DEP0036768DA - Process for the preparation of piperazine-1-carboxamides - Google Patents

Description

Asrarioan Gy & na & id Company
ρ 36 768 ITc / 12 p D

American Ayanaid Company
30 Bockefeiler Ilaaa ₉ Hew Iork ₉ Iiew York, V.3t. “.

Meue description.

Tgrfahrea _ii Sar _i äerstclluag, from PiperaMn-l-carboxylic acid-

Etisats au Tateat - (patent application ρ 24 625 IVc /, 2p)

The present invention relates to the production of Pipex% azine-1-carboxamides and their Balogeawaseer substance salts and represents a better or more frequent modification of the Krfinduag. i-atent ——— (patent application Mr. ρ 24 625 IVc / 12p).

G-eg & etaad tee Patents - —— - (i- at en t azuse 1 dung ρ 24 625

i ¥ c / 12p) ajiter is another ice process for the production of Mper ajsin-i-e ^ rboaeaureaaidfm from the general Poriaeli

Alc.

In the J> * fiber or an Al / .yl group aa # Alk · mean an alkyl group. These compounds are highly effective in the treatment of filariasis and in veterinary practice in the treatment of iscurides in Iieren _for 2nd day . Dogs. They have a small aität Vorf- and are RATIOS i amäfiig low roeeii safer Äirk.öuiE.

On the basis of the present invention, a method was worked out "? Ip © raeia-1-earfconsüureaisdäe {-and Inre hydrogen halide salts; rait the general Sormeli

Uk. JJJu

nielli ß ^y In —Κ

in which hydrogen or a low molecular weight alkyl group and Jlk denote a low molecular weight alkyl group. The TerfaIari ^s H beetott in the acylating of an alkyl-substituted ^ iperasias of the formula:

Alc ₉

I-B

in which M Tiatl Alk "has the meaning given Iia ¹ Hen _si with a Carba®y Ihalogeata, the a" nitrogen atom is substituted by, ice or e "d Alltylgrappea, in order to a hydrogen halide" alz "Γη and in the alkali haadlong of the llalogeawasserBtoffsalaes for the purpose of producing I iperazine-1-carboxamides. Under the, uacruck "niedrlgJöolekulare alkyl group ^w here is group Jiit ei" to four Xo ^ lenstoffatoiEen to understand a 4lkyl.

! - ■ The yerbiadutagea of this cfiaduag are allgeseiae »highly effective against pilaricides The alkylplperazine-1-carboxamides are colorless Ms setefeachgellie Jle, which are soluble in most organic solvents. X in the form of their hydrogen halide salts are they white, ia ftaeser) U5aliche, hygroscopic cal se *

"In the method of the Brochfiiarung Erfiaduiig can Attsgangsmstterial as C-substituted © AlkylpIperaeine, for example 1,2, 3 ~ I 'rii3ethylpiperazin; 2,5-Iimet bylpi piperazin j in 1, 2, 6-'Iriaiethylpiper &sin; 2,6- rimethylpiperazine or 1,3,5-irimethylpiperaaln etc. can be used, either in waeeerfreler? orm or al® hydrate, e.g. 2 , i > -i ) imethy ipiperazine hexahydrate. non-aqueous solvents such as benzene, loluol, chloroform, Ietrachlorkohlea- 3t off, Oibutylather and used ähnliehe. 3s is more advantageous to a "lkylpiperazin as a hydrate thereof to operate as -.uegangsmaterial and sufficient .Uberschuß thereof for

Maduag of the hydrogen halide produced during the reaction.

The action is carried out as a solution. J? Emperaturen ^ö siaä usually auereiohend of 20 ° Iiis 100 to the Umeetsung la to complete an average Zeltrauua. In general, work is carried out at 30 ° to 50 ° if aqueous alcohol is used as the solvent , while slightly higher temperatures are desirable for anhydrous solvent. Bsi temperatures below this level precedes the reaction is too slow and temperatures over the ten no particular advantage.

