NO137088B - PROCEDURES FOR THE PREPARATION OF BENZAMIDE DERIVATIVES - Google Patents
PROCEDURES FOR THE PREPARATION OF BENZAMIDE DERIVATIVES Download PDFInfo
- Publication number
- NO137088B NO137088B NO4695/71A NO469571A NO137088B NO 137088 B NO137088 B NO 137088B NO 4695/71 A NO4695/71 A NO 4695/71A NO 469571 A NO469571 A NO 469571A NO 137088 B NO137088 B NO 137088B
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- Norway
- Prior art keywords
- amino
- acid
- general formula
- preparation
- dialkylalkylenediamine
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 11
- 238000002360 preparation method Methods 0.000 title claims description 3
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical class NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 title description 3
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 12
- DMSZORWOGDLWGN-UHFFFAOYSA-N ctk1a3526 Chemical compound NP(N)(N)=O DMSZORWOGDLWGN-UHFFFAOYSA-N 0.000 claims description 7
- 239000005711 Benzoic acid Substances 0.000 claims description 6
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 5
- 235000010233 benzoic acid Nutrition 0.000 claims description 5
- 150000001558 benzoic acid derivatives Chemical class 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 229940054066 benzamide antipsychotics Drugs 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000002947 alkylene group Chemical group 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 238000011065 in-situ storage Methods 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims 1
- 150000002367 halogens Chemical group 0.000 claims 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- 150000001875 compounds Chemical class 0.000 description 11
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- -1 ethylene, propylene, butylene, isobutylene Chemical group 0.000 description 6
- 239000007858 starting material Substances 0.000 description 5
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 4
- 239000012442 inert solvent Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 125000004103 aminoalkyl group Chemical group 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 229960004050 aminobenzoic acid Drugs 0.000 description 2
- 229960004909 aminosalicylic acid Drugs 0.000 description 2
- 239000000730 antalgic agent Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 150000003936 benzamides Chemical class 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 229940125723 sedative agent Drugs 0.000 description 2
- 239000000932 sedative agent Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- DSPXASHHKFVPCL-UHFFFAOYSA-N 1-isocyanocyclohexene Chemical compound [C-]#[N+]C1=CCCCC1 DSPXASHHKFVPCL-UHFFFAOYSA-N 0.000 description 1
- IOHPVZBSOKLVMN-UHFFFAOYSA-N 2-(2-phenylethyl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1CCC1=CC=CC=C1 IOHPVZBSOKLVMN-UHFFFAOYSA-N 0.000 description 1
- WHXLHIGUTBQVOF-UHFFFAOYSA-N 4-amino-5-bromo-2-methoxybenzoic acid Chemical compound COC1=CC(N)=C(Br)C=C1C(O)=O WHXLHIGUTBQVOF-UHFFFAOYSA-N 0.000 description 1
- RVEATKYEARPWRE-UHFFFAOYSA-N 4-amino-5-chloro-2-methoxybenzoic acid Chemical compound COC1=CC(N)=C(Cl)C=C1C(O)=O RVEATKYEARPWRE-UHFFFAOYSA-N 0.000 description 1
- WKPRECBIRGXIAB-UHFFFAOYSA-N CCNN(NCC)P(N)(=O)NCC Chemical compound CCNN(NCC)P(N)(=O)NCC WKPRECBIRGXIAB-UHFFFAOYSA-N 0.000 description 1
- GZOYAPPUYJGHOC-UHFFFAOYSA-N Cl[IH]C1=CC=CC=C1 Chemical compound Cl[IH]C1=CC=CC=C1 GZOYAPPUYJGHOC-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 239000003416 antiarrhythmic agent Substances 0.000 description 1
- 239000002111 antiemetic agent Substances 0.000 description 1
