USRE29467E - Benzylcyano-amides - Google Patents
Benzylcyano-amides Download PDFInfo
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- USRE29467E USRE29467E US05/722,355 US72235576A USRE29467E US RE29467 E USRE29467 E US RE29467E US 72235576 A US72235576 A US 72235576A US RE29467 E USRE29467 E US RE29467E
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- United States
- Prior art keywords
- cyano
- product
- trimethoxy
- general formula
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- Expired - Lifetime
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- QIRSDXBXWUTMRE-UHFFFAOYSA-N benzylcyanamide Chemical class N#CNCC1=CC=CC=C1 QIRSDXBXWUTMRE-UHFFFAOYSA-N 0.000 title 1
- LVWCNSSTYGZBCQ-UHFFFAOYSA-N 2-cyano-3-(3,4,5-trimethoxyphenyl)propanamide Chemical compound COC1=CC(CC(C#N)C(N)=O)=CC(OC)=C1OC LVWCNSSTYGZBCQ-UHFFFAOYSA-N 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 abstract description 4
- XHPZVBGIPQQTQW-UHFFFAOYSA-N 5-benzylpyrimidine-2,4-diamine Chemical class NC1=NC(N)=NC=C1CC1=CC=CC=C1 XHPZVBGIPQQTQW-UHFFFAOYSA-N 0.000 abstract description 2
- 239000002253 acid Substances 0.000 abstract description 2
- 150000001408 amides Chemical class 0.000 abstract description 2
- 239000000543 intermediate Substances 0.000 abstract description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
- 150000001875 compounds Chemical class 0.000 description 10
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 239000000203 mixture Substances 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 5
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 5
- 238000005984 hydrogenation reaction Methods 0.000 description 5
- OPHQOIGEOHXOGX-UHFFFAOYSA-N 3,4,5-trimethoxybenzaldehyde Chemical compound COC1=CC(C=O)=CC(OC)=C1OC OPHQOIGEOHXOGX-UHFFFAOYSA-N 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 239000003610 charcoal Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 239000012442 inert solvent Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- GZVUCCJMRWRHSF-UHFFFAOYSA-N 2,6-diamino-5-benzyl-1h-pyrimidin-4-one Chemical class OC1=NC(N)=NC(N)=C1CC1=CC=CC=C1 GZVUCCJMRWRHSF-UHFFFAOYSA-N 0.000 description 2
- SULXVPFOQLMBGA-UHFFFAOYSA-N 2-cyano-3-(3,4,5-trimethoxyphenyl)prop-2-enamide Chemical compound COC1=CC(C=C(C#N)C(N)=O)=CC(OC)=C1OC SULXVPFOQLMBGA-UHFFFAOYSA-N 0.000 description 2
- JFRKQRNPLPJBQG-UHFFFAOYSA-N 2-cyano-3-(3,4,5-trimethoxyphenyl)prop-2-enoic acid Chemical compound COC1=CC(C=C(C#N)C(O)=O)=CC(OC)=C1OC JFRKQRNPLPJBQG-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- STIAPHVBRDNOAJ-UHFFFAOYSA-N carbamimidoylazanium;carbonate Chemical compound NC(N)=N.NC(N)=N.OC(O)=O STIAPHVBRDNOAJ-UHFFFAOYSA-N 0.000 description 2
- MLIREBYILWEBDM-UHFFFAOYSA-N cyanoacetic acid Chemical compound OC(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-N 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- -1 piperidine Chemical class 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- WJUFSDZVCOTFON-UHFFFAOYSA-N veratraldehyde Chemical compound COC1=CC=C(C=O)C=C1OC WJUFSDZVCOTFON-UHFFFAOYSA-N 0.000 description 2
- RNHDAKUGFHSZEV-UHFFFAOYSA-N 1,4-dioxane;hydrate Chemical compound O.C1COCCO1 RNHDAKUGFHSZEV-UHFFFAOYSA-N 0.000 description 1
- UCTUXUGXIFRVGX-UHFFFAOYSA-N 2,3,4-trimethoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C(OC)=C1OC UCTUXUGXIFRVGX-UHFFFAOYSA-N 0.000 description 1
- BTEMUZIMVZVNAL-UHFFFAOYSA-N 2,6-diamino-5-[(3,4-dimethoxyphenyl)methyl]-1h-pyrimidin-4-one Chemical compound C1=C(OC)C(OC)=CC=C1CC1=C(N)N=C(N)N=C1O BTEMUZIMVZVNAL-UHFFFAOYSA-N 0.000 description 1
