7-Amino-5-Halopyrazolopyrimidines with a Fungicidal Action

Abstract

Novel pyrazolopyrimidines of the formula

Description

PREPARATION EXAMPLES

Example 1

Process (a):

At 0° C., 1.0 g (0.004 mol) of 3-cyano-5,7-dichloro-6-(sec-butyl)pyrazolo[1,5-a]pyrimidine is added with stirring to a solution of 0.389 g (0.004 mol) of (S+)-3-methyl-2-butylamine in 0.451 g (0.004 mol) of triethylamine and 20 ml of dichlorethane. The reaction mixture is stirred at room temperature for 16 hours and then, with stirring, poured into water. The resulting mixture is acidified by addition of hydrochloric acid and extracted with dichlormethane. The combined organic phases are dried over sodium sulfate and then concentrated under reduced pressure. The residue that remains is chromatographed on silica gel using cyclohexane:ethyl acetate =8:2. This gives 0.8 g (64.3% of theory) of 3-cyano-5-chloro-6-(sec-butyl)-7-[(S+)-3-methyl-2-butylamino]pyrazolo[1,5-a]pyrimidine.

HPLC: logP=4.59

Example 2

Process (a):

At room temperature, 0.51 g of potassium carbonate and 0.32 g of 3-methyl-2-butylamine are added successively with stirring to a mixture of 1 g of 3-formyl-5,7-dichloro-6-(sec-butyl)-pyrazolo[1,5-a]pyrimidine and 30 ml of acetonitrile. The reaction mixture is stirred at room temperature for 12 hours and then, with stirring, poured into water. The resulting mixture is extracted three times with ethyl acetate. The combined organic phases are dried over sodium sulfate and then concentrated under reduced pressure. The residue that remains is chromatographed on silica gel using cyclohexane:ethyl acetate=4.1. This gives 0.14 g (9.2% of theory) of 3-formyl-5-chloro-6-(sec-butyl)-7-(3-methyl-2-butylamino)pyrazolo[1,5-a]pyrimidine.

HPLC: logP=4.17

The pyrazolopyrimidines of the formula

listed in table 1 below are/were also obtained by the methods described above.

TABLE 1
Ex.No.		R3	R4	Hal	R5	logP *)
3		H	—CN	Cl		3.90
4		H	—CN	Cl		4.62
5		H	—COOCH3	Cl		3.76
6		H	—COOCH3	Cl		4.49
7		H	—COOCH3	Cl		4.49
8		H		Cl
9		H		Cl
10		H		Cl
11		H		Cl
12		H		Cl
13		H		Cl
14		H		Cl
15		H		Cl
16		H	—CN	Cl
17		H	—CN	Cl
18		H		Cl
19		H		Cl
20		H		Cl
21		H		Cl
22		H		Cl
23		H		Cl
24		H		Cl
25		H		Cl
26		H		Cl
27		H		Cl
28		H		Cl
29		H		Cl
34		H	—CN	Cl
35		H	—CN	Cl
36		H	—CN	Cl
37		H	—COOCH3	Cl
38		H	—COOCH3	Cl
39		H		Cl
40		H		Cl
41		H		Cl
42		H		Cl
43		H		Cl
44		H		Cl
45		H		Cl
46		H		Cl
47		H		Cl
48		H		Cl
49		H	—CN	Cl
50		H	—CN	Cl
51		H	—CN	Cl
52		H	—COOCH3	Cl
53		H	—COOCH3	Cl
54		H	—COOCH3	Cl
55		H	—COOCH3	Cl
56		H	—COOCH3	Cl
57		H		Cl
58		H		Cl
59		H		Cl
60		H		Cl
61		H		Cl
62		H		Cl
63		H		Cl
64		H		Cl
65		H		Cl
66		H		Cl
67		H	—CN	Cl
68		H	—CN	Cl
69		H	—CN	Cl
70		H	—CN	Cl
71		H	—CN	Cl
72		H	—COOCH3	Cl
73		H	—COOCH3	Cl
74		H	—COOCH3	Cl
75		H	—COOCH3	Cl
76		H	—COOCH3	Cl
77		H		Cl
78		H		Cl
79		H		Cl
80		H		Cl
81		H		Cl
82		H		Cl
83		H		Cl
84		H		Cl
85		H		Cl
86		H		Cl
87		H		Cl
88		H		Cl
89		H		Cl
90		H		Cl
91		H		Cl
92		H		Cl
93		H		Cl
94		H		Cl
95		H		Cl
96		H		Cl
97		H	—CN	Cl
98		H	—CN	Cl
99		H	—CN	Cl
100		H	—CN	Cl
101		H	—CN	Cl
102		H	—COOCH3	Cl
103		H	—COOCH3	Cl
104		H	—COOCH3	Cl
105		H	—COOCH3	Cl
106		H	—COOCH3	Cl
107		H		Cl
108		H		Cl
109		H		Cl
110		H		Cl
111		H		Cl
112		H		Cl
113		H		Cl
114		H		Cl
115		H		Cl
116		H		Cl
117		H		Cl
118		H		Cl
119		H		Cl
120		H		Cl
121		H		Cl
122		H		Cl
123		H		Cl
124		H		Cl
125		H		Cl
126		H		Cl
127		H	—CN	Cl
128		H	—CN	Cl
129		H	—CN	Cl
130		H	—CN	Cl
131		H	—CN	Cl
132		H	—COOCH3	Cl
133		H	—COOCH3	Cl
134		H	—COOCH3	Cl
135		H	—COOCH3	Cl
136		H	—COOCH3	Cl
137		H		Cl
138		H		Cl
139		H		Cl
140		H		Cl
141		H		Cl
142		H		Cl
143		H		Cl
144		H		Cl
145		H		Cl
146		H		Cl
147		H		Cl
148		H		Cl
149		H		Cl
150		H		Cl
151		H		Cl
152		H		Cl
153		H		Cl
154		H		Cl
155		H		Cl
156		H		Cl
157		H	—CN	Cl
158		H	—CN	Cl
159		H	—CN	Cl
160		H	—CN	Cl
161		H	—CN	Cl
162		H	—COOCH3	Cl
163		H	—COOCH3	Cl
164		H	—COOCH3	Cl
165		H	—COOCH3	Cl
166		H	—COOCH3	Cl
167		H		Cl
168		H		Cl
169		H		Cl
170		H		Cl
171		H		Cl
172		H		Cl
173		H		Cl
174		H		Cl
175		H		Cl
176		H		Cl
177		H		Cl
178		H		Cl
179		H		Cl
180		H		Cl
181		H		Cl
182		H		Cl
183		H		Cl
184		H		Cl
185		H		Cl
186		H		Cl
*) logP values were determined in accordance with EEC Directive 79/831 Annex V. A8 by HPLC (gradient method, acetonitrile/0.1% aqueous phosphoric acid)

