Method of producing fodder composition

专利摘要:
There is provided a method for enhancing the growth rate of meat-producing animals, improving the efficiency of feed utilization thereby, and or improving the lean meat to fat ratio thereof, which involves, orally or parenterally, administering to said animals a growth-enhancing amount of a phenylethane compound or the acid addition salt thereof.
公开号:SU1416046A3
申请号:SU813328205
申请日:1981-08-24
公开日:1988-08-07
发明作者:Кениг Бейкер Памела；Энн Кернан Джейн
申请人:Американ Цианамид Компани (Фирма)；
IPC主号:

专利说明:

4iik
Od
 CM
FIELD OF THE INVENTION The invention relates to agriculture, in particular to methods for producing fodder compoyedium.
The purpose of the invention is to increase the activity of the composition1; and to reduce fat deposition.
An animal as a growth-promoting substance is administered a compound of structural formula 10
CH-CH-NRaBj R RI
de X - hydrogen, halogen or group
CN; Y is hydrogen, NHCORj or group
NH
five.
Z is hydrogen, halogen, OHCN, CFj,
COOR ,, C, -C4-alkyl; R, is hydrogen, GI-C4-alkyl,
alkenyl or //
RJ - hydrogen, C, -Cb-alksh1, cycloalkyl, dimethylphenethyl, benzyl, Z-phenylpropyl
 hydrogen, OH Rg is hydrogen, C, —C-alkyl; Rg is chlorine, methyl or nitro, and its mixing with nutrients is carried out from the races: 3–200 g per 1 ton.
Example 1. Evaluation of the use of the compounds as accelerators of animal growth.
To test females from the Karvort nursery at the age of 6 weeks, they planted 10 pcs. in a cage placed in air-conditioned room conditions (72-76 F, 22-24 ° C) with automatically regulated illumination of $ 14 h they were under illumination and 10 h without illumination. The basic ration used in these studies, the Purina Laboratory Chow ration, which was supplied as desired, water was optionally supplied in any quantity.
After 13 days, weighed in groups of 10 pieces each. and subjected to arbitrary treatments at different concentrations of the compounds of the indicated general formula in the diet. After another 12 days. the mice were weighed and the experiment was terminated.

0
five
0
five
thirty
35
40 DZ jg
jj
Test data are given in table 1, in which the percentage of weight gain compared with control data. For each trial, different control animals were used. The diet into which accelerated growth compounds were introduced included,%: With protein No less than 23.0 Raw fat Not less than 4.5 Raw fibers Not more than 6.0 - Ash Not more than 9.0
Ingredients of the diet: sleep and bone meal, dried skim milk, wheat seed flour, fish meal, animal liver flour, dried beetroot, crushed extruded grain, oats pounded on cereals, soybean flour, dehydrated alfalfa flour, cane molasses, animal fat, protected by butylhydroxyanisole, vitamin B, j as a feed additive, calcium pantothenate, choline chloride, folic acid, riboflavin feed additive, dried brewer's yeast, thiamine, nicotinic acid, vitamin as a feed additive, D-activated plant sterol, vitamin E as a feed additive, caldate carbonate, secondary acid phosphoric acid calcium, iodinated salt, ferric citrate double salt (3-valent-Hoi o) and ammonium citrate, ferric oxide, manganese oxide, cobalt carbonate, copper oxide, zinc oxide.
Example 2. Evaluation of the tested compounds as products that prevent the formation of fat (study in mice). CFJ 55 day old females were weighed in groups and distributed into cells so as to minimize the weight difference between cells. The cells were treated with mice randomly. Each treatment was reproduced 3 times during the test, i.e. 3 cells were treated, 10 mice in each trial. This test consisted of 10 cells with 10 controls. msh1a1-i in each. The tested drugs were mixed with the diet in the indicated doses. During the 12-day period, food was served and water arbitrarily. During the test period, the scattered food was collected. At the end of the test period, the collected food was weighed and the average food consumption of mice in each cage was determined.
3..14
ke for each treatment. Mice were weighed in groups of 10 pcs. and the average weight gain was determined, and the cervical vertebra was displaced. Each baby has a uterine fatty thickening removed. These fatty thickenings of mice from each cage (including 10 pcs.) Were weighed as a single unit.
The data obtained are presented in Table 2 as a percentage reduction in the weight of the fatty bulge. A decrease in the weight of the fatty thickening of the animal is indicative of a decrease in the total fatty amount of the animal being treated.
Example 3. N-tert-butyl-3,5-dichloro-p-methoxy-4-methyl-aminophenethylamine hydrochloride.
7 g of ot - (tert-butylamino) methyl-3,5-dichloro-4-methylaminobenzyl alcohol in 70 ml of thionyl chloride are introduced under nitrogen (N) and the mixture is stirred for 2 h. Excess chloride is added. the thionyl is distilled off in vacuo and the glassy residual distillation is dissolved in 50 methanol. The solution is stirred for 1.5 hours and evaporated to dryness. The residual evaporation product is dissolved in 100 ml of HjO and extracted twice with 50 ml portions. The aqueous layer was neutralized with solid NaHCOj and extracted. The extract is dried over MgSO4 and evaporated to dryness in vacuo, resulting in 4.1 g of a semi-solid product, which, after mixing with ethyl ether, forms 1.07 g of the final compound T.Sh1. 220-22GS.
Similarly, receive the following ethers:
C1