- 229940125683 antiemetic agent Drugs 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- SXDBWCPKPHAZSM-UHFFFAOYSA-N bromic acid Chemical compound OBr(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000012320 chlorinating reagent Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- UDGSVBYJWHOHNN-UHFFFAOYSA-N n',n'-diethylethane-1,2-diamine Chemical compound CCN(CC)CCN UDGSVBYJWHOHNN-UHFFFAOYSA-N 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- ZUTNAPRHBFFUBV-UHFFFAOYSA-N pyrrolidine-2,5-dione;hydrochloride Chemical compound Cl.O=C1CCC(=O)N1 ZUTNAPRHBFFUBV-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/22—Amides of acids of phosphorus
- C07F9/224—Phosphorus triamides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
Foreliggende oppfinnelse angår en fremgangsmåte ved frem- The present invention relates to a method by producing
stilling av 4-amino-2,5-substituerte N,N-(dialkylalkylendiamin)- position of 4-amino-2,5-substituted N,N-(dialkylalkylenediamine)-
benzamider og salter derav. Nærmere bestemt er den nye fremgangs- benzamides and salts thereof. More specifically, the new progress
måte karakterisert ved at eh 4-amino-2,5-substituert benzoesyre av den generelle formel: way characterized in that eh 4-amino-2,5-substituted benzoic acid of the general formula:
hvor X og har de følgende angitte betydninger, omsettes med et, where X and have the following specified meanings, are replaced by a,
in situ fra N,N-dialkylalkylendiamin og fosforoxyklorid dannet N,N-dialkylaminoalkylenfosforamid av den generelle formel: in situ from N,N-dialkylalkylenediamine and phosphorus oxychloride formed N,N-dialkylaminoalkylene phosphoramide of the general formula:
eller et salt derav, hvor A, R^ og R2 har de følgende angitte be- or a salt thereof, where A, R 1 and R 2 have the following indicated
tydninger. interpretations.
Forbindelsene som fremstilles ifølge foreliggende opp- The compounds produced according to the present invention
finnelse har følgende generelle formel: invention has the following general formula:
hvor A er en lavere alkylengruppe, f.eks. ethylen, propylen, butylen, isobutylen, X er et halogenatom, f.eks. F, Cl, Br, eller hydrogenatom, R-L og R2" er like eller forskjellige, eri lavere' alky.lgruppe, f.eks. methyl, ethyl, propyl, og R^ er en lavere alkoxygruppe, f.eks. methoxy, ethoxy, eller hydroxylgruppe eller hydrogenatom. where A is a lower alkylene group, e.g. ethylene, propylene, butylene, isobutylene, X is a halogen atom, e.g. F, Cl, Br, or hydrogen atom, R-L and R 2" are the same or different, eri lower alkyl group, e.g. methyl, ethyl, propyl, and R 1 is a lower alkoxy group, e.g. methoxy, ethoxy , or hydroxyl group or hydrogen atom.
Blant forbindelsene omfattes også salter av forbindelsene av den ovenfor angitte formel, f.eks. et salt av saltsyre, hydro-. bromsyre, hydrojodsyre, vinsyre, eddiksyre og lignende. The compounds also include salts of the compounds of the above formula, e.g. a salt of hydrochloric acid, hydro-. bromic acid, hydroiodic acid, tartaric acid, acetic acid and the like.
Forbindelsene har farmakologiske egenskaper, og er nyttige som analge.tiske-, sedative-, neuroléptiske- og beroligende midler. I særdeleshet er ^-amino-N-(tert.aminoalkyl)-benzamider nyttige som anti-arrhytmetisk middel, 2-hydroxy-^-amino-N-Ctert.aminoalkyl)-benzamid er nyttig som analgétisk middel og 2-methoxy-lf-amino-5-klor-N-(tert.aminoalkyl)-benzamid er nyttig som antiemetisk middel. The compounds have pharmacological properties, and are useful as analgesics, sedatives, neuroleptics and sedatives. In particular, ^-amino-N-(tert.aminoalkyl)benzamides are useful as anti-arrhythmic agents, 2-hydroxy-^-amino-N-Ctert.aminoalkyl)benzamide is useful as an analgesic agent and 2-methoxy-lf -amino-5-chloro-N-(tert.aminoalkyl)-benzamide is useful as an antiemetic agent.
