The way to obtain 2-substituted 4,6-dialkoxybenzene,2-n - butylamino-4,6-dimethoxypyrimidine and method for producing halogenated derivatives of pyrimidine

 

(57) Abstract:

Use as intermediates for obtaining herbicides. Method for obtaining 2-substituted 4,6-dialkoxybenzene formula I, where R1and R2- same or different (C1-C4)-alkyl, R3-R4-O-, R4-S - or R4R5N-, where R4- (C1-C4)-alkyl, R5is hydrogen, (C1-C4)-alkyl or phenyl, by cyclization of cyanamide formula II with halogenation with the formation of halogen derivatives of pyrimidine of the formula III, which by reacting with the compound of the formula IV M-R3where R3= R4-O - or R4-S-, M - atom, alkali metal, or alkylamino formula , transferred to the target compound of formula I. the Described 2-N-butylamino-4,6-dimethoxypyrimidine.

< / BR>
< / BR>
< / BR>
3 S. and 7 C. p. F.-ly, 1 table.

The invention relates to a new method of obtaining 2-substituted 4,6-dialkoxybenzene General formula I

< / BR>
in which

R1and R2may be the same or different and mean (C1-C4)-alkyl, and R3means R4-O-, R4-S - or R4R5N-, where R4equal to C1-C4-alkyl, R5osnia halogen-substituted pyrimidine.

These 2-substituted 2,6-dialkoxybenzene, in particular 4,6-dimethoxy-2-(methylthio)pyrimidine, are important intermediates for obtaining herbicides (European patent A 249 708).

A method of obtaining halogen derivatives of pyrimidine, in particular 2-chloro-4,6-dialkoxybenzene by diazotization of 2-amino-4,6-dialkoxybenzene of sodium nitrite, followed by hydrolysis of the resulting compound with concentrated hydrochloric acid (J. A. Bee and F. L. Rose, J. Chem. Soc., C, 1966, S. 2031).

A big disadvantage of this method is the very low yield of the desired 2-chloro-4,6-dimethoxypyrimidine.

Also known is a method of obtaining 4,6-dialkoxy-2-alkyldiphenylamine using as starting compound 4,6-dioxopyrimidine and organic sulfonic acids as described in Japanese patent A-01040470.

This method allows to obtain 4,6-dialkoxy-2-alkylthiophenes with very low output.

It is also known that 4,6-dimethoxy-2-(methylthio)pyrimidine can be obtained by substitution of 4,6-dichloro-2-methylthiopyrimidine of chlorine atoms with an alkali metal methylate. According to this method, first get the original connection of 4,6-dichloro-2-methylthiopyrimidin chlororespiration ways, with the help of an alkali metal methylate, transferred to 4,6-dimethoxy-2-(methylthio)pyrimidine.

This method has the disadvantage that when implementing it as a waste produces large quantities of phosphate, which must be disposed of.

The invention aims to remedy these disadvantages by creating a simple and environmentally friendly method of producing 2-substituted 4,6-dialkoxybenzene with high outputs.

Thus, the invention relates to a new method of obtaining 2-substituted 4,6-dialkoxybenzene General formula I

< / BR>
in which

R1and R2may be the same or different and mean (C1-C4)-alkyl, and R3means R4-O-, R4-S - or R4R5N-, where R4means (C1-C4)-alkyl, and R5means a hydrogen atom or a (C1-C4)-alkyl or phenyl. The method consists in the fact that in the first stage of the process is carried out cyclization of cyanamide General formula II

< / BR>
in which

R1and R2have the specified values, with halogenation with the formation of the halogen derivatives of pyrimidine of the General formula III

< / BR>
in which

R< the interaction with the compound of General formula IV

M - R3< / BR>
in which

R3means videopreteen group R4-O or R4-S-, and M means an alkali metal atom, or alkylamino General formula V

< / BR>
in which

R4and R5have the above meanings, is transferred to the target compound of formula I.

Mainly as cyanimide using 3-amino-3-methoxy-N-cyano-2-propenamide formula II, where R1and R2means methyl.

As halogenated it is desirable to use hydrogen chloride.

Usually the reaction in the first stage is carried out at (-30) - (30)oC.

As compounds of General formula IV in the second stage uses tiolet or methanolate alkali metal.