CHsNH
CH-CH2-NH-Bu- ±
O-RI
Alcohol: Ethanol
R
,
1-SzN ,. 2-СзН7,, з
Benzyl
0
five
0
Allyl
alcohol
4-methoxybenzyl alcohol
4-Chlorobenzyl alcohol
4-Nitrobenzyl alcohol
4-Methylbenzyl alcohol
3,4-Dimethylbenzyl alcohol
3,4-Dimethoxybenzyl alcohol
3,4-Dichlorobenzyl alcohol
2-Chlorobenzyl
alcohol
2-Methylbenyl
alcohol
Example 4. Carrying out the process as in example 3, get the following ethers by replacing methanol-5 la corresponding alcohols:
Allyl
4-Methoxybenzyl 4-Chorbenzyl 4-Nitrobenzyl 4-Methylbenzyl
3,4-Dimetsh1benzyl 3,4-Dimethoxy-benzyl
3,4-Dichlorobenzyl 2-Chlorbeisyl 2-Metsh1benzyl
R
CH-CH2-NH-C (CH3) s OR
M.p.
Benzyl190-193
Allyl57-59
4-Methoxybenzyl 4-Hggorbenzyl 4-Nitrobenzyl 4-Methylbenzyl 3,4-Dimethylbenzyl 3,4-Dimethoxybenzyl 3,4-Dichlorobenzyl Phenyl Oil
4-Chlorophenyl 4-Methoxyphenyl 4-Methylphenyl 2-Chlorophenyl 4-Nitr of NILE Example 5. N-Tpetbootsh-3-chloro-5-cyano-y-methoxy-4-aminophenylamino hydrochloride.
Carrying out the process as in Example 3, C (tert-butylamino) methyl-4a cherno-3-chloro-5-1 w-benzylic acid is converted into the final compound and, similarly, the following compounds are obtained:
Ar-CH-CH-NH-R-HCl AXIS,
Ar
R
tert-butyl
tert-Vutyl Isopropyl
tert-butyl tert-butyl
tert-butyl tert-butyl tert-butyl tert-butyl
tert-butyl tert-butyl
tert-butyl
4-Amico-3, 5-dicyano
phenyl
4-amino-3-chloro-5 trifluoromethyl phenyl
4-amino-3-chloro 5 trifluoromethylphenyl
4-Acetamido-3, 5 dichlorophenyl.
4-acetamidophenyl
4-amino-3-chloro-5HjN-CO-phenyl
4-amino-3-chloro-5NO-CO-phenyl
4-amino-3-chloro-5methylphenyl
4-amino-3-chloro-5methoxyphenyl
4-amino-3-chloro-5 nitrophenyl
4-amino-3-chloro-5 CHjO-0-CO-phenyl
4-amino-3-chloro-5 dimethylaminomethylphenyl
4-amino-3-cyanophenyl tert-butyl
Example 6, 5- (4-Amino-3,5-dichlorophenyl) -3-tert-butyl-2-oxazolidinone.
0.5 g of 4-amino-o6 (tert-butyl but no) methyl-3,5-dichlorobenzyl alcohol in 10 MP, mixed with 1 ml of EtjN (Et - ethyl) at a temperature and 2 MP of 12.5% -gr COQl in binzole / 5 MP CHjCl is added over 15 minutes. The resulting suspension is stirred for 20 minutes at 1 ° C and heated to room temperature while stirring for 1.5 hours. The mixture is evaporated to dryness and the residue evaporated is subjected to chromatographic separation on silica gel, eluted with hexane / CH2C12 in a ratio of 1: 1, resulting in 0.1 g of oil, which crystallizes to form the final compound, 97-103 ° C.
When carrying out the process in the same way, ni- | (allylamino) methyl-4-amino-3,5-dichlorobenzyl alcohol chemically interacts with phosgene, resulting in 5- (4-amino-3,5-dich1urphenip) 3-allyl- d - oxazolidinone.
Having carried out the process in a similar way, the following is obtained:
AR-CH-CH2
0 N-RS
From 3
and
0
five
0
five
0
five
0
five
0
five
Ag
3 3 5-Lichlorophenyl
R,
tert-butyl tert-butyl tert-butyl
3,5-Lichlorophenyl
4-Acetamidophenyl
4-amino-3-chloro. P-5 cyanophenyl tert-butyl
4-amino-3-chloro-5 trifluoromethylphenyl tert-butyl
Z-Chloro-4-acetamidophenyl tert-Butyl
3,5-Dichloro-4-methylaminophenyl tert-Butyl
3,5-Dichloro-4-ethylaminophenyl tert-Butyl
3,5-Dichloro-4-isopro
pylaminophenyl tert-butyl
 3,5-Dichloro-4-acetamidophenyl tert-Butyl
3,5-Dichloro-4-methoxycarbonylaminophenyl tert-butyl
3,5-Dichloro 4-benzyloxycarbonylaminophenyl tert-Butyl
3,5-Dichlorop-4-methyl-carbamate aminophenyl tert-butyl
4-amino-3-chloro-5-methylphenyl. tert-butyl
4-Amino-3-cyanofensh1 tert-Butyl
4-amino-3-trifluoromethylphenyl tert-butyl
4-Amino-3-chloro-5NH CO-phenyl tert-Butyl
4-amino-3-chloro-5HOOC-phenyl tert-Butyl.
4-Amino-3-chloro-5CH OOS-phenyl-tert-Butyl
4-Amino-3-chloro-5 (CE / ECH-Ft-Butyl
4-amino-3, 5-dicyanophenyl tert-butyl
Example 7. Acetate 4-amino-vi-. (Tert-butylamino) methyl-3,5-dichlorobenzyl alcohol.
The mixture containing 1 g of 4-amino-o-1 (tert-butyl amino) methyl) -3,5-dichlorobenzene alcohol is stirred in 35 ml at TeMnepaTyii 10-15 ° C and added to the mixture dropwise. 0.37 g (Ac - acetyl) and 0.5 ml EtjN. Then the reaction mixture is heated to room temperature and
71416046
subjected to thin layer chromatographic separation. The mixture was evaporated to dryness in vacuo and the resulting yellow. the viscous liquid (1.5 g) is mixed with 50 MP of ethyl ether, as a result of which a yellow solid Ve-, creeps; ectr (0.84 g) with t; pl. . This compound, as determined by NMR spectra and the neutralization by the sclerae, is a salt of acetic acid. When processing 100 mg of this salt in 30 ml of 30 ml of a 10% aqueous solution of NaOH, it is neutralized. The solution is dried with MgSO4 and evaporated to dryness in vacuo, resulting in a viscous final compound.
Found,% g C 52.38; H 6.51, 20 N 8.88.
Calculated,%: C 52.67; H 6.32; N 8.78. In the same way, propioic anhydride, butyric anhydride, pivalic anhydride, and benzoic anhydride are chemically reacted with 4-amino-01. (Tert-butshtmino) methyl 2.-3. 5-dichlorobenzyl alcohol (A) and oi - (t-butylamino) methyl-3,5-dichloro-4-methylaminobenzyl alcohol (B), resulting in propkonat5 butyrate, pivalate and benzoates of compounds A and B,
Example 8. According to the method described in Example 7 using the corresponding acid anhydride, the esters are obtained as follows:
thirty
35 but bu
od- hl 40 di lot i. one day 45. CH NaO hour CH Soi 50 vayu vayu 2.6 2.6 126
i RgBgN
6
H
H
H
H
H
H
SNS
H
H
H
CH,
C, H,
,
, CH,
sn.
AR-CH-CH2-MN-S (CH3) 5
i-c-Be
ABOUT
 . ,; 15
0
five
Ag
3,5-Lichlorophenyl 4-amino-3-chloro-5-cyanophenyl
4-amino-3-chloro-5-trifluoromethylphenyl
4-amino-3-chloro-5-H NCO-phenyl
4-amino-3-chloro-5-HOOC-phenyl
4-amino-3-chloro-5-methyl-phenyl
4-amino-3-bromo-5-cyanophenyl
4-amino-3-chloro-5-CH, OCO-phenyl
CH,
CH, CHj-CH3 CH, CH CH,
4-amino-3-chloro-5-0 (CH5) -CH-phenylCE,
4-Amino-3, 3-dicyanophenyl CH3
4-amino-3-1scanophenyl tert-C NPrimer 9. N- (4-amn-5 but-3,5-dichloro-o-oxyphenethyl) -N-tert-butylacetamide acetate,
A mixture containing 2.5 g of 4-amine 6-od-C (tert-butylamino) methyl-3,5-dichlorobenzyl alcohol, 25 mp pyridine and 10 ml of acetic anhydride, is stirred for 3 hours. and exhale dry in vacuum with heating to 70 ° C. The residual product was treated with ice, .100 mp 5. and 50 ml of 10% NaOH solution. The phase is separated and the aqueous portion is further extracted (twice in 50 ml portions). The combined solutions are dried; 0 is watered (by) and evaporated to dryness, as a result of which a solid product is obtained, which is washed with hexane and recovered. 2.61 g of the final compound, -; etc. are obtained. 126-13b with
Carrying out the process in the same way, using the corresponding acid anhydrides, the following compounds are obtained:
five
Cl
CH-CH2-K-С1СНз) з
II
O-CORE GORg

