The usefulness of piperazine and its derivatives for the preparation of polyamides has been known for some time, and it is one of the few disecondary diamines which can be employed to prepare high-melting polycondensates. Piperazine polyamides are especially useful as hot melt adhesives (68USP3377303), since they display unusually good adhesion to vinyl-based polymers such as poly(vinyl chloride). Piperazine is also the preferred diamine for the preparation of thermoplastic polyamides which exhibit the combined properties of low melt viscosity, high softening point and impact resistance at low temperatures (80USP4218351). 

Pyrazino[l, 2-a Jpyrimidines can also be prepared from piperazin-2-ones. Catalytic hydrogenation of 4-benzyl-l-(2-cyanoethyl)piperazin-2-one (279) over Raney nickel gives the cyclized product (280) in near quantitative yield. The cyanoethyl piperazine can be prepared from the corresponding piperazine (278) by reaction with acrylonitrile (73BCJ3612). 

There is the 3 methods for preparing of 8-azaspiro(4.5)decane-7,9-dione, 8-(4-(4-(2-pyrimidinyl)-l-piperazinyl)butyl) monohydrochloride (U.S. Patent 3,717,634). One of them is follows a mixture of 0.1 mole of the substituted glutaric anhydride, 0.1 mole of l-(4-aminobutyl)-4-(2-pyrimidinyl)piperazine (U.S. Pat. 3,398151), and 300 ml of pyridine was refluxed until imide formation was completed. The degree of reaction was readily followed by taking an aliquot portion of the reaction mixture, removing the solvent, and obtaining the infrared absorption spectrum of the residue. When reaction is complete, the spectrum exhibited typical infrared imide bands at 1701 and 1710 cm-1 whereas if incomplete, the infrared spectrum contains amide and carboxyl absorption bands at 1680, 1760 and 3300 cm 1. 

Inspired by the bioorganometallic approach, two series of ferrocenyl pyrrolo[ 1,2-a] quinoxalines were designed and prepared (Fig. 17). The derivatives were tested in vitro against three different strains of P. falciparum F32, FcBl, and PFB [107]. The best results (IC50 between 30 and 70 nM in comparison to CQ IC5o = 225 nM) were observed in the first series with a bis(3-aminopropyl)piperazine as a linker. These compounds were tested for then ability to inhibit p-hematin formation. For all but one case, the derivatives did not interfere with hemozoin formation... 

Benzylperhydropyrido[l,2-a]pyrazin-6-one was prepared through the cyclization of 287, obtained from 285 via 286 (93JOC690). From the reaction mixture of 2,3-di(2-tetrahydrofuryl)piperazine, treated with HBr gas in AcOH at 90-95°C, then with KOH, l-(2-tetrahydrofuryl)-9-hydroxy-perhydropyrido[l,2-a]pyrazine could be isolated (61BSF2135). Cyclization of 2-(l,2,3,4-tetrahydroxylbutyl)quinoxalines in an acidic media gave 8H-pyrido[l,2-a]quinoxalin-8-ones together with a small amount of their 9-... 

Arylpiperazines can be prepared in a one-pot procedure by ipso SNAr of piperazine derivatives with //6-fluoroarene complexes la, 33a,b,d. Indeed, piperazine derivatives react with fluorobenzene derivatives in DMSO in the presence of K2CO3 at 80 °C to give, after 2.5 h, complexes 3m and 3k (Nu = piperazine) in good yields (Scheme 18) [34]. Piperazine itself may be used as a nucleophile and gives the monoarylpiperazine derivative uncontaminated by any symmetrical N,N -bis(aryl)piperazine, allowing the direct preparation of unprotected compounds. 

Preparation of crude l,l - [(bisethane-l,fV-diyl)piperazine]dioxy bis[(llaS)-7-methoxy-l,2,3,lla-tetrahydro-5H-pyrrolo[2,l-c][l,4]benzodiazepin-5-one]... 

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