In the second stage of the method, it is desirable to use alkylamine General formula V in which R4means butyl, and R5- the hydrogen atom.

Typically, the reaction in the second stage of the method is carried out at -10 - 100oC.

Usually the reaction is performed without allocating a halogen derivative of a pyrimidine of formula III from the reaction mixture.

When carrying out the first stage it is advisable to use as source material imidate total HUF is as imidate formula II is 3-amino-3-methoxy-N-cyano-2-propenamide, in which R1and R2means methyl.

The specified 3-amino-3-methoxy-N-cyano-2-propenamide may be, for example, is easily obtained by the method in accordance with the European patent 024200.

As galgenwaard in the first stage, you can use hydrogen chloride, hydrogen bromide or modesty hydrogen. Preferred is the use of hydrogen chloride.

Galgenwaard when interacting with cyanamide formula II can be taken in amounts of 2 to 4 mol per mol of the latter. Preferably gaseous halogenated passed through the reaction mixture until saturation.

The reaction in the first stage it is advisable conducts at a temperature of -30 and 30oC, preferably -20 and 10oC.

As solvent in the first stage it is possible to use organic solvents, such as, for example, tetrahydrofuran, toluene, acetonitrile, methylene chloride or low-boiling alcohols. The preferred solvent is toluene.

After the reaction within, typically, 1-5 h obtained halogenated derivatives of pyrimidine of formula III can be processed by conventional means or directly without isolation of the Hai, it is advisable to use as a starting compound of General formula IV

M - R3< / BR>
have

R3means methoxy or ethoxypropan (preferably methoxy) or methyl - or ethylthiourea, and M is an alkali metal atom.

The preferred compound of formula IV is methanolate sodium and potassium and tiolet sodium and potassium.

When conducting the reaction in the second stage it is advisable to use as an alkylamine of the General formula V

< / BR>
compounds in which R4means C1-C4-alkyl, and R5- C1-C4-alkyl or a hydrogen atom. Preferably as alkylamine to use butylamine (in this case, R4means butyl, and R5- the hydrogen atom).

Compounds of General formula IV or V can be used in the amount of 1-3, preferably 1 to 2 mol per mol of halogen derivatives of pyrimidine of formula III.

The reaction in the second stage is useful to -10 - 100oC, preferably 40 to 80oC.

The solvent in the second stage you can use the same solvents as on the first.

After the reaction for typically 1-50 h produced the desired product of formula I may be subjected to further processing in the usual ways.mules III.

Another object of the invention is 2-N-alkylamino-4,6-dialkoxybenzene General formula I, particularly preferred 2-N-butylamino-4,6-dimethoxypyrimidine.

The object of the invention is also a method of obtaining halogen derivatives of pyrimidine of the General formula III

< / BR>
in which

R1and R2may be the same or different and mean (C1-C4)-alkyl, X is halogen atom, namely, that cyanimide General formula II

< / BR>
in which

R1and R2have the above meanings, is subjected to interaction with halogenation.

Example 1. Getting 2-chloro-4,6-dimethoxypyrimidine

a) Using the solvent of tetrahydrofuran.

4.7 g of 3-amino-3-methoxy-N-cyano-2-propenamide suspended in 60 ml of tetrahydrofuran and cooled the resulting suspension to -20oC. thereafter through it missed gaseous hydrogen chloride until saturation, while maintaining the temperature within the (-10) to (20)oC. for 3 h every 30 min through a solution of missed this amount of gaseous hydrogen chloride, so that he was again saturated. Then the tetrahydrofuran was fully off, the residue after addition of sodium was evaporated to dryness. The result has been 4,0 white crystalline product with a yield of 71.1% in the calculation of the original propenamide. The melting point of 99 - 100oC. the Content of the target compounds in the resulting product 94% (for a given gas chromatography).

The resulting product can be recrystallized as follows.

Obtained as described above crude pyrimidine were heated in 25 ml isopropanol to 70oC. After adding to the obtained solution of water prior to the dimness it was cooled to 10oC and drop precipitate was filtered. After drying was obtained 3.5 g of pure product, which was 66.2% in the calculation of the original propenamide. Melting point 102oC. the Content of the target compounds in the product 99% (according to gas chromatography).

