DE1670224A1 - Process for the preparation of triazolo-tetrazolo-pyridazine derivatives - Google Patents

Description

C. F. Boehringer * sons

GmbH Mannhe im

1468 a

Process for the preparation of triazolo-tetrazolo-pyridazine derivatives

(Addition to patent application B 89 5> 4 IVd / l2p) Subject of patent application B 89 524 ZVdAS .P let a

drive for the production of triazolo-tetrasolo-pyridazine derivatives of the formula I

CD,

in which X is a valence trio or a vinyl group " Y is an oxygen or sulfur atom and

R is a hydrogen or halogen atom, a lower alkyl, alkoxy, alkyl meroapto or amino group which is optionally substituted by lower alkyl or aoyl radicals is, mean «'. . ; '

characterized in that either ■ a). Hydrazones of the general formula II.

in which R, X and Y have the meaning given and Z is hydrogen or a nitro group « '··

. ', ..;. 1Ö0Ö09 / 21A-2:

treated with oxidizing agents or

b) CerbonaBurehydraiide of the general formula ZIX

in which R, X, Y and Z have the given · meaning, »·

possibly with the addition of a D «hydration * Bittele heated «or. . -

o) Amldraxone of the general formula IV .... ■

in which R, X, Y and Z have the meaning given to have" . . ■ '.

• e *

109809/2142 ■

optionally with the addition of an ammonia-binding agent heated, and in the event that Z denotes hydrogen, the substances obtained in a known manner nitrated, the substances in which R represents an amino group optionally substituted by lower alkyl or aoyl radicals, also subsequently .transferred into one another will.

In an embodiment of the process of patent application B 89 53k IVdA2 ρ, it has now been found that the compounds of the formula I - in the event that R does not represent a halogen atom - can also be prepared by reacting alkali metals with halides of the formula V '.' · ■ '

Shark

in which X, Y and Z have the meaning given above. Hai introduces a chlorine, bromine or iodine atom and

n * hydrogen or a lower alkyl, alkoxy, alkyl « mercapto or amino group, which is optionally substituted by lower alkyl or acyl radicals,

whereupon - in the event that Z is hydrogen - the held connections In per se known wsise afterwards nitrates tn »d the Subst & ssi ^ ni la dsnan a if necessary Aiiino group substituted by lower alkyl groups represents, naohtrKglloh converted into one another. <

. 109809 / 2H2. '

To carry out the method according to the invention, the ' Reaction components in suitable organic solvents (e.g. dimethyl sulfoxide * dioxane) or mixtures thereof heated with water. Any subsequent nitration or conversion of the radicals R which may be required takes place according to the methods described in the parent application.

The halides of the formula V used as starting products can, for example, by the process of the patent application B 8? 610 XVd / 12 ρ by cyclization of trofurfurylidene or nitrothienylidene-pyridazinyl-hydrazines or the corresponding amldrazone are obtained.

The method according to the invention is explained in more detail in the examples below «

109889 / 2U2

example

^ - (5-Nitro-2-furyl) -s-triazolo- [4 _J ^ -b] -tetrazolo-ri ^l _J 5 ^l -f1-pyridazine

Dissolve 0.52 g of 3- (5-nitro-2-fuxvl) -6-ohlor-s-trlazolo- [4,> b] -pyridazln (mp. 222-226 ⁰ C) in 16 ml of hot, 90 # igem, aqueous dimethyl sulfoxide, add 0.46 g of sodium and then 1 ml of 2N hydrochloric acid and allow to react for 2 hours at 100 °. After addition of another 0.25 g of sodium azide and 5 drops of 2N hydrochloric acid is again holding for 2 hours at 100 ⁰ C, allowed to cool and filtered off the Kristalllsat, which is washed thoroughly with water · yield: 0.44 g, mp 185th ° C (decomp.) * The substance can be recrystallized from dimethylformamide and from dioxane. According to the m spectrum, the 3- (5-nitro-2 «furyl) -s-triazolo- [4,3-b] r tetrazole- [1 ^! , 5'-Γ3-pyridazine in T & dtomorie-GloichgewiGht with an azido form [5- (5-nitro-2-furyl) -6-azido «e« triazolo- [4,3-b] -pyridazln] *