- RKQHMXZJCSRJFN-UHFFFAOYSA-N 2-cyano-3-(3,4,5-trimethoxyphenyl)propanoic acid Chemical compound COC1=CC(CC(C#N)C(O)=O)=CC(OC)=C1OC RKQHMXZJCSRJFN-UHFFFAOYSA-N 0.000 description 1
- UHGNGGISEFEZHE-UHFFFAOYSA-N 2-cyano-3-(3,4-dimethoxyphenyl)prop-2-enamide Chemical compound COC1=CC=C(C=C(C#N)C(N)=O)C=C1OC UHGNGGISEFEZHE-UHFFFAOYSA-N 0.000 description 1
- XMPQKMVQQAVHDS-UHFFFAOYSA-N 2-cyano-3-(3,4-dimethoxyphenyl)propanamide Chemical compound COC1=CC=C(CC(C#N)C(N)=O)C=C1OC XMPQKMVQQAVHDS-UHFFFAOYSA-N 0.000 description 1
- FYJKTYLNKCUCLP-UHFFFAOYSA-N 6-hydroxytrimethoprim Chemical compound COC1=C(OC)C(OC)=CC(CC=2C(=NC(N)=NC=2N)O)=C1 FYJKTYLNKCUCLP-UHFFFAOYSA-N 0.000 description 1
- 101100386054 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) CYS3 gene Proteins 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 125000003277 amino group Chemical class 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- DGJMPUGMZIKDRO-UHFFFAOYSA-N cyanoacetamide Chemical compound NC(=O)CC#N DGJMPUGMZIKDRO-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 150000002357 guanidines Chemical class 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- OENLEHTYJXMVBG-UHFFFAOYSA-N pyridine;hydrate Chemical compound [OH-].C1=CC=[NH+]C=C1 OENLEHTYJXMVBG-UHFFFAOYSA-N 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 101150035983 str1 gene Proteins 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
Definitions
- the present invention relates to benzylcyano-acids and amides of general formula I ##STR1## wherein R 1 and R 2 are each selected from among the group consisting of hydrogen, halogen, lower alkyl and lower alkoxy, R 3 and R 4 are each a lower alkoxy group, Y is selected from the group consisting of hydroxy, and an unsubstituted or alkyl-substituted amino group and the dotted line designates either an additional C--C bond or hydrogen atoms, excluding ⁇ -cyano-3,4,5-trimethoxy-cinnamic acid.
- the compounds of formula I are valuable intermediates in a process for the preparation of certain 2,4-diamino-5-benzyl-6-hydroxy-pyrimidines which in turn are easly transformed to pharmaceutically valuable 2,4-diamino-5-benzyl pyrimidines as described in our co-pending Application No. 309,757 filed concurrently herewith.
- the compound of general formula IV is hydrogenated catalytically with a suitable catalyst in a suitable inert solvent to yield the desired compound of general formula V ##STR4## in which R 1 , R 2 , R 3 , R 4 and Y are as defined above.
- the basic catalyst used in the first reaction step is preferably a secondary amine e.g., piperidine, a metal alkoxide or sodium or potassium hydroxide.
- This step is performed in an inert solvent such as an alcohol e.g., methanol, ethanol, isopropanol, ethers, e.g., dioxane, tetrahydrofuran, pyridine water.
- Said step is preferably performed at elevated temperatures, e.g., between 40°-80°. (All temperatures indicated herein are in degrees centigrade).
- catalysts for the hydrogenation step there may be mentioned, e.g. palladized or platinized charcoal.
- suitable solvents there may be mentioned ethyl acetate; alcohols, e.g. methanol, ethanol, isopropanol, ethers, e.g. dioxane; etc.
- the present invention also relates to a process for the preparation of 2,4-diamino-5-benzyl-6-hydroxypyrimidines in which a compound of general formula V is, without a solvent or in the presence of a suitable solvent, reacted with guanidine to yield a compound of general formula VI ##STR5## in which R 1 , R 2 , R 3 and R 4 are as defined above.
- the condensation with guanidine when being performed in an inert solvent, is performed preferably in an alcohol such as methanol, ethanol, isopropanol, etc.