Omsetningen er vist ved folgende reaksjonsskjema: The turnover is shown by the following reaction scheme:
hvor A, X, R-p R2 og R^ har de ovenfor angitte betydninger. I det tilfelle hvor både R^ og X er H er det uheldig å angi forbindelsen som 2,5-substituert, men den er likevel for enkelthets.skyld angitt slik. where A, X, R-p, R2 and R^ have the meanings indicated above. In the case where both R 1 and X are H, it is unfortunate to indicate the compound as 2,5-substituted, but it is nevertheless indicated as such for the sake of simplicity.
Omsetningen mellom N,N-dialkylaminoalkylenfosforamid og den ^--amino-2,5-substituerte benzoesyre kan. utfores ved å oppvarme den til 50 - 150°C i et inert løsningsmiddel. Som inert løsningsmiddel kan anvendes et aromatisk eller alifatisk.hydrocarbon, f.eks. benzen, toluen, xylen, hexan, octan, etc. eller dimethylformamid, kloroform, fortrinnsvis•benzen eller toluen. The reaction between N,N-dialkylaminoalkylene phosphoramide and the ^--amino-2,5-substituted benzoic acid can. is carried out by heating it to 50 - 150°C in an inert solvent. An aromatic or aliphatic hydrocarbon can be used as an inert solvent, e.g. benzene, toluene, xylene, hexane, octane, etc. or dimethylformamide, chloroform, preferably•benzene or toluene.
N,N-dialkylaminoalkylenfosforamid kan benyttes i form av et salt såvel som basen av den ovenfor angitte formel, og- i det tilfelle det anvendes i form av et salt, erholdes den onskede forbindelse også N,N-dialkylaminoalkylene phosphoramide can be used in the form of a salt as well as the base of the above formula, and - in the case that it is used in the form of a salt, the desired compound is also obtained
i form av et salt. in the form of a salt.
N,N-dialkylaminoalkylenfosforamidet som er et av utgangsmateri-• alene i foreliggende fremgangsmåte er en ny forbindelse og denne kan fremstilles ved å omsette N,N-dialkylalkylendiamin med fosforoxyklorid og det erholdte salt er et stabilt krystallinsk salt. Eksempelvis er forbindelsen av følgende formel: The N,N-dialkylaminoalkylene phosphoramide which is one of the starting materials in the present method is a new compound and this can be prepared by reacting N,N-dialkylalkylenediamine with phosphorus oxychloride and the resulting salt is a stable crystalline salt. For example, the compound is of the following formula:
som fremstilles fra diethylendiamin og fosforoxyklorid et stabilt hvitt krystallinsk stoff med smeltepunkt 155°C, og en oljeaktig base kan lett erholdes ved å tilsette alkali til det krystallinske stoff. which is prepared from diethylenediamine and phosphorus oxychloride a stable white crystalline substance with a melting point of 155°C, and an oily base can be easily obtained by adding alkali to the crystalline substance.
Fremstilling av det nye utgangsmateriale kan utfores ved å lose 3 mol N,N-dialkylalkylendiamin i et inert løsningsmiddel og der-etter tilsette 1 mol fosforoxyklorid ved fra omgivende temperatur til losningsmidlets tilbakeløpstemperatur, hvorved N,N-dialkyl-aminoalkylenfosforamid kan erholdes praktisk talt kvantitativt. Som.inert løsningsmiddel kan anvendes det samme som de som er angitt for foreliggende fremgangsmåte. Preparation of the new starting material can be carried out by dissolving 3 mol of N,N-dialkylalkylenediamine in an inert solvent and then adding 1 mol of phosphorus oxychloride at from ambient temperature to the reflux temperature of the solvent, whereby N,N-dialkylaminoalkylene phosphoramide can be obtained practically quantitatively . As an inert solvent, the same as those specified for the present method can be used.
