DE2232038A1 - 3-AMINO-1H-PYRAZOLO SQUARE CLAMP ON 3.4-ANGLE BRACKET FOR PYRIDINE, THEIR PRODUCTION AND USE - Google Patents

Description

FARBWERKE HOECHST AG formerly Master Lucius & Brüning

File number: - HOE 72 / F

Date: June 28, 1972 Dr Ot / cv

3 ~ Ainino-1H ~ pyrazolo [3,4-b] pyridines, their preparation and Use"

The present invention "relates to new 3-amino ~ 1H-.pyrazolo- [3,4-blpyridines of formula I.

■ ζ. '

wherein X is a primary, secondary or tertiary amino group, a hydrazino, a hydroxylamino, an ether or TMo- ' ether group,! hydrogen, an optionally substituted. th is alkyl, cycloalkyl, aryl or heterocyclic radical and Z is hydrogen or an alkyl radical.

The new compounds can be obtained in the manner that a 2,6-dihalo-3-cyanopyridine of the formula II

■. Y

J- ^, CN

f J ' (ID

Hal .- \ ^AHal ■

wherein T has the meaning indicated above and Hal represents a chlorine or bromine atom, is reacted with ammonia, a primary or secondary en amine, a hydrazine, a hydroxylamine, a hydroxy oderMerkaptoverbiridung and the compound of formula III thus obtained

- 2 ~ 309882/1355

CN (III)

Hal

where X, T and Hal have the meaning given above, with a hydrazine of the formula IV

j '■. Z-NHKH ₂ (I?). ■

condensed.

The reaction of compounds of formula II with the amines, hydrazines, hydroxylamine en, hydroxy or mercapto is carried out at about 20 bis'100 C, preferably at about 60 to 80 C ₁ advantageously in an inert solvent, for example a lower aliphatic alcohol with 1 up to 4 carbon atoms. If appropriate, the reaction can also take place in an excess of the amine, hydrazine or hydroxylamine or the hydroxy or mercapto compound as solvent. The exchange of the halogen atom in the 6-position is confirmed by analyzing the NMR recording of the compounds of the formula III.

The condensation of the compounds of formula III with hydrazine is conducted at about 70 to 150 ⁰ C, preferably at about 100 to 13O ⁰ C _y in an aqueous or aqueous-alcoholic medium.

The preparation of the new compounds can - starting from the compounds of the formula II - in a two-stage process or in a so-called one-pot process.

309882 / 13SS

The compounds of the formula I according to the invention can possibly also in their tauto-internal formulas, for example as compounds of the formulas V, VI or VII

Λ.Λ- "^ NZ (V) V - \ _T A _tttt ^ _N _z

Jv JN Jji

XNN "

NH. (VII)

where X, Y and Z have the meanings given, are present.

The 2,6 ~ dihalo ~ 3-cyanopyridines used as starting compounds of the formula II can be obtained by known methods, for example by reacting the appropriate 2,6-dihydroxy-3-cyanopyridines with halogenating agents, such as phosphorus oxychloride, phosphorus pentachloride or phosphorus bromide (See J, org. Chem. 2J ?, 560/1960) or by implementing the corresponding 1-alkyl-2-hydroxy-6-pyridones with halogenating agents (cf. German Offenlegungsschrift 2 04-9 831).

As starting compounds of the formula Ι.Γ come, for example 2,6-dichloro- or 2,6-dibromo-3-cyanopyridines are considered, which in 4-position an optionally substituted alkyl group, for example a methyl, ethyl, propyl, butyl, hexyl, 2-dialkyiamino-ethyl, 2-morpholinoethyl, 2-aryloxyethyl, 3-alkoxypropyl, benzyl or pyridylmethyl group, or one optionally substituted aryl radical, for example a phenyl, halophenyl, alkylphenyl or alkoxyphenyl radical, a cycloalkyl radical, for example a cyclohexyl radical, or a heterocyclic radical, for example a pyridyl, thiazolyl or FuryI radical. The primary and secondary amines are aliphatic, cycloaliphatic, araliphatic, aromatic and heterocyclic amines into consideration. Suitable primary amines are, for example:

309882 / 13SS - 4 ~

Ammonia, methylamine, ethylamine, 2-hydroxy ~ ethylamine, 2-methoxyethylamine, 3 ~ phenoxyethylamine, n ~ and iso-propylamine, 3-hydroxy-, 3-methoxy ~ and 3-iso-propoxy ~ propylamine, 3 ~ cyanopropylamine , Allylamine, 1- or 2-methallylamine, n-, iso ~, sec- and tert-butylamine, 2 ~ amino-2 ~ methylpropanol- (1), crotylamine, 3-amino ~ pentane, n- and iso-amylamine, aniline, methyl and. Methoxyaniline, dimethylaniline, amino-naphthalenes, N, N-dietbylethylenediamine, NN-dimethyl- or NN-diethylpropylenediamine- (1.3). As secondary amines, for example, dimethylamine, diethylamine, K- (2-cyano-ethyl) -K- (2-hydroxy-ethyl) -amine, K-di- (2-hydroxy-ethyl) -amine, N-di- (2-cyano-ethyl) -amine, N-methyl-, N ~ iso-propyl-, Nn-butyl-, N-cyclohexyl- and II-benzyl- (2-hydroxyethyl) -amine, di-η- and di iso-propylamine, di ~ n- and di-iso-butylamine, di-n-amyl, and di-n-Hexj ^r lamin, morpholine, pyrrolidine, piperidine, N-methyl-piperazine, N-methyl and N- Ethyl-cyclohexylamine, N-methyl-benzylamine, N-methyl-3-methyl-benzylamine, K-Hethj ^ l N-ethyl, N-2-hydroxy-ethyl and N-benzyl-aniline, N-methyl and N-ethyl-2-chloro-aniline into consideration.

Examples of suitable hydrazines are ": N-Methy 1-N", N-hydrazine, N.N-dimethylhydrazine, N.N-diethylhydrazine, phenylhydrazine, N-methyl-N-phenyl-hydrazine, N-amino-pyrrolidine, I \ VAniino piperidine, N-amino-piperazine and N-amino-morpholine.

Examples of hydroxylamine compounds include hydroxylamine, Hydro: ylamine methyl, ethyl, propyl or butyl ethers and their N-alkyl derivatives into consideration.

The hydroxyl or mercapto compounds are aliphatic, ar-ali phatic, cycloaliphatic, aromatic and heterocyclic compounds, for example aliphatic alcohols with 1-8 Carbon atoms, alkylene glycols and their ethers, cyclohexanols, Phenylalkyl alcohols, phenols, dioxybenzenes and their monoethers, Naphthols, aliphatic mercaptans, thiophenols and heterocyclic oxy compounds into consideration.

309882 / 13SS

The hydrazines of the formula IV are hydrazine and monoalkylhydrazines, like N-methyl-, N-ethyl-, or N-propy! hydrazine in Consideration. "

The compounds according to the invention are valuable intermediates for the production of dyes, especially azo dyes of the formula VIII

(VIII)

where Z _{1 is} an optionally substituted alkyl or aralkyl radical, K is the radical of a coupling component and A is an anion and X, Y and Z have the same meaning as in formula I. These dyes, which are particularly suitable for dyeing polyacrylonitrile, are very strong in color and generally show good fastness properties. The following examples serve to illustrate the invention.

309882 / 13SS

Example l,!. ", L

93 * 5 parts by weight of 2,6-dichloro-3-cyano-4-ynethylpyricine heated to boiling in 300 parts by volume of ethanol and within 80 parts by weight of diethylamine are added for one hour. Man holds two hours at boiling temperature, the solution cools down, sucks; the colorless crystalline precipitate, washes it well Water and converts the moist product into a 500 volume part full flask. After adding 150 parts by weight Glycol and 50 parts by weight of hydrazine hydrate (80%) are heated 3 hours under reflux. It is then cooled, parts by weight of ice water are added and the crystalline precipitate is sucked off away. The compound is obtained in an almost quantitative yield the formula

which is purified by recrystallization from isopropanol. Analysis: C ₁₁ II ₁₇ N ₅ calc. : 31.9% N Found: 31.5% N

