CH424751A - Verfahren zur Herstellung von 5-Acylamino-2,4,6-trijodisophthalsäureamiden - Google Patents

Verfahren zur Herstellung von 5-Acylamino-2,4,6-trijodisophthalsäureamiden

Info

Publication number: CH424751A
Authority: CH; Switzerland
Prior art keywords: acid; solution; water; added; triiodoisophthalic
Prior art date: 1960-08-25

Application number

CH990261A

Other languages

German (de)

English (en)

Inventor

Brooke Hoey George

Original Assignee

Mallinckrodt Chemical Works

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1960-08-25

Filing date

1961-08-24

Publication date

1966-11-30

1961-06-26 Priority claimed from US119287A external-priority patent/US3145197A/en

1961-08-24 Application filed by Mallinckrodt Chemical Works filed Critical Mallinckrodt Chemical Works

1966-11-30 Publication of CH424751A publication Critical patent/CH424751A/de

Links

238000000034 method Methods 0.000 title claims description 34
230000008569 process Effects 0.000 title claims description 15
238000002360 preparation method Methods 0.000 title claims description 9
150000003839 salts Chemical class 0.000 claims description 22
239000003795 chemical substances by application Substances 0.000 claims description 18
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 14
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 12
125000000217 alkyl group Chemical group 0.000 claims description 8
238000006243 chemical reaction Methods 0.000 claims description 8
BWKWJRRDHNBJTI-UHFFFAOYSA-N 3-amino-5-carbamoyl-2,4,6-triiodobenzoic acid Chemical compound NC(=O)C1=C(I)C(N)=C(I)C(C(O)=O)=C1I BWKWJRRDHNBJTI-UHFFFAOYSA-N 0.000 claims description 6
239000012346 acetyl chloride Substances 0.000 claims description 5
150000001408 amides Chemical class 0.000 claims description 5
239000012442 inert solvent Substances 0.000 claims description 4
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 claims description 3
YWGHUJQYGPDNKT-UHFFFAOYSA-N hexanoyl chloride Chemical compound CCCCCC(Cl)=O YWGHUJQYGPDNKT-UHFFFAOYSA-N 0.000 claims description 3
125000002252 acyl group Chemical group 0.000 claims description 2
125000005907 alkyl ester group Chemical group 0.000 claims description 2
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 claims description 2
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims 2
150000002762 monocarboxylic acid derivatives Chemical class 0.000 claims 2
230000001419 dependent effect Effects 0.000 claims 1
239000000243 solution Substances 0.000 description 137
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 92
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 86
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 59
238000006386 neutralization reaction Methods 0.000 description 54
239000000203 mixture Substances 0.000 description 51
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 42
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 42
239000011630 iodine Substances 0.000 description 42
229910052740 iodine Inorganic materials 0.000 description 42
239000002253 acid Substances 0.000 description 40
159000000000 sodium salts Chemical class 0.000 description 38
239000000047 product Substances 0.000 description 36
238000003756 stirring Methods 0.000 description 33
-1 5-amino-isophthalic acid alkyl amide Chemical class 0.000 description 29
238000002844 melting Methods 0.000 description 21
230000008018 melting Effects 0.000 description 21
MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical class CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 20
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
UXIGWFXRQKWHHA-UHFFFAOYSA-N Iotalamic acid Chemical compound CNC(=O)C1=C(I)C(NC(C)=O)=C(I)C(C(O)=O)=C1I UXIGWFXRQKWHHA-UHFFFAOYSA-N 0.000 description 16
150000001875 compounds Chemical class 0.000 description 16
239000012043 crude product Substances 0.000 description 16
239000000706 filtrate Substances 0.000 description 16
NBDAHKQJXVLAID-UHFFFAOYSA-N 5-nitroisophthalic acid Chemical compound OC(=O)C1=CC(C(O)=O)=CC([N+]([O-])=O)=C1 NBDAHKQJXVLAID-UHFFFAOYSA-N 0.000 description 15
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 12