The results of elemental analysis calculated for the formula C6H7ClN2O2< / BR>
Found.% C 40,8; H 4,0; N 16,0

Calculated,% 41,3 C; H 4,0; N 16,1

1H-NMR (CDCl3, 300 MHz memorial plaques: 5,97 (s, 1H), 3,95 (s, 6H).

b) Using as solvent toluene.

A suspension of 2.4 g of 3-amino-3-methoxy-N-cyano-2-propenamide in 20 ml of toluene was saturated at 0oC gaseous hydrogen chloride. Suspension Perama remained intense. Then to the reaction mixture were added 20 ml of water, the phases were separated and the aqueous phase twice more was subjected to extraction with toluene, in portions of 10 ml the combined organic phases were evaporated to dryness and the residue was dried in high vacuum. The result was obtained 2.1 g of white crystalline product with a content of the target compounds (according to gas chromatography) 95%, which corresponded to the output 73,9 in the calculation of the original propenamide. Melting point 100oC.

Example 2. Getting 4,6-dimethoxy-2-methylthiopyrimidine

2-Chloro-4,6-dimethoxypyrimidine was obtained as described in example 1. Obtained after extraction the organic phase was added at room temperature dropwise to a solution of 1.5 mol equivalent of thiolate of sodium in 5 ml of methanol. To complete the reaction, the reaction mixture was heated for 2 h to 50oC and kept for two hours at this temperature.

After extraction with 20 ml of water, evaporation and drying of the residue in high vacuum was obtained 1.8 g of white crystalline product, which corresponded to a yield of 60% (based on the original propenamide. The melting point of 49 - 50oC. By recrystallization from a mixture of isopropanol and water received PR is,55 (C, 3H).

Example 3. Getting 2-N-butylamino-4,6-dimethoxypyrimidine

A solution of 1.9 g of 2-chloro-4,6-dimethoxypyrimidine in 30 ml of toluene according to example 1B was mixed with 2.7 g of butylamine and 3.3 g of triethylamine and the mixture was heated for 50 hours at 80oC. After cooling, it was twice subjected to extraction with water, 30 ml, and the organic phase was evaporated to dryness. The remainder in the form of a yellowish oily liquid was distilled at 140oC and pressure in mbar. The result was obtained 2.1 g of colorless oily liquid, which corresponded to a yield of 66% in the calculation of the original preranked. The content of the target compounds in the resulting product 98% (according to gas chromatography).

1H-NMR (CDCl3, 300 MHz) in M. D.: 5,4 (C. 1H), 4.95 points (b, 1H), 3,85 (s, 6H), 3,4 (square, 2H), 1,4 (m, 2H), of 0.95 (t, 3H).

The results of elemental analysis calculated for the formula C10H17N3O2< / BR>
Found,% C 56,9; H 8,5; N 19,6

Calculated% C 56,9; H 8,1; N 19,9

Example 4. Getting 2,4,6-trimethoxyaniline

1.3 g of 2-Chloro-4,6-dimethoxypyrimidine obtained in example 1a (content 94%) was dissolved in 9 ml of methanol. After adding 2.5 g of a 30% methanolic solution of methanolate sodium and the mixture was stirred for 2 h at 55oC the Institute in an ice bath was the crystallization of the product as fine white needles, which was filtered and dried under vacuum at room temperature. The result has been 1,02 g of pure product, which corresponded to a yield of 86%. Melting point 55oC.

1H-NMR (CDCl3, 300 MHz) in M. D.: 5,7 (s, 1H), 4.0 (with C. 3 H), 3,95 (C. 6H).

Analogously to example 1 by reaction of 2-chloro-4,6-diethoxybenzene obtained in example 3, with the corresponding aminoguanidinium were obtained products are shown in the table.

1. Way to obtain-2-substituted 4,6-dialkoxybenzene General formula I

< / BR>
in which R1and R2may be the same or different and mean C1- C4-alkyl, and R3means R4-O, R4-S - or R4R5N-, where R4means C1- C4-alkyl, and R5means a hydrogen atom, a C1- C4-alkyl or phenyl group,

characterized in that the first stage of the process is carried out cyclization of cyanamide General formula II

< / BR>
in which R1and R2have the specified values,

with halogenation with the formation of the halogen derivatives of pyrimidine of the General formula III

< / BR>
in which R1and R2have the above meanings, and X is the halogen atom is in which R3means videopreteen group R4-O - or R4-S-, and M means an alkali metal atom,

or alkylamino General formula

< / BR>
in which R4and R5have the specified values,

transferred to the target compound of formula I.