Benzoesyrederivatet som er det annet av utgangsmaterialene som anvendes i foreliggende fremgangsmåte, kan fremstilles fra konven-sjonell p-aminobenzoesyre, p-aminosalicylsyre og derivater derav. For eksempel kan 2-hydroxy-<1>+-amino-5-klorbenzoesyre fremstilles ved å omsette p-aminosalicylsyre med et spesielt klorineringsmiddel, slik som fenyljodklorid, jodtriklorid.og succinimidklorid. 2-alkoxy-^-amino-5-halo-benzoesyre kan fremstilles ved å alkoxylere 2-hydroxy-<1>+-amino-5-halobenzoesyre med et vanlig alkyleringsmiddel. Substituentene i 2-og 5-stilling i p-aminobenzoesyren kan innfores etter dannelsen av syreamidkombinasjonen ved foreliggende fremgangsmåte som angitt ovenfor. The benzoic acid derivative, which is the second of the starting materials used in the present method, can be prepared from conventional p-aminobenzoic acid, p-aminosalicylic acid and derivatives thereof. For example, 2-hydroxy-<1>+-amino-5-chlorobenzoic acid can be prepared by reacting p-aminosalicylic acid with a special chlorinating agent, such as phenyliodochloride, iodinetrichloride and succinimide chloride. 2-Alkoxy-^-amino-5-halo-benzoic acid can be prepared by alkylating 2-hydroxy-<1>+-amino-5-halobenzoic acid with a common alkylating agent. The substituents in the 2- and 5-position in the p-aminobenzoic acid can be introduced after the formation of the acid amide combination by the present method as stated above.
Foreliggende fremgangsmåte har den fordel at den ønskede forbindelse kan fremstilles direkte fra den ^-amino-2,5-substituerte benzoesyre uten å beskytte aminogruppen i ^--stilling, på grunn av anvendelse av N,N-dialkylaminoalkylenfosforamid som utgangsmateriale. Det er ikke tidligere kjent at et syreamid kan fremstilles ved- å omsette et alifatisk diaminderivat slik som N,N-dialkyl-aminoalkylenfosforamid med ^-amino-substituert benzoesyre som i foreliggende oppfinnelse. Selv om utgangsmaterialet N,N-dialkyl- . aminoalkylenfosforamid er en ny forbindelse, kan den lett fremstilles ved å omsette N,N-dialkylalkylendiamin med fosforoxyklorid, og dets salt er meget stabilt, hvorfor det ikke er nødvendig å ta for-holdsregler overfor fuktighet, og det er meget lett å håndtere. The present method has the advantage that the desired compound can be prepared directly from the ^-amino-2,5-substituted benzoic acid without protecting the amino group in the ^- position, due to the use of N,N-dialkylaminoalkylene phosphoramide as starting material. It is not previously known that an acid amide can be prepared by reacting an aliphatic diamine derivative such as N,N-dialkyl-aminoalkylene phosphoramide with ^-amino-substituted benzoic acid as in the present invention. Although the starting material N,N-dialkyl- . aminoalkylene phosphoramide is a new compound, it can be easily prepared by reacting N,N-dialkylalkylenediamine with phosphorus oxychloride, and its salt is very stable, so it is not necessary to take precautions against moisture, and it is very easy to handle.
Som ovenfor beskrevet er det ifølge foreliggende fremgangsmåte ikke nødvendig å beskytte aminogruppen ved 4-stilling, og heller ikke aktivere carboxylgruppen, og den ønskede forbindelse kan fremstilles under milde betingelser og i løpet av kort tid, hvorfor foreliggende fremgangsmåte representerer et betydelig tek-nisk fremskritt overfor de vanlige fremgangsmåter siden den letter reaksjonsgangen og minsker produksjonsomkostningene. Foreliggende oppfinnelse illustreres ved de følgende eksempler: As described above, according to the present method it is not necessary to protect the amino group at the 4-position, nor to activate the carboxyl group, and the desired compound can be prepared under mild conditions and within a short time, which is why the present method represents a significant technical advance compared to the usual methods since it facilitates the reaction and reduces the production costs. The present invention is illustrated by the following examples:
Eksempel 1 Example 1
I 100 ml benzen ble oppløst 11,6 g N,N-diethylethylendi-amin og tilsatt 5,1 g fosforoxyklorid ved romtemperatur. Omsetningen startet øyeblikkelig under dannelse av et krystallinsk bunnfall. Til blandingen ble tilsatt 20,2 g 2-methoxy-4-amino-5-klorbenzoe-syre> og blandingen ble derefter kokt under tilbakeløp. Efter av-kjøling ble det krystallinske bunnfall fraskilt ved filtrering, vasket med vann og tørket, hvorved der ble erholdt 85 g 2-methoxy-4-amino-5-klor-(N,N-diethylaminoethyl)-benzamid. 11.6 g of N,N-diethylethylenediamine were dissolved in 100 ml of benzene and 5.1 g of phosphorus oxychloride were added at room temperature. The reaction started immediately with the formation of a crystalline precipitate. To the mixture was added 20.2 g of 2-methoxy-4-amino-5-chlorobenzoic acid> and the mixture was then refluxed. After cooling, the crystalline precipitate was separated by filtration, washed with water and dried, whereby 85 g of 2-methoxy-4-amino-5-chloro-(N,N-diethylaminoethyl)-benzamide were obtained.