QZRGKCOWNLSUDK-UHFFFAOYSA-N Iodochlorine Chemical compound ICl QZRGKCOWNLSUDK-UHFFFAOYSA-N 0.000 description 12
235000011114 ammonium hydroxide Nutrition 0.000 description 12
150000002148 esters Chemical class 0.000 description 12
239000000908 ammonium hydroxide Substances 0.000 description 11
239000007864 aqueous solution Substances 0.000 description 11
239000003054 catalyst Substances 0.000 description 11
239000007787 solid Substances 0.000 description 11
239000002904 solvent Substances 0.000 description 11
OPWOOJXMCCDQFR-UHFFFAOYSA-N 3-acetamido-5-carbamoyl-2,4,6-triiodobenzoic acid Chemical compound CC(=O)NC1=C(I)C(C(N)=O)=C(I)C(C(O)=O)=C1I OPWOOJXMCCDQFR-UHFFFAOYSA-N 0.000 description 10
230000002378 acidificating effect Effects 0.000 description 10
239000011541 reaction mixture Substances 0.000 description 10
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
238000000354 decomposition reaction Methods 0.000 description 9
238000001990 intravenous administration Methods 0.000 description 9
KBZFDRWPMZESDI-UHFFFAOYSA-N 5-aminobenzene-1,3-dicarboxylic acid Chemical compound NC1=CC(C(O)=O)=CC(C(O)=O)=C1 KBZFDRWPMZESDI-UHFFFAOYSA-N 0.000 description 8
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
230000001154 acute effect Effects 0.000 description 8
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 8
AKXKBAWZIVNNJR-UHFFFAOYSA-N 3-amino-2,4,6-triiodo-5-(methylcarbamoyl)benzoic acid Chemical compound CNC(=O)C1=C(I)C(N)=C(I)C(C(O)=O)=C1I AKXKBAWZIVNNJR-UHFFFAOYSA-N 0.000 description 7
241000282472 Canis lupus familiaris Species 0.000 description 7
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
241000699670 Mus sp. Species 0.000 description 7
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 7
239000013078 crystal Substances 0.000 description 7
229910052739 hydrogen Inorganic materials 0.000 description 7
239000001257 hydrogen Substances 0.000 description 7
239000002002 slurry Substances 0.000 description 7
VNGWFWZSANAXPG-UHFFFAOYSA-N 3-(butanoylamino)-2,4,6-triiodo-5-(methylcarbamoyl)benzoic acid Chemical compound CCCC(=O)NC1=C(I)C(C(O)=O)=C(I)C(C(=O)NC)=C1I VNGWFWZSANAXPG-UHFFFAOYSA-N 0.000 description 6
BDXFKMQTIGVLEU-UHFFFAOYSA-N 3-carbamoyl-5-nitrobenzoic acid Chemical compound NC(=O)C1=CC(C(O)=O)=CC([N+]([O-])=O)=C1 BDXFKMQTIGVLEU-UHFFFAOYSA-N 0.000 description 6
SHWNNYZBHZIQQV-UHFFFAOYSA-J EDTA monocalcium diisodium salt Chemical compound [Na+].[Na+].[Ca+2].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O SHWNNYZBHZIQQV-UHFFFAOYSA-J 0.000 description 6
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
239000001201 calcium disodium ethylene diamine tetra-acetate Substances 0.000 description 6
235000011188 calcium disodium ethylene diamine tetraacetate Nutrition 0.000 description 6
239000002872 contrast media Substances 0.000 description 6
210000003734 kidney Anatomy 0.000 description 6
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 6
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
RNIZBMPNBRVVCU-UHFFFAOYSA-N 3-acetamido-5-(dimethylcarbamoyl)-2,4,6-triiodobenzoic acid Chemical compound CN(C)C(=O)C1=C(I)C(NC(C)=O)=C(I)C(C(O)=O)=C1I RNIZBMPNBRVVCU-UHFFFAOYSA-N 0.000 description 5
VIQDBCVNYLQYBN-UHFFFAOYSA-N 3-carbamoyl-5-(hexanoylamino)-2,4,6-triiodobenzoic acid Chemical compound C(CCCCC)(=O)NC=1C(=C(C(=C(C(=O)O)C1I)I)C(=O)N)I VIQDBCVNYLQYBN-UHFFFAOYSA-N 0.000 description 5
YVPYQUNUQOZFHG-UHFFFAOYSA-N amidotrizoic acid Chemical compound CC(=O)NC1=C(I)C(NC(C)=O)=C(I)C(C(O)=O)=C1I YVPYQUNUQOZFHG-UHFFFAOYSA-N 0.000 description 5
238000009903 catalytic hydrogenation reaction Methods 0.000 description 5
238000004090 dissolution Methods 0.000 description 5
150000004820 halides Chemical class 0.000 description 5
230000007062 hydrolysis Effects 0.000 description 5
238000006460 hydrolysis reaction Methods 0.000 description 5
DQTOZIJNMYYCJE-UHFFFAOYSA-N methyl 3-carbonochloridoyl-5-nitrobenzoate Chemical compound COC(=O)C1=CC(C(Cl)=O)=CC([N+]([O-])=O)=C1 DQTOZIJNMYYCJE-UHFFFAOYSA-N 0.000 description 5
150000004702 methyl esters Chemical class 0.000 description 5
235000019799 monosodium phosphate Nutrition 0.000 description 5
AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 5