Example 2

3- (5-Nitro-2-furyl) -10-methyl-s-triazolo- [4,3 »b 1 -tetrazolori ^f » 5'-f] pyridazine

Dissolves 0.98 g of crude 3- (5-nitro-2-furyl) -6-chloro-7-methyl-s-triazolo [4,3-b] -pyridazine with a melting point of 126-129 ° (decomp.) In 14 ml of hot, 90% aqueous dimethyl sulfoxide, 1.75 2N hydrochloric acid and then 1.2 g of sodium azide are added and this is maintained at 100 ^° C. for 2 hours. After cooling, the crystals separated from the solution are filtered off with suction, Washed with 90% aqueous Dlmethylsulfoxyd, rub the filter residue with water, suction again (0.95 g) and crystallized from 15 ml 60% aqueous dioxane using activated charcoal. In this catfish one receives 0.63 g of> (5-nitro-2-furyl) -10-methyl-s- triazolo- [4,> b] -tetrazolo- [ ^l , 5'-f] -pyridaain in Form of yellow crystals

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of m.p. 165-173 ° C (decomp.). The ZR and HMR spectrum show that the connection in the tautomeric equilibrium is involved. an azido form [3- (5-nitro-2-furyl) -6-aaido-7- «ethyl-e-triaaolo- [4 _{J (} 3-b] -pyridazine].

The used as starting material · 3- (5-Nitro-2-furyl) -6-chloro-7 · methyl-s-triazolo- [4, j5-b] -pyridazine is obtained in the following way » keep:

3 * 17 g 3 "chlorine" -4-methyl-6-hydrazino-pyridazine (Pp. In 60 ml 73 £ aqueous methanol geioest warm and at 50 ⁰ C with stirring 3.68 g of 5-nitro-fur ^ offset on-2-ijnidccarbona säureäthyiester is kept 30 minutes 50 ⁰ C "drawn after cooling, the strong dark red colored crystals, washed with 75 £ aqueous methanol and obtains so ^ 9g of crude 6- ^[l N. - (5-Nitro-2-imidofuroyl} -hydrazino3-4-methyl-3-chloropyridazine of pp. 214-216 ° C (decomposition *) »3.9 g of this ^ substance are finely powdered and mixed with 52 ml of 5N- hydrochloric acid heated 6O minutes at 80 ⁰ C, the suspension is often thoroughly rubbed with a glass rod. After cooling, filtered off, washed with water and 3.2 g of crude 3- (5-Nltro-2 ~ furyl) -6 ~ 'chloro-7-methyl ~ s-triasolo- [4,3-b] -pyridazine of melting point 126-129 ° C. (decomp.) A sample of this (0.22 g) is made from 4 ml of a mixture of 2 ml of dimethylformamide + 2 ml of Dloxan + 1 ml of water recrystallized with the addition of activated charcoal and then melts at 136-139 ^O C (decomp) "

109809/2142

Claims (1)

Claim Process for the preparation of Triasole-tetraBolo-pyridaxine derivatives of the general formula X ¹ in <isr X a Vmlerizstrloh or «ine Y «in oxygen» or sulfur atom and R ^{1 is} hydrogen or a "lower Allqrl-" alkoxy, Alky, mercapto or amino groups, if appropriate substituted by lower alkyl or Aeylreete is "mean" äadureh marked * öai san in ÄuegQsfc & lfeung #as Verfahrene der H & upt & nßftXdung B 89 5 ^ ΤΨύ / 12 ρ LUßkU & zlut. with the formula V ifeliJher X, Y uM R ¹ just stated Ifel a chlorine brandy Jodatc " unft converts, whereupon - in the event that Z is hydrogen the compounds obtained are subsequently nitrated in catfish known per se and the substances "in which R represents an amino group optionally substituted by lower alkyl or aoyl groups" are subsequently converted into one another. 109809/2142