R, CH,
C, H5
2-C, H,
HC, H,
CH,
CH, 0-CO
CH, NH-GO
CHjCO
CH,
R.
CHj CH, CH, CH, CHZ CHZ CH, CH,,
HC, H,
-CH2-M-С (СНз) from CORe SOBb
Rg
3,5-di
3-chloro-tert-inomethyl
3-chloro-5-СНДООС-
3-chloro-5-me
orphenyl
3-chloro-5-cyano
3-chloro-5-trifluoryl
3-hlop-5-H2, NCO-
s.n
sn.
.s, n.
SNZ SI,
SI,
sn.
CH,
Example 10 Acetate 4-acetates-to-° C- (tert-butylamino) methyl-3,5-dichlorobenzyl alcohol;
1.57 g of 4-acetamido-Y- (tert-butyl-45 amino) methyl-3,5-dichlorobenzyl alcohol is suspended and stirred in 15 sludge while adding 1.2 g of triethylamine in 30 ml, after which 0, 7 g of acetic anhydride in 15 ml. The mixture is stirred for 20 h and then washed with 100 mp of NaOH solution. The organic phase is separated.
12.97 g of C - (- tert-butylamino) methyl-p-nitrobenzyl alcohol is dissolved in 270 MP, the Solution is cooled to -5 ° C, and 54 ml of 12.5% phosgene in benzene is slowly added. After stopping the addition, the mixture is stirred for 3.5 hours and poured into ice. The organic phase is separated and the aqueous layer is extracted (twice in 100 ml portions). The combined organic layers are washed and saturated with a solution of NaHCO (twice in 250 ml),
100 ml and dry over MgSO4. The solution is evaporated to dryness, resulting in 16.3 g of product, which is recrystallized from 50 MeOH (methyl alcohol). 12.58 g of 3-tert-butyl-5-p-nitrophenyl) -2-oxazolidinone are obtained. , mp.123-125 ° C. This product (10 g) is dissolved in 200 MP of MeOH and is subjected to hydrogenation, dried (by means) 56 tion over Rene nickel under pressure and evaporated to dryness in vacuo. Osta-51 paig (3.57 kg / cm) at 40 s. The post-evaporation product is dissolved in the filtration and evaporation is obtained in 30 MP of ethanol and H, 0 is added to 8.21 tons of 5- (p-aminophenyl) - tert-butyl small amounts, followed by 2-oxazolidinone, mp, 123-129 ° C,
1604610
10% HC1 is added for acidification. | The mixture is evaporated to dryness in vacuo, and the evaporation residue is crystallized from acetone / hexane (30 ml / 5 mp). The result is 1.35 g of the final compound, m.p. 254-257 p.
Carried out a process similar
10, but using instead of acetic anhydride, propionic acid anhydride, butyric anhydride, pivalic anhydride and benzoic anhydride, the corresponding propionate esters, butyrate, pivalate and benzoate are obtained.
Example 11. Acetate ci .- (tert-butylamino) methyl-m-hydroxybenzyl alcohol,
20 In the same manner as in Example 10, m- (benzyloxy) -o {, - (tert-butn-amino) methyl benzyl alcohol is converted to m- (benzyloxy) -o6- (tert-butylamino) methyl benzyl acetate
2B alcohol. This product is then debenzylated, resulting in oi - (tert-butylamino) -methyl-m-hydroxybenzyl alcohol acetate.
Example 12, 5- (p-Aminophenyl) - 3-tert-butyl-2-oxazolidinone,
12.97Go - (- tert-butylamino) methyl-p-nitrobenzyl alcohol is dissolved in 270 MP, the Solution is cooled to -5 ° C, and 54 ml of 12.5% phosgene in benzene is slowly added. After stopping the addition, the mixture is stirred for 3.5 hours and poured into ice. The organic phase is separated and the aqueous layer is extracted (twice in 100 ml portions). The combined organic layers are washed and saturated with a solution of NaHCO (twice in 250 ml),
45
100 ml and dry over MgSO4. The solution is evaporated to dryness, resulting in 16.3 g of product, which is recrystallized from 50 MeOH (methyl alcohol). 12.58 g of 3-tert-butyl-5-p-nitrophenyl) -2-oxazolidinone are obtained. , mp.123-125 ° C. This product (Yu g) is dissolved in 200 MP MeOH and subjected to hydrogenogenization1114
Example 13, oi - (tert-Butyl-amino) -methyl -3,5-dichloro-4-dimethyl-aminobenzyl alcohol.
A mixture containing 50 g of p-fluoroacetate phenone and 150 ml of a 40% aqueous solution of dimethylamine is heated under pressure in a flask at 90-100 ° C. After 2 hours, a pale yellow oil is formed. The mixture is cooled and the oil is cured. The solid product is recovered and thoroughly washed from water, with the result that after recrystallization from heptane, 54.93 g of p-dimethylaminoacetophenone are obtained, pcs. 101-103 A portion of 72 g of acetophenone is heated from 129 g of N-chlorosuccinimide in 700 ml of toluene to reflux temperature and maintained at this temperature for 35 minutes. The mixture is cooled and filtered. The pressed precipitate is washed with 200 ml of toluene,,; the filtrate and the washing solution were combined to dryness in vacuo, resulting in 66 g of oil. This oil is subjected to chromatographic separation on SiO using a mixture of 40% hexane / eluted. .. to give 38.9 3,5-dichloro-4-dimethylaminoacetophenone in the yellow oil. A portion of this oil in the amount of 5.22 g is added in separate parts to 2.75 g of SeOg in 20 MP dioxane and O, 7 ml at 55-60 ° C. This mixture is heated at reflux for 4.5 hours, cooled and filtered through siliceous earth. Squeeze the precipitate washed with 20 ml of dioxane. The dioxane solutions are cooled to 15 ° C, 2.11 g of tert-butylamine is added dropwise to them, resulting in a precipitate of tan color. After stirring for 15 minutes at room temperature, the mixture was diluted with 200 ml of ethanol, cooled to 5 seconds, and 7 g of NaBH was added in separate portions. After 15 hours, the sies process 300-400 g of ice and 200 mp of water at a temperature below 10 s. The mixture was stirred to dissolve all solids and extracted with 300 mp. The layer was washed with 100 mi of water, dried (over MgSO4) and evaporated to dryness in vacuo, resulting in 5.6 g of orange oil. This oil is dissolved in ethyl ether, the active 066 is decolorized.
coal and evaporated to a volume of 15 ml. After cooling, a crystalline product is obtained. Finite
the product is recovered in the form of white crystals, mp, 96-99 ° C.
Example 14 of 5- (4-lmino-3,5-dibromophenyl) -3-tert-butyloxazolidine. A mixture containing 2 g-4-amino0 of 3,5-dibromo-c - (tert-butylamino) methyl benzyl alcohol and 5 ml of a 37% formalin solution in 20 mp of toluene containing several paratoluene sulfonic acid crystals is heated
5 under reflux at a constant boiling water temperature. After heating for 3 hours, the mixture is cooled, diluted to 75 ml and washed with 10% aqueous