239000000126 substance Substances 0.000 description 5
SUCSXOBLUWYMIG-UHFFFAOYSA-N 2,4,6-triiodo-3-(methylcarbamoyl)-5-(propanoylamino)benzoic acid Chemical compound CCC(=O)NC1=C(I)C(C(O)=O)=C(I)C(C(=O)NC)=C1I SUCSXOBLUWYMIG-UHFFFAOYSA-N 0.000 description 4
VUYKOUGVJQKFLO-UHFFFAOYSA-N 3-(dimethylcarbamoyl)-5-nitrobenzoic acid Chemical compound CN(C)C(=O)C1=CC(C(O)=O)=CC([N+]([O-])=O)=C1 VUYKOUGVJQKFLO-UHFFFAOYSA-N 0.000 description 4
MEEIUFXPBUXITI-UHFFFAOYSA-N 3-acetamido-5-(ethylcarbamoyl)-2,4,6-triiodobenzoic acid Chemical compound CCNC(=O)C1=C(I)C(NC(C)=O)=C(I)C(C(O)=O)=C1I MEEIUFXPBUXITI-UHFFFAOYSA-N 0.000 description 4
XHLMMVDCYIXUAX-UHFFFAOYSA-N 3-amino-5-carbamoylbenzoic acid Chemical compound NC(=O)C1=CC(N)=CC(C(O)=O)=C1 XHLMMVDCYIXUAX-UHFFFAOYSA-N 0.000 description 4
WIVDXBODHLGPKH-UHFFFAOYSA-N 3-carbamoyl-2,4,6-triiodo-5-(propanoylamino)benzoic acid Chemical compound IC1=C(C(=O)O)C(=C(C(=C1C(=O)N)I)NC(CC)=O)I WIVDXBODHLGPKH-UHFFFAOYSA-N 0.000 description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 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 4
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
229940039231 contrast media Drugs 0.000 description 4
238000001816 cooling Methods 0.000 description 4
229960005223 diatrizoic acid Drugs 0.000 description 4
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 4
229910000403 monosodium phosphate Inorganic materials 0.000 description 4
239000012452 mother liquor Substances 0.000 description 4
ZCRNIIJXDRYWDU-UHFFFAOYSA-N 3-(methoxycarbonyl)-5-nitrobenzoic acid Chemical compound COC(=O)C1=CC(C(O)=O)=CC([N+]([O-])=O)=C1 ZCRNIIJXDRYWDU-UHFFFAOYSA-N 0.000 description 3
GVKLFFIPALKQFM-UHFFFAOYSA-N 3-(methylcarbamoyl)-5-nitrobenzoic acid Chemical compound CNC(=O)C1=CC(C(O)=O)=CC([N+]([O-])=O)=C1 GVKLFFIPALKQFM-UHFFFAOYSA-N 0.000 description 3
VTHWFOOFHRZZDH-UHFFFAOYSA-N 3-amino-5-(dimethylcarbamoyl)benzoic acid Chemical compound CN(C(=O)C=1C=C(C=C(C1)C(=O)O)N)C VTHWFOOFHRZZDH-UHFFFAOYSA-N 0.000 description 3
SIIWAVHOCVSSKA-UHFFFAOYSA-N 3-amino-5-(methylcarbamoyl)benzoic acid Chemical compound CNC(=O)C1=CC(N)=CC(C(O)=O)=C1 SIIWAVHOCVSSKA-UHFFFAOYSA-N 0.000 description 3
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
241001465754 Metazoa Species 0.000 description 3
150000003863 ammonium salts Chemical class 0.000 description 3
238000010171 animal model Methods 0.000 description 3
239000003638 chemical reducing agent Substances 0.000 description 3
230000000052 comparative effect Effects 0.000 description 3
239000004615 ingredient Substances 0.000 description 3
239000000463 material Substances 0.000 description 3
FNYAWWIWBIZMRK-UHFFFAOYSA-N methyl 3-(dimethylcarbamoyl)-5-nitrobenzoate Chemical compound COC(=O)C1=CC(C(=O)N(C)C)=CC([N+]([O-])=O)=C1 FNYAWWIWBIZMRK-UHFFFAOYSA-N 0.000 description 3
229910052763 palladium Inorganic materials 0.000 description 3
239000011734 sodium Substances 0.000 description 3
229910052708 sodium Inorganic materials 0.000 description 3
ZEYOIOAKZLALAP-UHFFFAOYSA-M sodium amidotrizoate Chemical compound [Na+].CC(=O)NC1=C(I)C(NC(C)=O)=C(I)C(C([O-])=O)=C1I ZEYOIOAKZLALAP-UHFFFAOYSA-M 0.000 description 3
229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
235000017557 sodium bicarbonate Nutrition 0.000 description 3
238000007487 urography Methods 0.000 description 3
OBVKLPLBXFITOD-UHFFFAOYSA-N 3-(butanoylamino)-2,4,6-triiodo-5-(pentylcarbamoyl)benzoic acid Chemical compound CCCCCNC(=O)C1=C(I)C(NC(=O)CCC)=C(I)C(C(O)=O)=C1I OBVKLPLBXFITOD-UHFFFAOYSA-N 0.000 description 2
SLGLPCPQENJRPF-UHFFFAOYSA-N 3-(hexanoylamino)-2,4,6-triiodo-5-(methylcarbamoyl)benzoic acid Chemical compound CCCCCC(=O)NC1=C(I)C(C(O)=O)=C(I)C(C(=O)NC)=C1I SLGLPCPQENJRPF-UHFFFAOYSA-N 0.000 description 2
XRXDPWSLZBCKTC-UHFFFAOYSA-N 3-amino-5-(dimethylcarbamoyl)-2,4,6-triiodobenzoic acid Chemical compound CN(C)C(=O)C1=C(I)C(N)=C(I)C(C(O)=O)=C1I XRXDPWSLZBCKTC-UHFFFAOYSA-N 0.000 description 2
CTPQUDHURPLOBA-UHFFFAOYSA-N 3-amino-5-(ethylcarbamoyl)-2,4,6-triiodobenzoic acid Chemical compound CCNC(=O)C1=C(I)C(N)=C(I)C(C(O)=O)=C1I CTPQUDHURPLOBA-UHFFFAOYSA-N 0.000 description 2
JMICMRYYTAZIIB-UHFFFAOYSA-N 4-amino-2-carbamoylbenzoic acid Chemical compound NC1=CC=C(C(C(=O)N)=C1)C(=O)O JMICMRYYTAZIIB-UHFFFAOYSA-N 0.000 description 2