- Example 2 100 g of ⁇ -cyano-3,4,5-trimethoxy-cinnamic acid obtained as in Example 1 were dissolved in a solution of 16 g of sodium hydroxide in 1 liter of water and then 7.5 g of 5% of palladized charcoal were added. The mixture was hydrogenated at atmospheric pressure until the absorption of hydrogen had stopped. The catalyst was removed and 175 cc of 10% hydrochloric acid were added. The resulting precipitate was filtered off, washed with 200 cc of water and dried in vacuo at 50° for 10 hours to yield 93.1 g (93%) of ⁇ -cyano-3,4,5-trimethoxy-dihydrocinnamic acid: m.p. 102°-105°. A pure sample, recrystallized from chloroform melted at 104°-105°.
- Example 8 This example was run exactly as described in Example 5 except that 50 g of the product of Example 8, 10 g of sodium and 38.5 g. of guanidine carbonate in 0.5 liter of dry methanol were used.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Benzylcyano-acids and amides useful as intermediates in the preparation of pharmaceutically valuable 2,4-diamino-5-benzyl pyrimidines.
Description
The present invention relates to benzylcyano-acids and amides of general formula I ##STR1## wherein R1 and R2 are each selected from among the group consisting of hydrogen, halogen, lower alkyl and lower alkoxy, R3 and R4 are each a lower alkoxy group, Y is selected from the group consisting of hydroxy, and an unsubstituted or alkyl-substituted amino group and the dotted line designates either an additional C--C bond or hydrogen atoms, excluding α-cyano-3,4,5-trimethoxy-cinnamic acid.
The compounds of formula I are valuable intermediates in a process for the preparation of certain 2,4-diamino-5-benzyl-6-hydroxy-pyrimidines which in turn are easly transformed to pharmaceutically valuable 2,4-diamino-5-benzyl pyrimidines as described in our co-pending Application No. 309,757 filed concurrently herewith.
This application also discloses a process for the preparation of compounds of general formula I wherein:
A. an aldehyde of general formula II ##STR2## in which R1, R2, R3, and R4, are as defined above is reacted in the presence of a suitable basic catalyst with a compound of general formula III
NC--CH.sub.2 --COY
in which Y is as defined above to yield a compound of general formula IV ##STR3## in which R1, R2, R3, R4 and Y are as defined above; and, if desired.
B. the compound of general formula IV is hydrogenated catalytically with a suitable catalyst in a suitable inert solvent to yield the desired compound of general formula V ##STR4## in which R1, R2, R3, R4 and Y are as defined above. The basic catalyst used in the first reaction step is preferably a secondary amine e.g., piperidine, a metal alkoxide or sodium or potassium hydroxide. This step is performed in an inert solvent such as an alcohol e.g., methanol, ethanol, isopropanol, ethers, e.g., dioxane, tetrahydrofuran, pyridine water. Said step is preferably performed at elevated temperatures, e.g., between 40°-80°. (All temperatures indicated herein are in degrees centigrade).
As preferred catalysts for the hydrogenation step there may be mentioned, e.g. palladized or platinized charcoal. As suitable solvents there may be mentioned ethyl acetate; alcohols, e.g. methanol, ethanol, isopropanol, ethers, e.g. dioxane; etc.
The present invention also relates to a process for the preparation of 2,4-diamino-5-benzyl-6-hydroxypyrimidines in which a compound of general formula V is, without a solvent or in the presence of a suitable solvent, reacted with guanidine to yield a compound of general formula VI ##STR5## in which R1, R2, R3 and R4 are as defined above.
The condensation with guanidine, when being performed in an inert solvent, is performed preferably in an alcohol such as methanol, ethanol, isopropanol, etc.
The invention will now be illustrated with reference to the following examples without, however, being limited thereto.
A mixture of 100 g of 3,4,5-trimethoxy-benzaldehyde and 43.5 g of cyanoacetic acid in 1 liter of water containing 21 g of sodium hydroxide was stirred for 2 hours at 50°. The clear solution that was thereby obtained was cooled, 120 cc of 5 N hydrochloric acid were added and after additional cooling the resulting precipitate was filtered off and washed with 200 cc of water. The crude material was dried at 80° and used in the hydrogenation step without further purification. It melted at 221°-224°. The yield of α-cyano-3,4-5-trimethoxy-cinnamic acid was 126 g (94%).
100 g of α-cyano-3,4,5-trimethoxy-cinnamic acid obtained as in Example 1 were dissolved in a solution of 16 g of sodium hydroxide in 1 liter of water and then 7.5 g of 5% of palladized charcoal were added. The mixture was hydrogenated at atmospheric pressure until the absorption of hydrogen had stopped. The catalyst was removed and 175 cc of 10% hydrochloric acid were added. The resulting precipitate was filtered off, washed with 200 cc of water and dried in vacuo at 50° for 10 hours to yield 93.1 g (93%) of α-cyano-3,4,5-trimethoxy-dihydrocinnamic acid: m.p. 102°-105°. A pure sample, recrystallized from chloroform melted at 104°-105°.