In the main, "any carbamy! Halides from Porrael:

Uk.

^{, k} ^^^^ - SeOX are used, in which all »and. ü the

Above mentioned bedeatuag own ami X is halogen? So g! B "Ltonomethyl, lionoethyl, laonopropyl, dimethyl, piethyl, biisopropyl, Γ-in-propyl, diethyl ether earbamyl halides and the like. Representations using diethylene acid halide, such as oloride, may be given as illustrative examples, since their chemical watering is typical. While a can be any halogen, chlorides and bromides are most useful.

If the reaction takes place in an aqueous alcohol such as ethyl alcohol, it is not

AlKylpiperazlnnnnnnnnnnn after the action ämrcfc imsäuera with an acid such as hydrochloric acid, precipitated. It is removed by filtration, and the main thing that remains is the alkylpiperazine-1-carboxamide and 1,4-dicarboxamide in the aqueous alcohol-? I! entered, rlonaentrieren by distillation and then azeotropic he te stillst ion sit Beaisol _i Soluol uev ;. 2 "eck8 removal of the last traces of acid leave the alkyIplperaai / i * 1-carbonic acidic) 3:, yla ide% ie their insoluble hydrochlorides in suspended" 2usband, "while the acylpiperazine-1,4-carboxamides in solution blefbsa * Me ei steres -die then obtained in the form of their salts in ia & t pure state by filtering off. The latter clone aas of the filtrate by conseating with the help of distillation, ibdaapfea or Sühlen ssurgewoanea »

if the isolated product is an alkylpiperazine-1-carboxylic acid lajßid with unsubstituted 4-position, a further

re alkylation ait üilf © four for sis eekun & üren .Aaine ge brau eb * IieivQB Aliiyli-oruHgiiaiotliodea VorgenociBi ·.: · » be. In general hXIq ulkylsulffcte, i.lkylsulionfatö and ^ Ikylbalogeniö © used as Alkylienirigsiiilttöl TioriIeB ₉ si: glichst except exerts AIfcyljotfide, -ßa. To form 4t © se ä & m Seigan _f qu & teraare salts * In speaiellen FKII the Letaylierung provides "3ie reducing ^ etaylierung - improving ways as oils above Λ Ilcyllerungsisittel *" a vorsügiicne s $ etiiOde using ZforaisKIenyd .in formic acid or For "sk-.ldeaya la hydrochloric acid in the case of Xinfec-tsub *

The process of the present jury charge is explained by never following examples.

£ ₉ S-JDiaffi tMy lt> i ja erazin ^ l ^ c ^ r boa säuracl t a. t byl eel there

Iis 400 Toilea dry benzene wcröon 114 parts anhydrous 2 , 5 -JDisietliylpl |>er5; 2in dissolved at 65 °. * Paaa vreröen mmter .Sislialtuag -silier Teatp ercastar from 65 ° to? 0 ° tropfenveiae 6?, 8 parts Eittliyl * oarbamylcfüiae added * Tie Iieuktionsaiecaung is' / 2 * Stae long b "l? ϋ ° · gerünrt and FCSA st-d under Eüekflucg 6th Very heated rie Xi € 'SditiOrt © .sii®eöusg «lrd a.uf 15 ° - 20 ° e.bgekablt, 120 parts of AtaylaX-kohel are added tmü the Miaefaung ai-rd durca given by Icon · centered Salzsraare & ngesdaert * See aient uagesetzte 2.5 SimetbyX-plperasin falls as riiiydrooalo user_rid sozs and is Durea filtration removed * Sas JFiltrct Kird to au eirap & BEARDED iloneistena "singedielt * - ΰΙ®Β®τ Euekstasd is cooled old 50 '5i & he SstvmlmgB strong base cßcfe ^ üciit and the si eil separating « CI la rdäthyliktaer dissolved season, the ethereal listing over» solid Ialiu & hy drosy d dried and then JJUößun ^ eaittel removed by distillers, the jsüefcsfäiiü is distilled under veralndertea iraak 2,5-ri ^ ri : 2iln -1-earbonßäurediötliylajBid sit a boiling point of 105 ° * 107 ° - at 1.5 nm

BelepieX 2.