0N NaOH solution (twice in 20 ml portions). The aqueous portion is then extracted with 10 ml of CHgCl2, the combined organic extracts are dried over MgSO4 and evaporated to dryness in vacuo, resulting in 1.6 g of a clear brown oil. . Mass spectrographic analysis (chemical ionization method) shows the mass + H 377, which corresponds to
0 this connection. The proton NMR spectrum shows a singlet at 4.53 in CBC1 3, which indicates the presence of a group in the final compound.
Carried out a process similar
g, but using the corresponding arylate} {olamines instead of 4-amino-3, 5-dibromo-o /, - (tert-butylamino) methyl benzyl alcohol, the corresponding oxazolidines are obtained:
0 AP-CH-CH2
(SNS) 5
45 where Ar is 4-amino-3,5-dichlorophenyl, 4-methylamino-3, 5-dichlorophenyl, 4-amino-3-chloro-5-cyanophenyl, 4-amino-3-, chloro-5-trifluoromethylphenyl , 4-amino-3-chloro-5-methylphenyl, 4-amino-3-bromo,.-Phenyl, 4-amino-3-bromo-5-HOOC-phenesht, 4-acetamido-3, 5-dichlorophenyl, 3, 5-dichloro-4-methoxycarbonyl-aminophenyl, 3,5-dichloro-4-methylcar-, bamoyl 1inophenyl, 4-amino-3-cyano-55 phenyl, 4-amino-3-trifluoromethylphenyl, 4-amino-3, 5-dicyanophenyl .
Example 15 4-Benzylamino-od- (tert-butylamino) methyl 3,5-dichlorobenzyl alcohol.
1314
Oops (the process is the same o6 times as in example 13, the indicated compound is obtained, mp 86-89 C „Example 16. (tert-By-) -1-oxyethyl -2, b - dichlorobenanilide.
A mixture containing 2.04 g of 4-amino-3.5 dichloroacetophenone and 0.25 ml of three ethylamine in 10 ml of benzoyl chloride is stirred and heated at 130-135 ° C for 2 hours. This mixture is cooled, filtered and the product is washed with ether-Mo Amide and is further oxidized with SeOj in the same manner as in Example 13, resulting in a final compound, mp 177-182 ° C.
Example 17, (x: (tert-Butyl-amino) methyl-3,5-dichloro-4-methylamino-benzyl alcohol,
p-Methylamino acetophenone is prepared and chlorinated, resulting in 3,5-dichloro-4-methylamino-acetophenone. This canon (18 g) is stirred in 200, and 4.65 mp is added dropwise to 50 ml of CHCl ,. Ios: After stopping the addition, the mixture over-: meats up for an additional 20 minutes and heated at reflux for 25 minutes. The mixture is cooled by the addition of 100 ml and a saturated solution is carefully injected in the solution until the mixture becomes neutral. The CHCl layer is separated and the aqueous layer is further extracted with 100 ml of CH. Clj. The combined extracts are dried (over MgSO4) and evaporated to dryness, resulting in 16.3 g of phenacyl bromide. This material (16 g) is stirred at 12–15 ° C in 80 MP of ethanol and 40 mt tert-butylamine is added dropwise. After the addition is stopped, the mixtures are stirred for 10 minutes at 12–15 ° C and then cooled to 5 ° C and 4 g of NaBH4 are carefully added. After stirring for 0.5 hours, the mixture is warmed to room temperature and stirring is continued for 0.75 hours. The mixture is poured into 300 ml of ice with stirring and the resulting mixture is extracted with 300 mp. The CHjCl extract is dried (over MgSO4) and evaporated to dryness in vacuo, resulting in a yellow oil. After stirring this residual product, evaporation with these
614
7.45 g of the final compound (after recrystallization 1a; s from ethyl alcohol) is obtained by lithium ether; mp, 9B-10GS,
Example 18. (tert-Butyl-ino) -oxyethyl anthramine 1-ylonitrile,
The mixture containing 48.86 g of p-acetone-acetophenone is stirred in 490 ml of toluene and at the same time 64.5 g of N-bromo succinimide is added in separate portions for 0.5 h at a temperature below 40 ° C. After 15 minutes water wash mix (4x
xyou ml). The solution is dried (over
MgSO4) and dry until a yield of 70.53 g of 4-amino-3-bromadetophenone, t, pl. 59-62 C. Portion of this product in the amount of
35 g in 180 to dry dimethylformamide is stirred and heated at reflux with 17.57 g for 6 hours under N atmosphere. Then 180 ml of solution is added.
/ DS1 (40 g FeCly-mp concentrated HC1 / 60 ml), and the mixture is heated for 20 minutes at 60-70 ° C and poured into 350 ml of water. The aqueous mixture is extracted ij extracts
washed with water, with a saturated NaHCOJ solution with water. The solution is evaporated to dryness in vacuo and the evaporation residue is recrystallized from 95% ethanol,
resulting in 1.4; 25 g of 4-amino-3-cyanoacetophenone 5 m.p. 155-159 C. Porschchu this product in the amount of 458 g in 100 mp EtOAc (Et-ethyl Ac - acetyl) and 100 mp CHCl,
containing 13.32 g of CuBr, is heated with reflux for 20 minutes. After the addition of 20 ml of EtOH, the mixture is further heated and after that they are fired, hot NIN. The filter cake is removed | wash with 50 ml of hot MeOH / CH C mixture (MeOH-methyl alcohol) and the combined organic solutions are evaporated to dryness in vacuo. Residual product
evaporation was stirred in 25 ml and the solid was recovered and washed with CH2C12.S, resulting in 85.08 g of phenacyl bromide. This product is added to 50 mp of tert BuNHj (Bu-butyl) in 100 ml of EtOH
at 5 ° C in an atmosphere of N,. After stirring for 10 minutes, the mixture is heated to 30 ° C, resulting in a solution. This solution is cooled.
is given up to 10 ° C and NaBH is added in separate portions. After 45 minutes, the mixture is heated (to 42 ° C) and held at 20 ° C until the isotherm decreases. The mixture is then evaporated to dryness and the residual product is washed. This residual evaporation product is dried and treated with 200 MP of boiling MeOH and a hot solution of MeOH Lilted. The filtered filter cake is further washed with hot MeOH and the combined filtrates are concentrated, resulting in a crystalline product. This solid was recrystallized from MeOH / 2-ErOH (PrOH-propyl alcohol), resulting in 2.08 g of the final compound, m.p. 184-186 ° C.
Similarly, the following related compounds are prepared using acetophenone as the starting material of the corresponding product:
Rgbgn
CH-CHg-NHEg
he
R,
n
CHj SNS
R:
,
tert-Butyl tert-Butyl tert-Butyl n-C H tert-Butyl 2-C H-, tert-Butyl n-C ((H tert-Butyl CHj 2-C, H7
tert-butyl
X
N N N N N N
n n n