Preparation of Starting Materials

Example 30

Process (e):

At room temperature, 10.976 g of phosphorus pentachloride are added with stirring to a mixture of 21.477 g (0.092 mol) of 3-cyano-5,7-dihydroxy-6-(sec-butyl)pyrazolo[1,5-a]pyrimidine and 126. 196 g (0.823 mol) of phosphorus oxychloride. The reaction mixture is heated at 110° C. for 3 hours and then concentrated under reduced pressure. The residue that remains is dissolved in dichloromethane. The resulting solution is initially washed with ice-water and then dried over sodium sulfate and concentrated under reduced pressure. The residue that remains is chromatographed on silica gel using petroleum ether:tert-butyl methyl ether=2:1. This gives 9.4 g (33%) of theory) of 3-cyano-5,7-dichloro-6-(sec-butyl)pyrazolo[1,5-a]pyrimidine.

HPLC: logP=3.27

Example 31

Process (f):

A mixture of 15 g of 5,7-dihydroxy-6-(sec-butyl)pyrazolo[1,5-a]pyrimidine and 35 ml of phosphorus oxychloride is heated under reflux for 1 hour and then cooled to 0° C. 10.6 g of dimethylformamide are then added dropwise with stirring to the reaction mixture such that the temperature of the mixture does not exceed 20° C. After the addition has ended, the mixture is initially stirred at room temperature for 1 hour and then heated under reflux for 2 hours. The mixture is then concentrated under reduced pressure. The residue that remains is stirred with ice-water and the resulting mixture is extracted with ethyl acetate. The combined organic phases are dried over sodium sulfate and then concentrated under reduced pressure. The residue that remains is dissolved in ethyl acetate and filtered through silica gel. This gives 7 g of 3-formyl-5,7-dichloro-6-(sec-butyl)pyrazolo[1,5-a]pyrimidine. The product is used without additional purification for further synthesis.

Example 32

Process (g):

A mixture of 20.0 g (0.092 mol) of diethyl sec-butylmalonate, 9.997 g (0.092 mol) of 4-cyano-5-amino-1H-pyrazole and 18.854 g (0.102 mol) of tri-n-butylamine is heated under reflux at 180° C. for 6 hours. Ethanol liberated during the reaction is continuously distilled off. The reaction mixture is then concentrated under reduced pressure. This gives 21.5 g (100% of theory) of 3-cyano-5,7-dihydroxy-6-(sec-butyl)pyrazolo[1,5-a]pyrimidine. The product is used without additional purification for further syntheses.