Utbytte: 95,5 %; sm.p. 145 - 147°C. Yield: 95.5%; sm.p. 145 - 147°C.
Elementæranalyse: C^4H22Cl ^ 2°2 Elemental analysis: C^4H22Cl ^ 2°2
Beregnet (<%>)<:> c = 56fQ9. H = 7;4o. N = 14,02; Cl = 11,82 Funnet (%): C = 56,21; H = 7,65; N = 13,97; Cl = 11,69 Calculated (<%>)<:> c = 56fQ9. H = 7.4o. N = 14.02; Cl = 11.82 Found (%): C = 56.21; H = 7.65; N = 13.97; Cl = 11.69
Eksempel 2 Example 2
12 g N,N-diethylaminoethylfosforamid ble omsatt med 22 g 2-methoxy-4-amino-5-brombenzoesyre i benzen, og reaksjonsblandingen ble behandlet som angitt i eksempel 1, hvorved der ble erholdt 30 g 2-methoxy-4-amino-5-brom-(N,N-diethylaminoethyl)-benzamid. 12 g of N,N-diethylaminoethylphosphoramide was reacted with 22 g of 2-methoxy-4-amino-5-bromobenzoic acid in benzene, and the reaction mixture was treated as indicated in example 1, whereby 30 g of 2-methoxy-4-amino- 5-Bromo-(N,N-diethylaminoethyl)-benzamide.
Utbytte: 96,8 %; sm.p. 135 - 136°C. Yield: 96.8%; sm.p. 135 - 136°C.
Elementæranalyse: C^H22Br N3°2Elemental analysis: C^H22Br N3°2
Beregnet (%): C = 48,85; H = 6,44; Br = 23,21; N = 12,21 Funnet (%): C = 48,79; H = 6,53; Br = 23,00; N = 12,39. Calculated (%): C = 48.85; H = 6.44; Br = 23.21; N = 12.21 Found (%): C = 48.79; H = 6.53; Br = 23.00; N = 12.39.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP45115341A JPS4940459B1 (en) | 1970-12-21 | 1970-12-21 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NO137088B true NO137088B (en) | 1977-09-19 |
| NO137088C NO137088C (en) | 1977-12-28 |
Family
ID=14660130
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO4695/71A NO137088C (en) | 1970-12-21 | 1971-12-20 | PROCEDURES FOR THE PREPARATION OF BENZAMIDE DERIVATIVES |
Country Status (28)
| Country | Link |
|---|---|
| JP (1) | JPS4940459B1 (en) |
| AR (1) | AR195064A1 (en) |
| AT (1) | AT314509B (en) |
| AU (1) | AU459435B2 (en) |
| BE (1) | BE776936A (en) |
| BG (2) | BG18860A3 (en) |
| CA (1) | CA981692A (en) |
| CH (2) | CH548985A (en) |
| CS (1) | CS174172B2 (en) |
| DE (1) | DE2162917B2 (en) |
| ES (1) | ES398146A1 (en) |
| FI (1) | FI55991C (en) |
| FR (1) | FR2118960B1 (en) |
| GB (1) | GB1353499A (en) |
| HU (1) | HU163170B (en) |
| IE (1) | IE35908B1 (en) |
| IL (1) | IL38417A (en) |
| LU (1) | LU64484A1 (en) |
| MC (1) | MC939A1 (en) |
| NL (1) | NL7117522A (en) |
| NO (1) | NO137088C (en) |
| OA (1) | OA03933A (en) |
| PH (1) | PH9783A (en) |
| PL (1) | PL88937B1 (en) |
| RO (1) | RO57372A (en) |
| SE (1) | SE402277B (en) |
| YU (1) | YU35341B (en) |