Benzyl
CjHj-tert-Butyl C1 n-C H tert-Butyl C1 n-CsN, tert-Butyl C1 19. 3-Chloro-5-2-. but) -1-hydroxyethyl
o-Z-cyanoacetophenone ol is heated at the reflux rate for g of N-chlorosuccinimide, t, and filtered. The filtrate is heated at a temperature for 2 hours. washed and washed with water. The product processed GC4 / 14 ml of CHCI3, addition of HCl, and 4.9 MP of EtOH.
The mixture was dried to dryness and the evaporation residue was suspended with, removed and washed, yielding 2.84 g of phenacyl bromide. This product chemically reacts with TpeT-BuNHxj and is reduced to NaBH. by performing the process described in Example 18, resulting in a final compound, mp. 128-138 ° C.
Carrying out the process in the same way, the following compounds are obtained:
Fg-EgN
20
CH-CH2-NH-R3 OH

thirty
35
25
8 N
n
CH:
H
n
RC
R
H
sn
sn,
n n
40
2-Propyl tert-Butyl tert-Butyl tert-Butyl
2-11propyl tert-butyl n-butyl tert-butyl benzyl tert-butyl
Example 20. (tert-Butylamino) -1-hydroxyethyl-3-chloroanthranilic acid hydrochloride.
A mixture containing 1.36 g of (tert-butylamino) -1-hydroxyethyl-3-chloroanthranilonitrile in 21 mp of 50% aqueous NaOH and 21 ml of EtOH was stirred under an atmosphere of N for 0.5 h. in order to remove EtOH and acidify to pH 3, the mixture is then evaporated to dryness in vacuo. The residual product is treated several times with methyl alcohol and ironed out. The solid product is then treated with a solution which is prepared from 40 ml of MeOH and 2 ml of acetyl chloride. After standing overnight, the mixture is filtered and the filtrate is evaporated to dryness. The screening cake was also washed with methyl alcohol (MeOH) and added to the filtrate obtained earlier. The precipitate is dissolved in acetone, filtered and quenched to dryness. The solid was stirred with EtO and filtered to give 1.49 g of the final compound, mp 95-115 s.
50
55
2- (tert-butylamino) -1-hydroxyethyl benzene, 0.8 g of the final compound.
t "PL i.J
Similarly, the following compounds are obtained:
GOOH
zamid
A mixture containing 1.02 g of 3-bromo-5- 2- (tert-butylamino) -1-hydroxyethyl anthrononitrile in 25 ml, 5 ml of 50% NaOH solution and 30 ml of EtOH. stirred and heated at 55-65 ° C under N atmosphere for 1.25 hours. This mixture is RgRgN
Scrub, remove EtOH, extract with GHC1, wash with 25 NP of 2% NaOH, dry (over MgSO4 (}) H and evaporate 35 to dryness, resulting in 0.74 g of product. This solid is stirred with pentane and filtered, as a result what is obtained is 0.6 g NN CHj
Negative desired compound. 135-145 ° C.
The following compounds are prepared in a similar manner:
CONHg
СН СН2- Н-С1СНз) з
he
,
sn,
CJ hsns
2-C H
, SI,
X
CI C1 C1 C1 C1 C1 C1
GOOH
8 N N CHj
n n n n n
,
Example 23. 5- (3-Hydroxyphenyl) - 3-tert-butyl-2-oxazolidinone,
As described in Example 8, (m-benzyloxy) -o1- (tert-butylamino) methyl benzyl alcohol is converted to the oxazolidinone compound by treatment with phosgene. Then, nucleation is debenzylation, resulting in the final compound.
Example 24. 5- (3-hydroxyphenyl) - 3 tert-butyloxazolidine,
As described in Example 12, m- (benzyloxy) (tert-butshtamino) methylZ
1914
Benzyl alcohol chemically interacts with formaldehyde, resulting in an oxazolidine derivative, which is debenzylated in the manner described in Example 10, resulting in the formation of the final compound.
Example 25. 4-Ami-Ho-N-tert-Butyl.-3,5-dichloro-B- (methylthio) -phenethylamine Hporohydrate.
As described in Example 3, N-tert-butyl-3, 5-dichloro-chloro-4-aminophenethylamine hydrochloride is obtained. A portion of this product in the amount of 11 g is added in separate portions to 5 ml of methyl mercaptan per 100 ml.
ml of dry ethylene Q
chloride at a temperature of from -10. do O