The pyrazolopyrimidines of the formula (II) listed in table 2 below are also obtained by the methods described above:

Ex.
No.	Y1	R3	R6	Hal	R5	logP*)
33	Cl	H	—COOCH3	Cl		3.13

Use Examples

Example A

Venturia—Test (Apple)/Protective

Solvents:	24.5	parts by weight of acetone
	24.5	parts by weight of dimethylacetamide
Emulsifier:	1.0	part by weight of alkylaryl polyglycol ether

To produce a suitable preparation of active compound, one part weight of active compound is mixed with the stated amounts of solvents and emulsifier, and the concentrate is diluted with water to the desired concentration.

To test for protective activity, young plants are sprayed with the preparation of active compound at the stated application rate. After the spray coating has dried on, the plants are inoculated with an aqueous conidia suspension of the apple pathin Venturia inaequalis and then remain in an incubation cabinet at about 20° C. and 100% relative atmospheric humidity for one day.

The plants are then placed in a greenhouse at about 21° C. and a relative atmospheric humidity of about 90%.

Evaluation is carried out 10 days after the inoculation. 0% means an efficacy which corresponds to that of the control, whereas an efficacy of 100% means that no infection is observed.

In this test, the compounds according to the invention listed in examples 1, 3 and 4 showed, at an application rate of 100 g/ha, an efficacy of more than 80%.

Example B

Botrytis—Test (Bean)/Protective

Solvents:	24.5	parts by weight of acetone
	24.5	parts by weight of dimethylacetamide
Emulsifier:	1.0	part by weight of alkylaryl polyglycol ether

To produce a suitable preparation of active compound, one part by weight of active compound is mixed with the stated amounts of solvents and emulsifier, and the concentrate is diluted with water to the desired concentration.

To test for protective activity, young plants are sprayed with the preparation of active compound at the stated application rate. After the spray coating has dried on, two small pieces of agar colonized by Botrytis cinerea are placed onto each leaf. The inoculated plants are placed in a dark chamber at about 20° C. and 100% relative atmospheric humidity.

The size of the infected areas on the leaves is evaluated 2 days after the inoculation. 0% means an efficacy which corresponds to that of the control, whereas an efficacy of 100% means that no infection is observed.

In this test, the compounds according to the invention listed in examples 1 and 4 showed, at an application rate of 500 g/ha, an efficacy of more than 80%.

Example C

Erysiphe Test (Barley)/Protective

Solvent:	49	parts by weight of N,N-dimethylacetamide
Emulsifier:	1.0	part by weight of alkylaryl polyglycol ether

To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.

To test for protective activity, young plants are sprayed with the preparation of active compound at the stated application rate. 1 day after the treatment, the plants are inoculated with spores of Erysiphe graminis f. sp. hordei. The plants are then placed in a greenhouse at 70% relative atmospheric humidity and a temperature of 18° C.

Evaluation is carried out 7 days after the inoculation. 0% means an efficacy which corresponds to that of the control, whereas an efficacy of 100% means that no infection is observed.

In this test, the compound according to the invention listed in example 3 showed, at an application rate of 750 g/ha, an efficacy of more than 80%.