JEZJSNULLBSYHV-UHFFFAOYSA-N 5-amino-2,4,6-triiodobenzene-1,3-dicarboxylic acid Chemical compound NC1=C(I)C(C(O)=O)=C(I)C(C(O)=O)=C1I JEZJSNULLBSYHV-UHFFFAOYSA-N 0.000 description 2
JLLYLQLDYORLBB-UHFFFAOYSA-N 5-bromo-n-methylthiophene-2-sulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(Br)S1 JLLYLQLDYORLBB-UHFFFAOYSA-N 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
NWXKWMTUEDULJL-UHFFFAOYSA-N I(Cl)Cl.[K] Chemical compound I(Cl)Cl.[K] NWXKWMTUEDULJL-UHFFFAOYSA-N 0.000 description 2
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
CFMCNJJPUGYROW-UHFFFAOYSA-N NC=1C=C(C=C(C(=O)O)C1)C(=O)NCC Chemical compound NC=1C=C(C=C(C(=O)O)C1)C(=O)NCC CFMCNJJPUGYROW-UHFFFAOYSA-N 0.000 description 2
DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 2
239000003929 acidic solution Substances 0.000 description 2
230000010933 acylation Effects 0.000 description 2
238000005917 acylation reaction Methods 0.000 description 2
150000003973 alkyl amines Chemical class 0.000 description 2
125000003277 amino group Chemical group 0.000 description 2
239000008280 blood Substances 0.000 description 2
210000004369 blood Anatomy 0.000 description 2
239000000872 buffer Substances 0.000 description 2
DVECBJCOGJRVPX-UHFFFAOYSA-N butyryl chloride Chemical compound CCCC(Cl)=O DVECBJCOGJRVPX-UHFFFAOYSA-N 0.000 description 2
IQFVPQOLBLOTPF-HKXUKFGYSA-L congo red Chemical compound [Na+].[Na+].C1=CC=CC2=C(N)C(/N=N/C3=CC=C(C=C3)C3=CC=C(C=C3)/N=N/C3=C(C4=CC=CC=C4C(=C3)S([O-])(=O)=O)N)=CC(S([O-])(=O)=O)=C21 IQFVPQOLBLOTPF-HKXUKFGYSA-L 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
230000008025 crystallization Effects 0.000 description 2
150000005690 diesters Chemical class 0.000 description 2
239000006185 dispersion Substances 0.000 description 2
LVDRWEUVTPWUFK-UHFFFAOYSA-N ethyl 3-acetamido-2,4,6-triiodo-5-(methylcarbamoyl)benzoate Chemical compound CCOC(=O)C1=C(I)C(NC(C)=O)=C(I)C(C(=O)NC)=C1I LVDRWEUVTPWUFK-UHFFFAOYSA-N 0.000 description 2
238000002474 experimental method Methods 0.000 description 2
230000002349 favourable effect Effects 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
238000005984 hydrogenation reaction Methods 0.000 description 2
231100000053 low toxicity Toxicity 0.000 description 2
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 2
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 2
MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 description 2
229960002216 methylparaben Drugs 0.000 description 2
125000000896 monocarboxylic acid group Chemical group 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
239000003755 preservative agent Substances 0.000 description 2
230000002335 preservative effect Effects 0.000 description 2
238000000746 purification Methods 0.000 description 2
229910000029 sodium carbonate Inorganic materials 0.000 description 2
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 2
229910000162 sodium phosphate Inorganic materials 0.000 description 2
239000003381 stabilizer Substances 0.000 description 2
239000007858 starting material Substances 0.000 description 2
239000000725 suspension Substances 0.000 description 2
231100000057 systemic toxicity Toxicity 0.000 description 2
238000012360 testing method Methods 0.000 description 2
238000004448 titration Methods 0.000 description 2
231100000419 toxicity Toxicity 0.000 description 2
230000001988 toxicity Effects 0.000 description 2
OIXRDAZPDINJPT-UHFFFAOYSA-N 2,4,6-triiodo-3,5-bis(propanoylamino)benzoic acid Chemical compound CCC(=O)NC1=C(I)C(NC(=O)CC)=C(I)C(C(O)=O)=C1I OIXRDAZPDINJPT-UHFFFAOYSA-N 0.000 description 1
MMJYFEBZBADSNQ-UHFFFAOYSA-N 2-(dimethylcarbamoyl)benzoic acid Chemical compound CN(C)C(=O)C1=CC=CC=C1C(O)=O MMJYFEBZBADSNQ-UHFFFAOYSA-N 0.000 description 1
MOMFXATYAINJML-UHFFFAOYSA-N 2-Acetylthiazole Chemical group CC(=O)C1=NC=CS1 MOMFXATYAINJML-UHFFFAOYSA-N 0.000 description 1
DYYQMIIGYMNCSC-UHFFFAOYSA-N 3-(ethylcarbamoyl)-5-nitrobenzoic acid Chemical compound C(C)NC(C=1C=C(C(=O)O)C=C(C1)[N+](=O)[O-])=O DYYQMIIGYMNCSC-UHFFFAOYSA-N 0.000 description 1