2. The method according to p. 1, characterized in that the first stage of the method as cyanimide using 3-amino-3-methoxy-N-cyano-2-propenamide formula II, where R1and R2means methyl.

3. The method according to p. 1 or 2, characterized in that the first stage of the method as halogenated use of hydrogen chloride.

4. The method according to one of paragraphs.1 to 3, characterized in that the reaction in the first stage is carried out at (-30) - (30)oC.

5. The method according to p. 1, characterized in that in the second stage of the way as the compounds of General formula IV use tiolet or methanolate alkali metal.

6. The method according to p. 1, characterized in that in the second stage of the method used alkylamine General formula V, in which R4means butyl, and R5- the hydrogen atom.

7. The method according to PP.1 - 6, characterized in that the reaction in the second stage of the method is carried out at (-10) - (100)oC.

8. The method according to one of paragraphs.1 to 4, different the LASS="ptx2">

9. 2-N-butylamino-4,6-dimethoxypyrimidine.

10. The method of obtaining halogen derivatives of pyrimidine of the General formula II

< / BR>
in which R1and R2may be the same or different and mean C1- C4-alkyl, and X denotes a halogen atom,

characterized in that cyanimide General formula II

< / BR>
in which R1and R2have the above meanings, is subjected to interaction with halogenation.

 

Same patents:

The invention relates to organic chemistry, specifically to new chemical compound 5-hydroxy-3,6-dimethyluracil formula

< / BR>
showing membrane and antiradical activity

The invention relates to a method for producing 5-[3(4)-R-1-substituted]pyrimidines of General formula:

< / BR>
where R1, R2= H, lower alkyl, phenyl, substituted SN3, CF3, Cl-group; R3, R4, R5= N, hydroxyalkyl - or amino-group;

which can find wide application in the synthesis of biological active substances in medicine

The invention relates to new derivatives of pyrimidine or triazine and their salts, in particular derivatives of pyrimidine or triazine represented by the General formula I, and also relates to a herbicide composition containing these derivatives, pyrimidine or triazine or their salts as active substances, which can be used on rysownika, soils upland conditions or space not occupied for agricultural crops

The invention relates to the field of organic chemistry, specifically to new chemical compound 5-hydroxy-3,6-dimethyluracil formula

showing immunotropic activity

Ammonium salts // 2106346

The invention relates to an improved process for the preparation of substituted N-(1,3,5-triazine-2-yl)aminocarbonyl-arylsulfonamides General formula

< / BR>
where R1= Cl, COOCH3;

R2= OCH3N(CH3)2;

R3= CH3, ON=C(CH3)2, ON=C(CH3)C2H5;

R4= H, CH3,

used in agriculture as herbicides and plant growth regulators

The invention relates to new derivatives of catechol and their pharmaceutically acceptable salts and esters which are useful as medicaments, antioxidants

The invention relates to new derivatives of sulfamethoxypyrazine and herbicides containing them as active ingredients

The invention relates to a derivative of propionic acid, useful as fungicides, to fungicidal compositions containing them and to methods used to combat fungi, especially fungal infections of plants

The invention relates to organic synthesis and concerns a method for obtaining substituted falicov and heterocyclic falicov General formula

(I) where ring a is selected from the group comprising residues:

a) phenyl,

b) pyridyl,

b) five-membered heteroaromatic ring containing oxygen, sulfur or nitrogen as a heteroatom;

R cyano, formyl, ketonuria group, carboxyl group, which may be in the form of the free acid, ester or salt, carnemolla group or mono - or disubstituted carnemolla group or ring

Z

Y1, Y2and Y3attached to carbon atoms and are independently hydrogen, halogen, hydroxyl, C1-8-alkyl, C2-8-alkenyl,2-8-quinil,1-8-alkoxy, C2-8-alkenylamine,2-8-alkyloxy,1-8-alkylsulfonate, each of which may be substituted by 1 to 6 halogen atoms and conjugated WITH1-8-alkoxyl,2-8-acyl, phenyl WITH1-8-alkoxyl, phenylthio, each of which can be substituted one or three halogen atoms;