Cess as described in the application of the corresponding compounds instead of chl Ktret-4butyl-3,5-dichlorophenethylamine and adding mercaptans to obtain simple thioethers:
Ar-CH-CH, -NH-R, + RSHh
Ar
R
The mixture was stirred and gradually brought to room temperature over time. Q 4 days. The mixture is filtered, the filter cake is washed with ethylene dichloride (500 mp, twice). The solid product is dispersed in 200 mp.
water, cooled to 5 ° C and alkalinized - 25 4-amino-3-cyanoate .6 n. NaOH solution, resulting in phenyl. A methyl of which produces a white oil, which. 4-Methylamino-3, 5- was extracted (three times, p-dichlorophenyl, Methyl and 100 np each). The extract is 4-amino-3-chloro-dried (over MgSO4) and 5-trifluoromethyl methyl is evaporated.
dry, resulting in 6.41 g of dark green oil. This oil is stirred in a mixture of HC1-isopropanol and the mixture is vortexed dry. The evaporation residue is stirred in 35 ml of ethyl ether for 16 hours and filtered, giving 3.63 g of solid product, mp. (with decomposition) 178-181 ° C. This solid product is heated at reflux temperature of ethyl acetate and filtered to give 2.07 g of product with m.p. 19b with
The final compound is also prepared by introducing a 5-10 fold excess amount of mercaptide into tetra--. hydrofuran at 0-10 ° C and the subsequent treatment above.
Example 26 By carrying out the process as described in Example 25, the following ethers are prepared by: using appropriate mercapes
tans instead of methyl mercaptan: CV
NgK
CH-CHj-NH-Bj SR-HCl 20
R
R.
Methyl
Ethyl
2-Propyl
n-butyl
tert-butyl
n-hexyl
Phenyl
Benzyl
Example 27
cess as described in example 25, but the use of the corresponding chlorine-containing compounds instead of ctret-4-butyl-3,5-dichloro-hydrochloride | -chloro-4-am nofenethylamine and adding the corresponding mercaptans, the following thioethers are obtained:
2-Propyl
tert-butyl
tert-butyl
tert-butyl
tert-butyl
tert-butyl
tert-butyl
2-Propyl
Carried proAg-CH-CH, -NH-R, + RSHAr-CH-CH, -NHR,
h
SR
Ar
R
R:
5 4-amino-3-cyanophenyl. Methyl. 4-methylamino-3, 5-dichlorophenyl methyl 4-amino-3-chloro-o 5-trifluoromethyl methyl
d
4-amino-3-chloro-5-cyanophenyl 4-amnno-3-chloro-5-cyanophenyl with -Acetamido-3, 5-dichlorophenyl 4-amino-3-chloro-5H, H 2 O phenyl
Methyl
Methyl
Methyl
Methyl
2-Propyl
tert-butyl
tert-butyl
tert-butyl
tert-butyl
tert-butyl
tert-butyl
tert-butyl
tert-butyl
tert-butyl
tert-butyl
4-Amino-3-chloro-0 5-HOCO-phenylmethyl
4-Amino-3-chloro-5-methylfensh1Etil
4-amino-3-chloro-5-methoxyphenyln-butyl
4-amino-3-chloro-5-nitrophenylmethyl
4-Amino-3-chloro-5-CH O-CO-phenyl Methyl tert-Butyl
Example 28. 3,5-Lix-4- (N, N-diethylamino) acetophonone
4-Amino-3, 5-dichloroacetophenone (2.5 g) in 10 MP of acetic anhydride and 25 ml of pyridine are stirred and heated at reflux for 20 hours. The mixture is evaporated to dryness and the residual product is treated with ice and 10% NaOH solution and extracted with CH2Cl2 (three times in 50 ml portions)
0
five
2114
The extracts were precipitated out () and evaporated to dryness, whereby 2.42 g of a semi-solid were obtained, which was purified by chromatography using SiO and as an eluent, to give 1.06 g of 4- (H, H-diacetylamino) 3 , 5-dichloroacetophenone as an oil. This product was dissolved in 10 Nl of tetrahydrofuran (THF) under a nitrogen atmosphere and 18 ml of 1 M THF was added dropwise. The mixture was stirred until the reaction was stopped and water was carefully introduced. The mixture is evaporated to remove tetrahydrofuran and 20 mp H of 20 and 10 ml of 10% NaOH are added. The aqueous mixture is extracted with CHjCl2 (three times in 25 ml portions), the extracts are dried (over Na.SO4) and evaporated to dryness, resulting in 0.68 g of the desired alcohol. This product (0.3 g) in 2 ml was added to 0.32 g of pyridine chloroformate (PCC) in 2 ml of CHgCl. After 1.25 hours, an additional 0.3 g of pyridine chloroformate was added, after 0.5 h the solution decanted and the precipitate washed with 10 ml. The combined solutions were diluted with 50 ml, washed with 10 ml of a saturated solution and 10 ml of H2O and dried over Na. The solution is evaporated to dryness, as a result of which a residue is obtained, which is subjected to chromatographic separation on SiO using as eluent. As a result, 0.02 g of the final compound is obtained as an oil.
Spectrum HN # (CDC1,) 5; 1.0 (6H, triplet); 2.5 (SA, singlet); 3.25 (4H, quartet); 7.83 (2H, singlet).
As the second component, monoethylaminoacetophenone is obtained as a solid (0.12 g).
The 3,5-dichloroethylaminoacetophenone is then chemically reacted with propionic anhydride, reduced and reoxidized in this way, resulting in 3,5-dichloropropane-N-ethyl-N-phropyl-aminocaphosphonone.
In a similar manner, the following 4- (N, N-dialkylamino) -acetophonones are obtained, which are necessary for the preparation of 4- (H, M-disubstituted amino) compounds of general formula (I)
6046
 -O CO-CH3
Y
R.
R,
X
8 H-CjHj H-C, Hf Cl
ns, N, Cl
Y cl
C, H,
C, H
c.H
CjHf C, H5
Cl
, Cl Cl Cl CH, Cl CF, CjHj Cl NOj 5 Cl Br
  Cl OCHj Example 29. oi - (tert-Butyl-amino) methylC-3,5-dichloro-4-diethylaminobenzoyl alcohol.
0 In the same manner as in Example 13, 355-dichloro-4-diethylaminoacetophenone is oxidized by SeOj, and reductive alkylation with a tert-VishH / NaVN mixture, resulting in the final compound, m.p. 96 ° C.
Similarly, oi - (tert-butylamino) methyl-3s 5-dichloro-4- is obtained. (n dipropyl) aminobenzyl alcohol. 0 Example 30. 2-Bromo 3, 5-dichloro-4-diallylaminoacetophenone and 4- (allylamino) -2-bromo-3, 5-dichloroethane-phenone.
V
CL
V-v
(CH2 CHCH2) 2N nQ-CO-SNgVg
Cl
45
СН2 СНСН2-Ь1Н CI
VCO-CHoBr
Triethylamine (17.0 g, 0.168 mol) is introduced in one portion into allyl D105.9 g bromide, 0.875 mol) under nitrogen atmosphere, the resulting white solution
gives an exothermic reaction, heated to 70 ° C, and converted to a dense solid white mass for 5 minutes. The solution formed by adding 100 ml of dimethylformamide is stirred for 1 hour at 70-95 C. To it is added a solution of 4 - amino-2-bromo-3, 5-dichloroacetophenone (25.0 g 0.088 mol) in 50 ml dimethylformagda in the form of one portion, and semi-chlorobenzyl alcohol of the formula
231416046 24.
The resulting reaction mixture is brown. The mass spectrum of chemical ionization of color is maintained at 80-90 ° C for (M + H) 332.
2 hours. The progress of the reaction is very Example 31, 4- (Allylamino) - often limited by means of ton- (tert-butylamino) methyl-3,5-layer chromatography (using SiOj as an adsorbent and a mixture of CH2C1 ./hexane 1 : 1 as eluent), since prolonged heating results in the decomposition of both the starting material and the reaction products. The reaction mixture is poured into 1.5 liters of water and stirred for 0.5 hours. After the second mixing with water, residual floor (15.8.92 mol) in 10 ml is added dropwise a brown solid in 1 liter for 1 hour. stirred with 150 ml of CCl for a solution of tert-butylamine (1.34 g 0.5 h before forming a suspension. Yellowish-brown solids are removed by filtration and dried by 20 ° by cooling in a bath; with a mixture of dry ice - CC. 14.9 g (59.6%) of phenacyl methyl bromide are formed The CC14 filtrate is mixed with MgSO ;, filtered, and concentrated, resulting in a half-25 for 1.5 hours. Cyanol is added: 9.42 g of sodium syrup-like syrupy liquid (2.80 g, 44.6 mmol) Brown color.
When performing gradient elution chromatography with appearance. (hexane / СНгС1г 10 / 0-8 / 2) in a column (22.8-5.08 cm) with silica gel 60 receive two main fractions,
A. 1.82 g (5.7%) of the yellow most flowing syrup is identified as 2-bromo-3, 5-dichloro-4-diallylamino-acetophenone.
IR (net): 1680.
NMR spectrum (CDC1,) 5; 7.93 (singlet, 2, AR-H) j 6.25-5.55 (complex multiplet, 2 CH) J 5.40-4.95 (complex multiplet, 4, CH), 4.40 ( singlet, 2,), 3.87 (multic1
CHg-CHCHjNH-Q-CHCHj-Nvic (CHj), CI HE
Solution-4- (allylamino) -2-bromo-3, 5-dichloroacetophenone (2.88 g
18.3 mmol) in 20 ml of tetrahydrofuran. The temperature of the reaction is maintained from
My yellow suspension is heated to
room temperature for
30 min and stirred at 21–22 ° C.
in two portions e for 5 minutes, resulting in a thick, tan-brown suspension with ssuat-o.
tiplet similar to doublet, Hz,),