100 g of 3,4,5-trimethoxy-benzaldehyde and 44 g of α-cyano-acetamide were dissolved in 300 cc of dry pyridine at 50°. To this solution 10 cc of piperidine were added and the mixture was heated at 50° with stirring for 2 hours. The reaction mixture was cooled at room temperature, filtered off and the precipitate was washed on the filter with 50 cc of cold isopropanol. The product was dried at 80° to yield 123.6 g (92.5%) of α-cyano-3,4,5-trimethoxy-cinnamamide; m.p. 192°-194°. This product was used for the hydrogenation step without further purification. A pure sample, recrystallized from isopropanol, melted at 193°-195°.
100 g of α-cyano-3,4,5-trimethoxy-cinnamamide obtained as in Example 3 were dissolved in 1 liter of a 9:1 mixture of dioxane-water and 7.5 g of 5% of palladized charcoal were added. The mixture was hydrogenated at atmospheric pressure until the absorption of hydrogen had stopped. The catalyst was removed and the solvent was evaporated under vacuum. The residue was recrystallized from ethyl acetate to obtain, after drying at 60° for 6 hours, 89.2 g (89%) of α-cyano-3,4,5-trimethoxy-dihydrocinnamamide; m.p. 128°-130°.
To a solution of 23 g of sodium in 1 liter of dry methanol, 90 g of guanidine carbonate were added and the mixture was stirred for 15 minutes at room temperature. The precipitated sodium carbonate was filtered off with suction over cellite and the solids were washed with 200 cc of methanol. To this guanidine solution in methanol were added 132 g of α-cyano-3,4,5-trimethoxy-dihydrocinnamimide prepared as described in Example 4. The solution was refluxed for 6 hours and the methanol was distilled off in vacuo. The residue was dissolved in 300 cc. of water and the product precipitated by the addition of 6N hydrochloric acid to pH 6. After allowing the product to cool at 0° for 2 hours the white solid was filtered off and washed with 40 cc of ice-cold water. The product was dried at 80°/5mm for 12 hours to yield 136.5 g (89%) of colorless 2,4-diamino-5-(3',4',5'-trimethoxy-benzyl)-6-hydroxy-pyrimidine, m.p. 275°-276°.
A mixture of 100 g of α-cyano-3,4,5-trimethoxydihydrocinnamamide and 60 g of freshly prepared guanidine was heated at 110° for 1 hour with occasional stirring. The reaction mixture was dissolved in 75 cc of hot water and the solution was filtered. The product was precipitated by adding to the clear filtrate, 6N hydrochloric acid to pH 6. After allowing to cool at 0° for 4 hours, the solid was filtered off and washed with 30 cc of ice-cold water. The product was dried at 80°/5mm for 12 hours to obtain 106.7 g (92%) of a compound (m.p. 274°-276°), which was identical with the compound obtained in Example 5.
This example was carried out exactly as described in Example 3 except that 84.7 g of 3,4-dimethoxybenzaldehyde were used in place of the trimethoxybenzaldehyde. The product was dried at 80° to obtain 111.2 g (94%) of α-cyano-3',4'-dimethoxycinnamamide: m.p. 182°-185°. This product was used for the hydrogenation step without further purification. A pure sample, recrystallized from dimethyl formamide had a m.p. of 184°-185°.
The hydrogenation of 100 g. of α-cyano-3,4-dimethoxy-cinnamamide was carried out as described in Example 4. Crystallization of the product from dry ethanol yielded 90 g (90%) of α-cyano-3,4-dimethoxydihydrocinnamamide, m.p. 170°-171°.
This example was run exactly as described in Example 5 except that 50 g of the product of Example 8, 10 g of sodium and 38.5 g. of guanidine carbonate in 0.5 liter of dry methanol were used. The crystalline product 2,4 -diamino-5-(3'4'-dimethoxybenzyl)-6-hydroxy-pyrimidine, m.p. 268°-270° weighed 52 g (87.5%)
This example was carried out exactly as described in Example 6, except that 100 g of the Example of example 8 and 70 g of freshly prepared guanidine were used. The product obtained 2,4-diamino-5-(3',4'-dimethoxybenzyl)-6-hydroxy pyrimidine m.p. 268°-270° weighed 108 g. (91%).