Y1and Y2>W3, W4and W5independently is CH, CR3or N;

Z is a bridge consisting of elements selected from the group of methylene, substituted methylene, -C(O)-;

R1and R2each independently hydrogen, halogen, C1-8-alkyl, C1-8-alkoxy, C2-8-alkenylamine,2-8-alkyloxy, each of which may be substituted by 1 to 6 halogen atoms, 5 - or 6-membered heterocycle-C1-8-alkoxy, phenyloxy or phenyl-C1-8-alkoxy, each of which may be substituted by 1-3 substituents selected from halogen or1-8-alkyl; R2WITH1-8-alkyl, phenyl-C1-8-alkoxy or phenyl;

X and Y each independently hydrogen, hydroxyl, halogen, cyano, C1-8-alkyl, C1-8-alkoxy, C1-8-alkoxycarbonyl,2-8-acyloxy, carbamoylated,1-8-alkylthio, phenyloxy, phenyl S, each of which may be substituted by 1-3 halogen atoms, or together they predstavljaet,S,NH,NOR12илиCR13R14;

or X and R together may form a bridge having the formula-C(O)-O - or-C(O)-NR2where the carbonyl is attached to A; with the proviso that when R carboxyl in free ether or salt and X and Y together javlautsa, one of the rings a and b contains a heteroatom

The invention relates to a method for obtaining new pyrimidine derivatives possessing valuable fungicidal properties, which can find application in agriculture

The invention relates to pyrimidine derivative of the General formula I:

where R1- alkyl-(C1-C4), O-alkyl-(C1-C4), halogen;

R2- alkyl-(C1-C4), O-alkyl-(C1-C4);

n = 3-5;

Z = COOH, COO-alkyl-(C1-C4), CONHSO2C6H5with herbicide activity, and to a method of controlling undesirable vegetation by processing them in the locus, namely, that the treatment is carried out pyrimidine derivatives of General formula I:

where R1- alkyl-(C1-C4), O-alkyl-(C1-C4), halogen;

R2- alkyl-(C1-C4), O-alkyl(C1-C4);

n = 3-5;

Z = COOH, COO-alkyl-(C1-C4), CONHSO2C6H5in the amount of 1-10 kg/ha

FIELD: organic chemistry, agriculture.

SUBSTANCE: method involves carrying out a seasonal single treatment of plant leaves with asymmetrical derivative of 4,6-bis-(aryloxy)pyrimidine of the formula: wherein X means chlorine atom (Cl), nitro- or cyano-group. Invention provides enhancing the long-term time of plants protection.

EFFECT: enhanced effectiveness and valuable properties of compounds.

6 cl, 6 tbl

FIELD: organic chemistry, herbicides, agriculture.

SUBSTANCE: invention elates to novel derivatives of uracil of the formula [I] possessing herbicide activity, a herbicide composition based on thereof and to a method for control of weeds. In derivatives of uracil of the formula [I] the group Q-R3 represents a substituted group taken among:

wherein a heterocyclic ring can be substituted with at least a substitute of a single species taken among the group involving halogen atom, (C1-C6)-alkyl-(C1-C6)-alkoxy; Y represents oxygen, sulfur atom, imino-group or (C1-C3)-alkylimino-group; R1 represents (C1-C3)-halogenalkyl; R2 represents (C1-C3)-alkyl; R3 represents OR7, SR8 or N(R9)R10; X1 represents halogen atom, cyano-group, thiocarbamoyl or nitro-group; X2 represents hydrogen or halogen atom wherein each among R7, R8 and R10 represents independently carboxy-(C1-C6)-alkyl and other substitutes given in the invention claim; R9 represents hydrogen atom or (C1-C6)-alkyl. Also, invention relates to intermediate compounds used in preparing uracil derivatives.

EFFECT: improved preparing method, valuable properties of compounds.