• - 6 -

30S832 / 13S5

Example 2 ^V

93.5 parts by weight of 2,6 ~ dichloro ~ 3-cyano-4-met.hyl ~ pyridine are dissolved in 400 parts by weight of methanol and then mixed with 27 parts by weight of sodium methylate in 200 parts by weight of methanol that the temperature does not exceed 50 ⁰ C. After the addition has ended, the mixture is stirred for 6 hours at 50 ^° C., cooled, the solution is treated with ice water and the precipitate is filtered off with suction. The moist product is dissolved in 150 parts by weight of ethylene glycol, 50 parts by weight of hydrazine hydrate (80%) are added and the mixture is heated to the boil for 3 hours. The mixture is then cooled, ice water is added to the mixture, the crystalline precipitate is filtered off with suction, washed well with water and dried. The compound of the formula is obtained in high yield

which can be recrystallized from alcohol.

Analysis: C ₈ H ₁₀ N ₄ O Calc .: 31.5% N Found: 31.3% N

example ⁷ y :

37.4 parts by weight of 2,6-dichloro-3-cyano-4-methyl-pyridine v / earth in a mixture of 100 parts by weight of ethylene glycol and 120 parts by weight of hydrazine hydrate (80%) to boiling for 2 hours heated. Then let it cool down, add 100 parts by weight of ice water to the mixture and suction it off. You get in high yield the compound of formula.

H ₂ N. HK

Analysis: C ₇ H ₁₀ N ₆ · Calc .: 4-7.2% N found

- 7 309882 / 13SS

- t ■ "

Example 4:

37.4 parts by weight of 2,6-dichloro-3-cyano-4-methyl-pyridine in 100 parts by weight of ethanol within 30 minutes 45 parts by weight of 3 ~ N., N ~ dimethylaminopropylamine added and Heated to the boil for 3 hours. It is then cooled, mixed with ice water and decanted from the precipitated oil. the oily phase is absorbed in 100 parts by weight of ethylene glycol and mixed with 50 parts by weight of hydrazine hydrate. One heats up 3 hours under reflux, cools, dilutes the mixture with Ice water and the viscous crystalline mass is distilled in a vacuum. The compound of the formula is obtained in high yield

Analysis .: C ₁₂ H ₂₀ N ₆ Calcd .: 33.9% N Found: 33.7% N

Example J? __: _

37.4 parts by weight of 2,6-dichloro-3-cyano-4-methyl-pyridine are dissolved in 200 parts by weight of methanol and a solution of 18 parts by weight of n-butyliaerkaptan and 10.8 parts by weight of sodium ethylate in 100 parts by weight of methanol are added so that the Temperature does not exceed ^{40 ° C.} The mixture is stirred for 3 hours at this temperature, the mixture is poured into ice water and decanted from the separated oil. The oily phase is heated to boiling in 100 parts by weight of ethylene glycol and 30 parts by weight of hydrazine hydrate for 1 hour. It is cooled, the solution is poured into ice water, the precipitate which has separated out is filtered off with suction and dried. The compound of the formula is obtained in an almost quantitative yield

Analysis; C ₁₁ H ₁₆ N ₄ S Calc .: 23.7% N Found: 23.7% N

309882/1355

- 8 "■

Example]. 6:

37,4- weight of 2,6 ~ dichloro-3-cyano ~ 4 ~ methyl-pyridine are heated for 12 hours at 100 ⁰ G in the autoclave in 200 parts by weight of alcohol and 20 parts by weight of methylamine. The mixture is stirred in ice water, the precipitate which has separated out is filtered off with suction, washed well with water and heated to boiling with 100 parts by weight of hydrazine hydrate for 2 hours. It is then cooled, diluted with water and ¹ ... the crystalline, colorless precipitate is filtered off with suction. The compound of the formula

CH,

CEL-NH
3

can be purified by recrystallization from isopropanol.