Claims (1)
1. α-cyano-3,4,5-trimethoxy-dihydrocinnamamide.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IL38412A IL38412A (en) | 1971-12-20 | 1971-12-20 | Alpha-cyano-3,4,5-trialkoxycinnamic acid derivatives |
| IL38412 | 1971-12-20 | ||
| US309758A US3910984A (en) | 1972-11-27 | 1972-11-27 | Benzylcyano-amides |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US309758A Reissue US3910984A (en) | 1971-12-20 | 1972-11-27 | Benzylcyano-amides |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| USRE29467E true USRE29467E (en) | 1977-11-08 |
Family
ID=26320467
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US05/722,355 Expired - Lifetime USRE29467E (en) | 1971-12-20 | 1976-09-13 | Benzylcyano-amides |
Country Status (1)
| Country | Link |
|---|---|
| US (1) | USRE29467E (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4853403A (en) | 1985-07-29 | 1989-08-01 | Kanegafuchi Kagaku Kogyo Kabushiki Kaisha | 3-phenylthiomethylstyrene derivative, process for preparing the same, and antiallergic agent and tyrosinekinase inhibiting agent containing the same |
| US4971996A (en) * | 1987-03-11 | 1990-11-20 | Kanegafuchi Kagaku Kogyo Kabushiki Kaisha | Hydroxystyrene compounds which are useful as tyrosine kinase inhibitors |
| US5089516A (en) * | 1987-03-11 | 1992-02-18 | Kanegafuchi Kagaku Kogyo Kabushiki Kaisha | 1-phenyl-3,5-pyrazolidinedione hydroxystyrene compounds which have tyrosine kinase inhibiting activity |
| US5202341A (en) * | 1987-03-11 | 1993-04-13 | Kanegafuchi Kagaku Kogyo Kabushiki Kaisha | Hydroxystyrene compounds having tyrosine kinase inhibiting activity |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3462475A (en) * | 1961-03-29 | 1969-08-19 | Gaf Corp | Alpha-cyano-beta-alkyl substituted cinnamic acid amides |
| US3671564A (en) * | 1965-10-28 | 1972-06-20 | Burroughs Wellcome Co | Benzylidene cyano-acetals |
| US3676482A (en) * | 1969-03-14 | 1972-07-11 | Merck & Co Inc | Racemization of an alpha-methyl dopa derivative |
-
1976
- 1976-09-13 US US05/722,355 patent/USRE29467E/en not_active Expired - Lifetime
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3462475A (en) * | 1961-03-29 | 1969-08-19 | Gaf Corp | Alpha-cyano-beta-alkyl substituted cinnamic acid amides |
| US3671564A (en) * | 1965-10-28 | 1972-06-20 | Burroughs Wellcome Co | Benzylidene cyano-acetals |
| US3676482A (en) * | 1969-03-14 | 1972-07-11 | Merck & Co Inc | Racemization of an alpha-methyl dopa derivative |
Non-Patent Citations (3)
| Title |
|---|
| Holmes et al., Can. J. Chem., vol. 47, pp. 4076-4077 (1969). * |
| Sanchez-Viesca, Chemical Abstracts, vol. 66, 28475v (1967). * |
| Schiemenz et al., Chem. Ber., vol. 95, pp. 967-970 (1962). * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4853403A (en) | 1985-07-29 | 1989-08-01 | Kanegafuchi Kagaku Kogyo Kabushiki Kaisha | 3-phenylthiomethylstyrene derivative, process for preparing the same, and antiallergic agent and tyrosinekinase inhibiting agent containing the same |
| US4971996A (en) * | 1987-03-11 | 1990-11-20 | Kanegafuchi Kagaku Kogyo Kabushiki Kaisha | Hydroxystyrene compounds which are useful as tyrosine kinase inhibitors |
| US5057538A (en) * | 1987-03-11 | 1991-10-15 | Kanegafuchi Kagaku Kogyo Kabushiki Kaisha | Hydroxystyrene compounds which have useful pharmaceutical utility |
| US5089516A (en) * | 1987-03-11 | 1992-02-18 | Kanegafuchi Kagaku Kogyo Kabushiki Kaisha | 1-phenyl-3,5-pyrazolidinedione hydroxystyrene compounds which have tyrosine kinase inhibiting activity |
| US5202341A (en) * | 1987-03-11 | 1993-04-13 | Kanegafuchi Kagaku Kogyo Kabushiki Kaisha | Hydroxystyrene compounds having tyrosine kinase inhibiting activity |
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