Claims

1. A pyrazolopyrimidine of the formula

2. The pyrazolopyrimidine of the formula (I) as claimed in claim 1 in which R1 represents alkyl having 1 to 6 carbon atoms which may be mono- to pentasubstituted by identical or different substituents selected from the group consisting of halogen, cyano, hydroxy, alkoxy having 1 to 4 carbon atoms and cycloalkyl having 3 to 6 carbon atoms, orR1 represents alkenyl having 2 to 6 carbon atoms which may be mono- to trisubstituted by identical or different substituents selected from the group consisting of halogen, cyano, hydroxy, alkoxy having 1 to 4 carbon atoms and cycloalkyl having 3 to 6 carbon atoms, orR1 represents alkinyl having 3 to 6 carbon atoms which may be mono- to trisubstituted by identical or different substituents selected from the group consisting of halogen, cyano, alkoxy having 1 to 4 carbon atoms and cycloalkyl having 3 to 6 carbon atoms, orR1 represents cycloalkyl having 3 to 6 carbon atoms which may be mono- to trisubstituted by identical or different substituents selected from the group consisting of halogen and/or alkyl having 1 to 4 carbon atoms, orR1 represents saturated or unsaturated heterocyclyl having 5 or 6 ring members and 1 to 3 heteroatoms, where the heterocyclyl may be mono- or disubstituted by halogen, alkyl having 1 to 4 carbon atoms, cyano, nitro or cycloalkyl having 3 to 6 carbon atoms,R2 represents hydrogen or alkyl having 1 to 4 carbon atoms, orR1 and R2 together with the nitrogen atom to which they are attached represent a saturated or unsaturated heterocyclic ring having 3 to 6 ring members, where the heterocycle may contain a further nitrogen, oxygen or sulfur atom as a ring member and where the heterocycle may be substituted up to 3 times by fluorine, chlorine, bromine, alkyl having 1 to 4 carbon atoms or haloalkyl having 1 to 4 carbon atoms and 1 to 9 fluorine and/or chlorine atoms,R3 represents hydrogen, fluorine, chlorine, bromine, iodine, alkyl having 1 to 4 carbon atoms, haloalkyl having 1 to 4 carbon atoms and 1 to 4 halogen atoms or cycloalkyl having 3 to 6 carbon atoms,R4 represents cyano, fluorine, chlorine, bromine, iodine, nitro, formyl, haloalkyl having 1 to 4 carbon atoms and 1 to 9 fluorine, chlorine or bromine atoms, alkyl having 1 to 4 carbon atoms, hydroxyalkyl having 1 to 4 carbon atoms, alkoxyalkyl having 1 to 4 carbon atoms in the alkoxy moiety and 1 to 4 carbon atoms in the alkyl moiety, cycloalkyl having 3 to 6 carbon atoms, thiocarbomoyl, alkoxycarbonyl having 1 to 4 carbon atoms in the alkoxy moiety, alkylcarbonyl having 1 to 4 carbon atoms in the alkyl moiety, benzylcarbonyl, cycloalkylcarbonyl having 3 to 6 carbon atoms in the cycloalkyl moiety, hydroximinoalkyl having 1 to 4 carbon atoms in the alkyl moiety, alkoximinoalkyl having 1 to 4 carbon atoms in the alkoxy moiety and 1 to 4 carbon atoms in the alkyl moiety, alkylthio having 1 to 4 carbon atoms, alkylsulfinyl having 1 to 4 carbon atoms, alkylsulfonyl having 1 to 4 carbon atoms or alkylaminocarbonyl having 1 to 4 carbon atoms in the alkyl moiety, Hal represents fluorine, chlorine or bromine andR5 represents alkyl having 1 to 6 carbon atoms, alkenyl having 2 to 6 carbon atoms, cycloalkyl having 3 to 8 carbon atoms, cycloalkenyl having 3 to 8 carbon atoms, haloalkyl having 1 to 6 carbon atoms and 1 to 5 fluorine, chlorine or bromine atoms, haloalkenyl having 2 to 6 carbon atoms and 1 to 5 fluorine, chlorine or bromine atoms, cycloalkyl which has 3 to 8 carbon atoms and is substituted by 1 to 3 fluorine, chlorine or bromine atoms or cycloalkenyl which has 3 to 8 carbon atoms and is substituted by 1 to 3 fluorine, chlorine or bromine atoms.

3. The pyrazolopyrimidine of the formula (I) as claimed in claim 1 in which R1 represents a radical of the formula

4. The pyrazolopyrimidine of the formula (I) as claimed in claim 1, in which R3 represents hydrogen, fluorine, chlorine, bromine, methyl, ethyl, propyl, isopropyl, trifluoromethyl or cyclopropyl andR5 represents methyl, ethyl, propyl, isopropyl, n-butyl, i-butyl, sec-butyl, tert-butyl, allyl, but-2-en-1-yl, cyclopropyl, cyclopentyl, cyclohexyl, cyclopentenyl, cyclohexenyl, chloromethyl, trifluoromethyl, trifluoroisopropyl, trichloroallyl, 2,2-dichlorocyclopropyl or dichloro-cyclohexenyl.

5. A process for preparing pyrazolopyrimidines of the formula (I) as claimed in claim 1, comprising characteried in that (a) reacting halopyrazolopyrimidines of the formula

6. A composition for controlling unwanted microorganisms, comprising at least one pyrazolopyrimidine of the formula (I) according to claim 1, and extenders or surfactants.

7. The composition as claimed in claim 6, comprising at least one further fungicidally or insecticidally active compound.

8. (canceled)

9. A method for controlling unwanted microorganisms, comprising contacting unwanted microorganisms or their habitat with pyrazolopyrimidines of the formula (I) as claimed in claim 1.

10. A process for preparing compositions for controlling unwanted microorganisms, comprising mixing a pyrazolopyrimidine of the formula (I) as claimed in claim 1 with extenders or surfactants.