30 to 22-25 ° C. Glacial acetic acid (ml) is added dropwise to form a yellow solution, which is stirred at room temperature for 3 days. The reaction mixture is poured into a solution of 100 ml of water and 100 ml of a saturated aqueous solution of NaCl, the pH value of which is then adjusted to 7 with 10%, and extracted three times with Et, jO. The combined extracts are shaken with two portions of dilute aqueous HC1 which are combined, neutralized with 10%, to a pH of 8 and extra is triggered three times. After stirring.
The mass spectrum of chemical ionization of 45 vanilla of the combined extracts with anhydrous- (M + H) 362 and Nj KjCOj, the resulting pale yellow-green solution is filtered and concentrated, resulting in a yield of 2.04 g (72.1%) of pale yellow syrup
ruyut as (allylamino) -2-bromo-3, 50 identified as 4- (allylamide5-dichloroacetophenone), Ho) -oi- (tret-butylamino) methyl J -3.5IC spectrum (pure): 3330J 1670, dichlorobenzyl alcohol, IR spectrum
(clean): 3400,
Nuclear Magnetic Resonance Spectrum (PLS) 3: 7.32 (blue multiplet, 1, CH): 5.50-5.00 2, Ag-H) J 6.35-5.60 (complex- (complex multiplet, 2, CHj ) ;: ny multiplet, 1, CH) 5.45-4.95 1
4.84 (Li, triplet, 1, NH); 4.37 (syn-2, CH), 4.52 (doublet of the doublet, 1,
Br-CH), 3.97 (overlap multiplet.
B, .3.49 g (12.2%) less than a flowing brown syrup; identifies the NMR spectrum (CDCl,) 7.83 (singlet, 2, AR-H) i 6.35-6.65 (complexglet, 2 , CH, jBr) j 4.20 (LP, multiplet, 2, CIS).
3, Ar-NSNg); 3.03 (Lg, singlet, 2,
chlorobenzyl alcohol of formula
 Example 31, 4- (Allyl vol- (tert-butylamino) methyl-3, 8.92 mol) in 10 ml is added l for 1 hour to stir the solution of tert-butyl amine (1, ° by cooling with a mixture of dry ice - CC14.
p sludge in 1 rd ear
C1
 Example 31, 4- (allyl (t-butylamino) methyl-3.5, 92 mol) in 10 ml is added in m for 1 h to stirring the solution of tert-butylamine (1.34 ° by cooling with a mixture of dry ice - SS14. About
CHg-CHCHjNH-Q-CHCHj-Nvic (CHj), CI HE
 Example 31, 4- (Allylamino) -b- (tert-butylamino) methyl-3.5 di-8.92 mol) in 10 ml is added dropwise per 1 hour to the stirred solution of tert-butylamine (1.34 g ° - by cooling in a dry ice bath - CC14.
Solution-4- (allylamino) -2-bromo-3, 5-dichloroacetophenone (2.88 g
 Example 31, 4- (Allylamino) -b- (tert-butylamino) methyl-3.5 di-8.92 mol) in 10 ml is added dropwise over 1 hour to the stirred solution of tert-butylamine (1.34 g ° - by cooling in a bath with a mixture of dry ice - CC14.
18.3 mmol) in 20 ml of tetrahydrofuran. The temperature of the reaction is maintained from
 Example 31, 4- (Allylamino) -b- (tert-butylamino) methyl-3.5 di-8.92 mol) in 10 ml is added dropwise over 1 hour to the stirred solution of tert-butylamine (1.34 d ° - by cooling in a dry ice bath with CC14.
My yellow suspension is heated to
room temperature for
30 min and stirred at 21–22 ° C.
for 1.5 hours. Sodium cyanoborohydride (2.80 g, 44.6 mmol) is added.
in two portions e for 5 minutes, resulting in a thick, tan-brown suspension with ssuat-o.
glacial acetic acid (ml) is added dropwise to the formation of a yellow solution, which is stirred at room temperature for 3 days. The reaction mixture is poured into a solution of 100 ml of water and 100 ml of a saturated aqueous solution of NaCl, the pH value of which is then adjusted to 7 with 10%, and extracted three times with Et, jO. The combined extracts are shaken with two portions of dilute aqueous HC1 which are combined, neutralized with 10%, to a pH of 8 and extra is triggered three times. After stirring
3, Ar-NSNg); 3.03 (Lg, singlet, 2,
2514
W and HE) - 2.68 (multiplet, 2,), 1.13 (singlet ,, 9, SSCH,),).
Chemical ionization mass spectrum (M + M) 317.
CHjClj / CH ZON / concentrated (80: 19: 1) shows one major point (, 6) with nine trace impurities. When standing, this syrup gradually crystallizes to a rust-brown solid.
Example 32, N-tert-Butyl-m-hydroxy-B-methylthiophenethylamine hydrochloride.
The process is carried out as described in Example. 3, and using methyl mercaptan instead of methanol, as in Example 25, the final compound „
Example 33 The following compounds are prepared according to the method described in example 13,
Cls Вй 9 -О- 1 СН2-КН-С (СНз) з
C1 / in
R,
n n n
four
H
n n
R,
M.p. WITH
1-C, H,
CH-CHj-CHj-CHj Oil 62-64 209 (HC1-salt) Benzyl 85-89
Cyclopentyl Oil Pikloheksil 194-198 (HC1-salt)
Example 34, ot - (tert-Butylmino) methyl 3-3,5-dichloro-4-diallylamine- obenzshtovy alcohol of the formula
Clv (CHj-CHCHi) 2-N-O CHCH2-NH-CtCHs) j
P li
The final compound is obtained by carrying out the process as described for the preparation of 4- (allylamino) (tert-butylamino) methyl-3,5-dichloro benzyl alcohol (Example 31). A pale yellow syrup, which gradually crystallizes on standing, identified as the target product
IR (pure): 3300, 1630 cm. Spectrum MP (CI) Clj: 7.26 (singlet, 2, AR-H) j 6.23-5.54 (complex multiplet, 2, CH) 5 , 32-4.87 (complex multiplet, 4, CH2); .4.48 (multiplet ,, AR-CH) j 3.78
6, 26
(multiplet with similarity to the doublet, 4, J-6 Hz, Ar-NCH); 3.4-2.0 (Fng, 2, NH, and OH); 2.62 (multiplet, 2,); 1.13 (singlet, 9, C (CHj) j, the mass spectrum of chemical ionization, equal to 357, corresponds to the mass spectrum of the final compound. Effective and preferred
the norms of the active ingredient in the feed ration depend to a certain extent on the type of animal and are given
in table 3-0
Feed compositions that provide the desired acceleration of animal growth and feed utilization efficiency can be obtained by mixing a fenshtatanov derivative or its acid additive salt, or feed additives containing the specified compound, with animal feed in an amount that provides the desired rate of active compound in this feed.
Feed additives can be learned by mixing 10-75% by weight of the phenylethane derivative or its acid addition salt and the active salt with 25-90% by weight of the appropriate carrier or diluent. Carriers suitable for use in formulating feed additives include alfalfa flour, soy bean flour, cotton flour.
oils, cottonseed flour with the addition of sodium chloride, corn flour, molasses, urea, bone meal, corn cob flour, etc. The carrier accelerates the uniform distribution of the active ingredient in the feed into which the feed additive is added. In this way, the correct distribution of the active ingredient in the feed is guaranteed.
If the feed additive is used as the outer cover of the feed, it also contributes to the uniform distribution of the active compound in the feed enclosed in the cover.
If the composition is for parenteral administration, the phenylethane derivative may be formulated as a paste or tablet and may be administered as an implant, usually under
The scalp or ear of an animal being examined determines its growth rate and / or improved feed efficiency.
In practice, parenteral administration consists of injecting a sufficient amount of the indicated phenylstene derivative, for example, 0.001-50 mg / kg of animal weight. The preferred dose for cattle is 0.001-25 mg / kg animal weight for domestic poultry 0.001- 35 mg / kg body weight, for sheep and goats 0.001- 40 mg / kg animal weight, 0.001- 35 mg / kg rabbit weight.
Recipe paste as a paste can be prepared by dispersing the active phenylethane derivative in a pharmaceutically acceptable oil, such as sesame oil, corn oil, sesame oil, corn oil, etc.
Tablets containing an effective dose of the phenylethane derivative can be prepared by blending with the diluted active ingredient with a diluent such as carbovax (solid polyethylene glycol), biodegradable polymers, carcube wax, etc. A lubricant, such as magnesium stearate or kg / l stearate, can be added to the composition to improve the process.
preparation of tablets.
More than one tablet can be administered to an animal to achieve a dose that provides a higher growth rate and / or improved feed utilization in an animal. In addition, it has been found that, periodically, during this treatment of an animal, additional implants can be inserted to maintain the required rate of drug delivery in the animal's body.
In addition to the fact that the compounds according to the invention contribute to an increase in the growth rate and an improved feed utilization efficiency of animals, they increase the deposition in the body of the lean meat (i.e., muscle or protein)
and improve the quality of animal carcass by increasing the fasting ratio to the portion of meat / fat in the animal, resulting in these compounds. Thus, such a biological reaction, and provides for the introduction of animals into the body of the proposed compounds in the indicated doses, the behavior of animals and, therefore, their high value.