2yfU5- '£ i * i ^

91 parts 2,5-I; iüaethyl | jiperiiZin - ^ - oarbon ^ äurediäthyliHäiä wer * -

Claims (1)

the la 65 parts 90 f? i £ © r ^ aeiseasSare solved * Baaa «earth WSJirea ^a 13 Kiaut m 53 ■ ieile 36> iger t & aeorifcer IOraeidehyd at ? 5 ° ttfop- Sa ^ egebea ", 7;! e Iiseaun ₁ ^ is 2 Staadea long at 105 ° to 110 ° at the edge of the river. The excess acidic acid is removed from the furea I ^ stillutioa, 'bia the teaperiir des Eue & sfcende. iiUt etea 150 ° risen i? t .. "Ji & .en Abdestillieron der 2mei" ens & are will ösr üliok & iimü. cooled to 25 ° * Br tsird with 50 Filger Watroalaug © g-egea tfaonolphtsleia strong aXkaiisscfe · made IIAS look from * »acaetdea & D is oil-insulated and ti © he Kalia ^ iydroacydperleii getreeka © * · ilixck AEEA drying ■ If ös.s oil under Tensiafiertea JJ ⁱ Tucfc de-η ti Iii »art imä results in relais 2 , 4 ₃ S-JTiraet Ip ipor & ain-l« earfeoaoöö- redläthylaaiii with eiaea boiling point to 86 ° Ms 89 ° at 1.0 as * 1 * ancestors aar manufacture- tob .Fipsstisia-l-cirrfeoasiiaresiaiten (liad their HalQgeawi? * Sss »first © IT sslaen) iron der srHgomeiaoa .Formels la der «t-afeserßtoif or eima aiedrigfflOlekul & r * e AXfcylipyappe mad l -. 'lk» © ine aiodrigBQlökulare iilfcylgrupp © "mean aaea Pateat --— . {i * atentnasielduag ρ 24 625 I? c / 12 p), thereby gekenet .-- sr.is ciii ^ lcuDstitaierter j ^ iperazia mn the ForaeXs • A3 * ,. R ■ or cleGösa iiydr & t alt eiaeci Qsrbamylhalogaaifi _s üU-a sa sticket oft'— atom or eiae © tier zvel i-.lkyl> ru? pan is appropriately substituted in Oa ^ emrt ei »-se Losuaifeaittels _t special« ^ ssrigem alcohol preferably with - 100 ° acy lie - 1 becomes, then it arises Hydrogen halide st-lr, la ίίbücher ', Ieise with the help of i JLkaliea in d' / S free l'ipo. szia-l »deinstalledC« re & erli fiöarfUart ^ ird · 2a ¹ ZerffefereB iiccii claim tin.öurca .g-ekeanzeichaot that at fe-remntoiif. of an El ^ yleubstituierten Piperazia & ydr & ts Rieses in the c oil che «Übersotiuso used v.irö that the during the HeaktJLeta eatsteäeßöe Jalogenv, · .-» se ■ stoff becomes gobuadea. J * Ibaaderwng der Verf-liyea nach äea Ancpriicfcea 1 «ad 2, because ITBkeaazsioftBnyt _i eLis .se nel Venfeaduag a la <t-position not e: dated. ! pertussins c1 β j.us ^ ;. agoiaat cri al örs according to cor .Kcyliorun ^ with the ΰ arbsraylh.-logoniö resulting pipcrazine-1-carboxylic acid: .mid .by Β ^ ΛηΐΆηη ^ a with an alkylation aittsl Bio, ^ deeply alkylated further is and Iiieflsei © isia tethyliorung ^ «» ecitm ^ ssifr by reducingi ^ reade methyl ierun ^ r using tob, iOriiutldchyd? i ι · θ ·