40 cl, 16 sch, 12 tbl, 65 ex

FIELD: organic chemistry of heterocyclic compounds, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of pyrimidine of the general formula (I) and their pharmaceutically acceptable acid-additive salts possessing properties of neurokinin-1 (NK) receptors antagonists. In the general formula (I): R1 means lower alkyl, lower alkoxyl, pyridinyl, pyrimidinyl, phenyl, -S-lower alkyl, -S(O2)-lower alkyl, -N(R)-(CH2)n-N(R)2, -O-(CH)n-N(R)2, -N(R)2 or cyclic tertiary amine as a group of the formula: R1 means lower alkyl, lower alkoxyl, pyridinyl, pyrimidinyl, phenyl, -S-lower alkyl, -S(O2)-lower alkyl, -N(R)-(CH2)n-N(R)2, -O-(CH)-N(R)2, -N(R)2 or cyclic tertiary amine of the formula: that can comprise additional heteroatom chosen from atoms N, O or S, and wherein this group can be bound with pyrimidine ring by bridge -O-(CH2)n-; R2 means hydrogen atom, lower alkyl, lower alkoxyl, halogen atom or trifluoromethyl group; R3/R3' mean independently of one another hydrogen atom or lower alkyl; R4 means independently of one another halogen atom, trifluoromethyl group or lower alkoxyl; R means hydrogen atom or lower alkyl; R means independently of one another hydrogen atom or lower alkyl; X means -C(OH)N(R)- or -N(R)C(O)-; Y means -O-; n = 1, 2, 3 or 4; m means 0, 1 or 2. Also, invention relates to a pharmaceutical composition comprising one or some compounds by any claim among claims 1-19 and pharmaceutically acceptable excipients. Proposed compounds can be used in treatment, for example, inflammatory diseases, rheumatic arthritis, asthma, benign prostate hyperplasia, Alzheimer's diseases and others.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

21 cl, 1 tbl, 76 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a novel method that can be used in industry for synthesis of substituted aniline compound represented by the following general formula (6):

wherein in the general formula (6) each R1, R2 and R3 means independently alkyl group, alkoxy-group, alkoxyalkyl group, halogenalkyl group, carboxyl group, alkoxycarbonyl group, alkylcarboxamide group, nitro-group, aryl group, arylalkyl group, aryloxy-group, halogen atom or hydrogen atom; each X and Y means independently hydrogen atom, alkyl group, alkoxy-group, alkoxyalkyl group, halogenalkyl group, carboxyl group, alkoxycarbonyl group or halogen atom. Method involves oxidation of substituted indole compound represented by the following general formula (3):

(wherein values R1, R2, R, X and Y are given above) resulting to opening indole ring to yield acetanilide compound represented by the following general formula (4):

(wherein values R1, R2, R3, X and Y are given above) and Ac means acetyl group, and treatment of this compound by reduction and deacetylation. Also, invention relates to novel intermediate compounds. Proposed compound (6) can be used as intermediate substance for production of chemicals for agriculture and as medicinal agents.

EFFECT: improved method of synthesis.

20 cl, 1 sch, 3 tbl, 31 ex

FIELD: organic chemistry, herbicides, chemical technology.

SUBSTANCE: invention relates to derivatives of substituted sulfonylaminomethylbenzoic acid of the general formula (I): wherein R1 means hydrogen atom (H) or (C1-C8)-alkyl; R2 and R3 mean H; R4 and R5 mean H; R6 means H or (C1-C8)-alkyl; R7 means (C1-C8)-alkyl; R8 is similar or different and means (C1-C4)-alkyl or (C1-C4)-alkoxy-group; n means 0 or 1. Compounds of the formula (I) are intermediate substances in synthesis of biologically active compounds possessing the herbicide activity, in particular, in synthesis of sulfonylureas. Also, invention describes methods for synthesis of compounds of the formula (I) and their derivatives.

EFFECT: improved method of synthesis.

27 cl, 1 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: invention relates to the new method of producing formerly unknown 1-(pyrimidine-2-il)propane-2-on of the general formula wherein R designates every time the C1-C10 alkyl group. The method consists in that the reaction of malone diimidate is carried out with the general formula , wherein R has the above-stated magnitudes, with dikenete of the formula . It is preferable to use malone diimidate (II) produced in situ from is appropriate salt and base. Here, the salt of used malone diimidate (II) is dihydrochloride, and tertiary amine. The preferable malone diimidate of the formula (II) is dimethyl malone diimidate.

EFFECT: new compounds feature useful biological properties.

6 cl, 2 ex

Up!