Analysis:

Calc .: 39.5% N Found: 39.1% N

The table below contains further * according to the invention Connections of PormeI I:,

ζ Summation formula • " At·. H O ₇ H ₉ N ₅ «, 9 ' H O ₁₃ H ₁₇ H ₅ 28.2 H C ₉ H ₀ H ₅ 36.7 ■ H 34.1 H C _n H ₁₇ Sf ₅ 32.0 H C ₁₃ H ₁₉ H ₅ 28.6

-NH.

-NHC ₆ H ₉

-NHC ₂ H
3

-HHC ₇
-NH J / r

CH,

CH,

CiL

CH,

CH-

CH,

- 9-

309882/1355

• X

-NH-CH

2 "VJ

-NH-CH

-NH

OCH-

-NH

-O

-IH -NHC _x H ₀ (iso)

₅ H ₇

-NH-

> CH ₇

.NH-CH ₂ -CH ₂ -OH

-NHCH-CH-N '

^CH 3.

| Y_ 1 Z CH _x H CH ₃ H CH _x
3 H 3 H CH _x
5 H. CH-,
5 H CH ₃ H CH ₃ H CH _x
5 H CH ₃ H CH _x
3 H CH _x
3 H CH _x
5 H CH ₃ H

Sum formula

C ₁₄ H ₁₅ N ₅ O

^C 15 ^H 15 ^N 5

^C 12 ^H 12 ^N 6

C ₁₀ H ₁₅ N ₅

C _n H ₁₇ N ₅ O

C ₉ H ₁₃ N ₅ O

C ₉ H ₁₃ N ₅

223203 _N 8

Ber.

27.7

28.8

55.1

26.0

29.5

36.6

34.1

Found

27.7

52.7

25.7

28.9

55.0 54.4 54.1 55.9 29.7 29.8 55.9 55.4 55.8 55.5 52.1 52.0 40.8 40.0

309882/1355

56.1

33.8

- 10

X y Z N
^ C ₅ H ₇ CH _x
3 H ^ CHg-CHg-OH ^H 3 II / CH ₅ CH _x
. 3 H / CH ₀ ^ CH ₀ -OH
• Ν ^dd
^ CHg-CHg-OH CH ₅ H CH _x
3 H • ⁿ S> ■■■ CH ₅ H • N HN -CH ₅ ': - . 3 H * ϊ / H CH _x
3 H ^ C, H (n)
^ -CHg-CHg-OH CH _x
3 H Γη)
-N «
^ CHg-CHg-OH CH ₅ H -NH- (CHp) ₅ -NII b CH,
3 H CH ₇
ι 3
-N - NHg CH ₅ H

2232038 "Found - Suirmienf orrael ^N Ber, 28.3 O ₁₅ H ₂₁ N ₅ 28.3 .31.0 O ₁₀ H ₁₅ N ₅ O 31.6 27.5 O _M H ₁₅ N ₅ ■ ^ 27.7 "27.4 27.9 29.9 O ₁₁ H ₁₅ N ₅ O 30.0 30.0 30.3 33.9 C ₁₂ H ₁₈ Ng 31.7 ^C 11 ^H I ₅ V 32.2 26.5 O ₁₃ H ₂₁ N ₅ O 26.6 24.0 C * TT ΪΓ C \ 24- ■ 2 28.8 C ₁₄ H ₂₂ N ₆ O 29.0 42.9 C ₈ H ₁₂ N ₆ 43.8.

3098 82 / 135B

- 11

X Y .Z η
Snnrnenf or me 1 2232C
^N Ber. 138 / CH _x
KH-N ^
3 CH _x
3 H We '40.8 40.1 NH-N "^ ^{2 5} CH _x
3 H ° 11 ^H 18 ^K 6 35.9 . 35.7 ΝΗ-ΝΗ- / ~ Λ 3 H <33.1 33.0 NH-N h \ CH _x
3 H ° 12 »18% 34.1 33.9 NH-N IO CH _x
3 H We » 33.9 33.3 HH-N H
\ CH _x H ^C 11 ^H 16 ^N 6 36.2 35.7 CH, H ^C 10 ^H 16 ^N 6. 38.2 37.6 f ^H 3 / CH _x
NN ^? CH _x H 39.1 39.0 NH - OH _:. CH _x
3 H C ₉ H ₁₃ N ₅ O 33.8 33.2 ^ CH ₇
N ->
3 CH _x
3 II 29.5 29.5 / CH ₀ -CH ₀ -OH
N ^ ^
"^ 0CH _x
3 CH _x
3 H 29.8 29.4 N ^ ² " ³ CH _x
3 H "32.0 31.6 CH ₀ - CH ₀
I ² I ²
N CH ₂ CH _x
3 H 30.0 29.5 <s> ■

309882 / 13SS

- 12 -

Z Sum formula ^N Calc. ^N Gef.