MYWMLEMKOKPNAP-UHFFFAOYSA-N 5-acetamido-2,4,6-triiodobenzene-1,3-dicarboxylic acid Chemical compound CC(=O)NC1=C(I)C(C(O)=O)=C(I)C(C(O)=O)=C1I MYWMLEMKOKPNAP-UHFFFAOYSA-N 0.000 description 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
230000021736 acetylation Effects 0.000 description 1
238000006640 acetylation reaction Methods 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
150000001266 acyl halides Chemical class 0.000 description 1
230000001476 alcoholic effect Effects 0.000 description 1
235000019270 ammonium chloride Nutrition 0.000 description 1
238000002583 angiography Methods 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
239000007900 aqueous suspension Substances 0.000 description 1
230000004888 barrier function Effects 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
230000008499 blood brain barrier function Effects 0.000 description 1
210000001218 blood-brain barrier Anatomy 0.000 description 1
238000009835 boiling Methods 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000006227 byproduct Substances 0.000 description 1
150000001768 cations Chemical class 0.000 description 1
239000003610 charcoal Substances 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
239000011928 denatured alcohol Substances 0.000 description 1
230000008021 deposition Effects 0.000 description 1
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
DENRZWYUOJLTMF-UHFFFAOYSA-N diethyl sulfate Chemical compound CCOS(=O)(=O)OCC DENRZWYUOJLTMF-UHFFFAOYSA-N 0.000 description 1
229940008406 diethyl sulfate Drugs 0.000 description 1
238000007865 diluting Methods 0.000 description 1
GGTSJKFPGKFLCZ-UHFFFAOYSA-N dimethyl 5-nitrobenzene-1,3-dicarboxylate Chemical compound COC(=O)C1=CC(C(=O)OC)=CC([N+]([O-])=O)=C1 GGTSJKFPGKFLCZ-UHFFFAOYSA-N 0.000 description 1
VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 description 1
230000000694 effects Effects 0.000 description 1
125000004185 ester group Chemical group 0.000 description 1
IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
125000004494 ethyl ester group Chemical group 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
239000012021 ethylating agents‎ Substances 0.000 description 1
238000011156 evaluation Methods 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
239000012065 filter cake Substances 0.000 description 1
238000001914 filtration Methods 0.000 description 1
230000008570 general process Effects 0.000 description 1
239000011874 heated mixture Substances 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
239000005457 ice water Substances 0.000 description 1
238000002329 infrared spectrum Methods 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
239000000543 intermediate Substances 0.000 description 1
238000011835 investigation Methods 0.000 description 1
230000026045 iodination Effects 0.000 description 1
238000006192 iodination reaction Methods 0.000 description 1
210000003141 lower extremity Anatomy 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
239000011707 mineral Substances 0.000 description 1
PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
DPBLXKKOBLCELK-UHFFFAOYSA-N pentan-1-amine Chemical compound CCCCCN DPBLXKKOBLCELK-UHFFFAOYSA-N 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000012264 purified product Substances 0.000 description 1
230000005855 radiation Effects 0.000 description 1
239000012429 reaction media Substances 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
238000001226 reprecipitation Methods 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
WCIMWHNSWLLELS-UHFFFAOYSA-M sodium;3-acetamido-2,4,6-triiodo-5-(methylcarbamoyl)benzoate Chemical compound [Na+].CNC(=O)C1=C(I)C(NC(C)=O)=C(I)C(C([O-])=O)=C1I WCIMWHNSWLLELS-UHFFFAOYSA-M 0.000 description 1
230000002485 urinary effect Effects 0.000 description 1
239000008096 xylene Substances 0.000 description 1
239000011701 zinc Substances 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/04—X-ray contrast preparations
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/49—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups
- C07C205/57—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/12—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by halogen atoms or by nitro or nitroso groups