| ZA (1) | ZA718479B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE791677A (en) * | 1972-07-19 | 1973-03-16 | Renfag Sa | PROCESS FOR THE PREPARATION OF N- (DIETHYLAMINOETHYL) -2- METHOXY-5-METHYLSULFONYL-BENZAMIDE |
| BE793871A (en) * | 1972-07-19 | 1973-05-02 | Renfag Sa | PROCESS FOR THE PREPARATION OF N- (1-ETHYL-2- PYRROLIDYLMETYL) -2-METHOXT-5-ETHYLSULFONYL-BENZAMIDE AND ITS ADDITIONAL SALTS |
| CH614709A5 (en) * | 1975-09-25 | 1979-12-14 | Ciba Geigy Ag |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3170955A (en) * | 1958-04-25 | 1965-02-23 | Abbott Lab | Amino and halogen substituted-n-diloweralkylamino-alkyl-benzamides |
| NL281394A (en) * | 1961-07-25 |
-
1970
- 1970-12-21 JP JP45115341A patent/JPS4940459B1/ja active Pending
-
1971
- 1971-12-17 YU YU3163/71A patent/YU35341B/en unknown
- 1971-12-17 DE DE2162917A patent/DE2162917B2/en active Granted
- 1971-12-20 LU LU64484A patent/LU64484A1/xx unknown
- 1971-12-20 BG BG19283A patent/BG18860A3/xx unknown
- 1971-12-20 CA CA130,611A patent/CA981692A/en not_active Expired
- 1971-12-20 NO NO4695/71A patent/NO137088C/en unknown
- 1971-12-20 PL PL1971152310A patent/PL88937B1/pl unknown
- 1971-12-20 ES ES398146A patent/ES398146A1/en not_active Expired
- 1971-12-20 BE BE776936A patent/BE776936A/en not_active IP Right Cessation
- 1971-12-20 ZA ZA718479A patent/ZA718479B/en unknown
- 1971-12-20 IE IE1608/71A patent/IE35908B1/en unknown
- 1971-12-20 FR FR7145812A patent/FR2118960B1/fr not_active Expired
- 1971-12-20 NL NL7117522A patent/NL7117522A/xx unknown
- 1971-12-20 BG BG21828A patent/BG19601A3/xx unknown
- 1971-12-20 SE SE7116316A patent/SE402277B/en unknown
- 1971-12-20 MC MC964A patent/MC939A1/en unknown
- 1971-12-20 FI FI3619/71A patent/FI55991C/en active
- 1971-12-20 GB GB5910171A patent/GB1353499A/en not_active Expired
- 1971-12-20 AR AR239698A patent/AR195064A1/en active
- 1971-12-20 OA OA54443A patent/OA03933A/en unknown
- 1971-12-21 CH CH103773A patent/CH548985A/en not_active IP Right Cessation
- 1971-12-21 AT AT1094671A patent/AT314509B/en not_active IP Right Cessation
- 1971-12-21 AU AU37152/71A patent/AU459435B2/en not_active Expired
- 1971-12-21 PH PH13132A patent/PH9783A/en unknown
- 1971-12-21 RO RO69131A patent/RO57372A/ro unknown
- 1971-12-21 CS CS8867A patent/CS174172B2/cs unknown
- 1971-12-21 CH CH1866571A patent/CH545273A/en not_active IP Right Cessation
- 1971-12-21 HU HUSO1027A patent/HU163170B/hu unknown
- 1971-12-21 IL IL38417A patent/IL38417A/en unknown
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