- OCH ₂ -CH ₂ -OCH

-O-CH

• ". 'Θ

ΌΗ,

CII-

CH,

CH

-α / Λ

- O-CH ₀ -CH ₀ -OH

₂ -CH ₂

- NS,

CH,

CH,

CH,

• CH,

CH,

-OH,

CH,

-NHCH,

(DD

C ₉ H ₁₂ N ₄ O

^C 10 ^H lA ° 2

^C 10 ^H lA °

C ₁₃ H ₁₇ N ₄ O

C ₉ H ₁₂ N ₄ O ₂

C ₈ H ₁₀ N ₄ S

C ₁₃ H ₁₂ N ₄ S

C ₁₁ H ₁₇ N ₅ O

C ₁₀ H ₁₄ N ₄ O ₂

C ₁₅ H ₂₂ N ₄ O

C ₁₄ H ₁₅ N ₅

29.2

25.2

27.2

29.8 25.2

19.3 27.7

28.9

24.8

27, o

22.9 22.8 22.0 22.1 23.3 23.0 26.9 26.7 28.9 28.6 26.9 27.0 21.9 21.6 28.3 28.1

29.3

25.1

19.0 27.5

- 13 -

309882/1355

_N H ₂ . -O- Z Suimnenform 2232038 30.5 ΝΗ- / Λ Q-ci ■ H O ₁₂ H ₁₁ H ₅ ^W Ber. 20.7 X Y N (CH ₅ ) ₂ H 31.1 28.7 NS-,
3 OH ₂ ^ H C ₁₂ H ₁₃ N ₅ O 20.9 25.5
t <c ° i ₅ ⁵ CH,
3 H C ₁₃ H ₁₃ N ₅ S 28.8 30.2 NH-CH ₂ -CH ₂ -OH ⁰ V. CH,
3 ^c i2 ^H i9 ^N 5 25.9. 29.4 / CH,
N °
^ CH ₂ -CH ₂ -OH CH ₃ O ₂ H ₅ C _n H ₁₇ N ₅ O ' 30.0 26.5 C ₃ H ₇ C ₁₃ H ₂₁ N ₅ O 29.8 26.6

309882/1355

Claims (3)

Claims:> 1. 3-Amino-1H-pyrazoloC3,4-b] pyridines of the formula wherein X is a primary, secondary or tertiary amino group, a Hydrazino, a hydroxylamino, an ether or thio ether group, Y is hydrogen, an optionally substituted alkyl, Cycloalkyl, aryl or heterocyclic radical and Z is hydrogen or an alkyl radical. 2. Process for the preparation of 3 ~ amino-1H-pyrazolo [3,4 ~ bJpyx * idynes the formula wherein X is a primary, secondary or tertiary amino group, a hydrasino, a hydroxylamino, an ether or thioether group, Y is hydrogen, an optionally substituted alkyl, Cycloalkyl, aryl or heterocyclic radical and Z is hydrogen or an alkyl radical, characterized in that one a 2,6-dihalo-5-cyanopyridine of the formula Hal ^ "N '" ^Hal wherein Y has the meaning given above and Hai'ein chlorine or Bromine atom means with ammonia, a primary or secondary amine, a hydrazine, a hydroxylamine, a hydroxy ~ or Mercapto compound converts and the compound thus obtained of the formula 3 09882/1355 - 15 - CN Hal wherein X, Y and Hal have the meaning given above, rait a hydrazine of the formula condensed. ·. ' 3. The use of the compounds geraäss claim 1 for Manufacture of dyes, pesticides . ..or pharmaceuticals. 309882/1