权利要求:
Claims (1)
[1]
Invention Formula
A method for producing a feed composition comprising mixing nutritional components with an active substance having a growth promoting effect, characterized in that, in order to absorb the composition activity and reduce the deposition of fat a, compounds of the structural formula
NRiBj
de X - hydrogen, halogen or group
CN;
Y is hydrogen, F,
NHCORj. or group
Z R, Rn -
U hydrogen
CPs C, is hydrogen, hydrogen.
halogen, OHCN, COOR,
Sc alkyl,
C, - € 4 - alkyl,
C (- Cg - alkyl, C ,, - C: alkenyl
or
 hydrogen, C, -C5-alksh1,
cycloalkyl, dimethylphenyl, benzyl, 3-phenylpropyl, hydrogen, OH; hydrogen. C, is alkyl chlorine, methyl or nitro, and its mixing with nutrients is carried out at the rate of 3-200 g per 1 ton.
4- - 629
I 416046
30 Table 1
35141604636
Continued table. 2
1-100 0.1-10 0.1-10 1-100
Sheep, goats Chicken ta, rabbits Turkey
Cattle and Pigs

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IL60530A|1979-08-16|1984-10-31|American Cyanamid Co|Animal feed compositions useful as growth promotors and for reduction of fat in animals,comprising phenylethanolamine derivatives and certain such novel compounds|EP0103830A3|1982-09-22|1985-07-31|Bayer Ag|Phenylethylemine derivatires as growth stimulators|

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DE3678252D1|1985-10-17|1991-04-25|American Cyanamid Co|ANTHRANILONITRILE DERIVATIVES AND RELATED COMPOUNDS AS USEFUL SUBSTANCES FOR ACCELERATING GROWTH, FOR IMPROVING THE QUALITY OF FOOD AND FOR INCREASING THE MEAT / FAT RATIO IN WARM BLOODED ANIMALS.|

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DK123788A|1987-03-10|1988-09-11|Beecham Group Plc|Morpholine-DERIVATIVES|

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DE3714485A1|1987-04-30|1988-11-17|Bayer Ag|PYRROLOPHENYL ALKANOLAMINE AND THEIR DERIVATIVES, THE PROCESS FOR THEIR MANUFACTURING AND THEIR USE AS PROMOTERS|

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CN109912434A|2017-12-13|2019-06-21|上海安谱实验科技股份有限公司|The synthetic method of phenyl ethyl amine beta receptor agonist|

法律状态:

优先权:

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申请号 | 申请日 | 专利标题

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US18125580A| true| 1980-08-25|1980-08-25|

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US18125480A| true| 1980-08-25|1980-08-25|

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