39715-02-1 Usage
Originator
Miretilan,Sandoz,Switz.,1981
Uses
[endralazine].
Antihypertensive.
Manufacturing Process
(a) 6-Carbethoxy-5,6,7,8-tetrahydro-3(2H)pyrido[4,3-c]pyridazinone:
Produced from 450.5 g of 2,3,4,4a,5,6,7,8-octahydro-3-oxo-6-
pyrido[4,3c]pyridazinecarboxylic acid ethyl ester and 320 g of bromine. The
bromine is added dropwise to a boiling solution of the ester in 200 cc of
chloroform over one hour and the mixture is stirred for another hour at the
same temperature. 1 kg of ice water is added to the mixture, the chloroform
portion is separated, and the acid aqueous phase is again extracted with 500
cc of chloroform. The semicrystalline crude product obtained after
concentrating the chloroform phase, is recrystallized with 250 cc of absolute
ethanol, melting point 165°C to 168°C (decomp.).A solution of 223.2 g of 6-carbethoxy-5,6,7,8-tetrahydro-3(2H)pyrido[4,3-
c]pyridazinone in 1 liter of concentrated hydrochloric acid is heated to the boil
at reflux for 22 hours while stirring. The mixture is concentrated in a vacuum,
and the resulting crude crystalline hydrochloride of 5,6,7,8-tetrahydro-
3(2H)pyrido[4,3-c]pyridazinone, having a melting point of 307°C to 310°C
(decomposed from methanol), is suspended in 0.75 liter of methanol, and 0.4
liter of triethylamine is slowly added to the suspension. After stirring for 15
minutes and cooling the violet suspension, the crude base is obtained. 25 g of
the crude base are recrystallized from 300 cc of methanol, mixed with 10 cc
of concentrated ammonia and 40 cc of water, with the addition of a small
amount of coal. 5,6,7,8-Tetrahydro-3(2H)pyrido[4,3-c]pyridazinone has a
melting point of 223°C to 225°C (decomp.).(b) 3-Chloro-5,6,7,8-tethydropyrido[4,3-c]pyridazine: Produced from 30.3 g of
5,6,7,8-tetrahydro3(2H)pyrido[4,3-c]pyridazinone suspended in 250 cc of
phosphorus oxychloride. The suspension is heated to the boil while stirring.
The resulting solution is stirred for 1 hour at the boil and then concentrated to
an oil in a vacuum. 150 cc of ice water and 40 cc of concentrated ammonia
solution are added to this oil, and the mixture is extracted twice with a total
of 300 cc of chloroform. The chloroform phase is concentrated in a vacuum.(c) The crude unstable base is converted into the maleate for working up. This
is effected by boiling 24.8 g of the base in 150 cc of methanol with 17.5 g ofmaleic acid. Upon cooling the solution, the crude maleate is obtained, which is
recrystallized from methanol with the addition of a small amount of coal. 3-
Chloro-5,6,7,8-tetrahydropyrido[4,3-c]pyridazine maleate has a melting point
of 162°C to 164°C (decomp.).A mixture of 12.6 g of benzoyl chloride in 100 cc of ethylene chloride is added
dropwise to a suspension of 25.6 g of 3-chloro-5,6,7,8-tetrahydropyrido[4,3-
c]pyridazine maleate in 250 cc of ethylene chloride and 21.8 g of
triethylamine within 18 minutes at room temperature while stirring. The
mixture is stirred at room temperature for a further 14 hours, 200 cc of water
are added, the organic phase is separated and concentrated to an oil in a
vacuum. Upon adding ether/dimethoxyethane to this oil, crude 6-benzoyl-3-
chloro-5,6,7,8-tetrahydropyrido[4,3-c]pyridazine is obtained. After
recrystallization from absolute ethanol with the addition of a small amount of
coal, the compound has a melting point of 125°C to 127°C (decomp.).
Displacement of the halogen with hydrazine leads to the formation of
endralazine.
Brand name
Migranal (Novartis).
Check Digit Verification of cas no
The CAS Registry Mumber 39715-02-1 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 3,9,7,1 and 5 respectively; the second part has 2 digits, 0 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 39715-02:
(7*3)+(6*9)+(5*7)+(4*1)+(3*5)+(2*0)+(1*2)=131
131 % 10 = 1
So 39715-02-1 is a valid CAS Registry Number.
InChI:InChI=1/C14H15N5O/c15-16-13-8-11-9-19(7-6-12(11)17-18-13)14(20)10-4-2-1-3-5-10/h1-5,8H,6-7,9,15H2,(H,16,18)
39715-02-1Relevant articles and documents
3-Hydrazino-cycloalkyl[c]pyridazines
-
, (2008/06/13)
This invention provides aminopyridazine derivatives of formula I, SPC1 wherein R1 is amino, or an EQU1 group, wherein each of R3 and R4 is alkyl of 1 to 4 carbon atoms, or R3 and R4 together with the carbon atom to which they are bound, form a cycloalkylidene radical of 5 to 12 carbon atoms, R2 is hydrogen or methyl, A is a --(CH2)n -- group, Wherein n is 0 or an integer from 1 to 7, or an >N--CO--R5 group, Wherein R5 is alkyl or alkenyl of 1 to 16 carbon atoms, cycloalkyl of 3 to 8 carbon atoms, 1-adamantyl, or a --(CH2)m --R6 group, Wherein m is 0 or an integer from 1 to 4, and R6 is phenyl; phenyl monosubstituted by fluorine, chlorine, bromine, alkyl or alkoxy of 1 to 4 carbon atoms, alkylmercapto of 1 to 4 carbon atoms, or phenyl; phenyl substituted by two or three substituents of the group chlorine, alkyl or alkoxy of 1 to 4 carbon atoms; diphenylmethyl, the phenyl rings of which may be monosubstituted by fluorine, chlorine, bromine, alkyl or alkoxy of 1 to 4 carbon atoms; or naphthyl, Or an --OR7 group, Wherein R7 is alkyl or alkenyl of 1 to 4 carbon atoms, or phenyl, phenylalkyl or phenylalkenyl which may be monosubstituted on the phenyl ring by chlorine, alkyl or alkoxy of 1 to 4 carbon atoms, and in which the alkylene or alkenylene chain is of 1 to 4 carbon atoms, And R8 and R9 are each hydrogen or alkyl of 1 to 4 carbon atoms, And acid addition salts thereof. The invention also provides processes for the production of said compounds. Said compounds and pharmaceutically acceptable acid addition salts thereof are useful as antihypertensive agents.