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Epidemiology (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
Medicinal Chemistry (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

CH990261A 1960-08-25 1961-08-24 Verfahren zur Herstellung von 5-Acylamino-2,4,6-trijodisophthalsäureamiden CH424751A (de)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
US5178660A	1960-08-25	1960-08-25
US119287A US3145197A (en)	1961-06-26	1961-06-26	5-acetamido-nu-alkyl-2, 4, 6-trhodoiso-phthalamic acid compounds
US12138861A	1961-07-03	1961-07-03
US12537361A	1961-07-20	1961-07-20

Publications (1)

Publication Number	Publication Date
CH424751A true CH424751A (de)	1966-11-30

Family

ID=27489435

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CH990261A CH424751A (de)	1960-08-25	1961-08-24	Verfahren zur Herstellung von 5-Acylamino-2,4,6-trijodisophthalsäureamiden

Country Status (6)

Country	Link
BE (1)	BE607551A (fr)
CH (1)	CH424751A (fr)
DE (1)	DE1443297C3 (fr)
ES (1)	ES270024A1 (fr)
FR (1)	FR1589M (fr)
GB (1)	GB994215A (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JP4801661B2 (ja) *	2005-03-18	2011-10-26	マナック株式会社	５−アミノ−２，４，６−トリヨードイソフタル酸誘導体のアセチル化方法

1961
- 1961-08-18 GB GB29941/61A patent/GB994215A/en not_active Expired
- 1961-08-21 ES ES0270024A patent/ES270024A1/es not_active Expired
- 1961-08-22 DE DE1443297A patent/DE1443297C3/de not_active Expired
- 1961-08-24 CH CH990261A patent/CH424751A/de unknown
- 1961-08-25 BE BE607551A patent/BE607551A/fr unknown
- 1961-11-09 FR FR878387A patent/FR1589M/fr not_active Expired

Also Published As

Publication number	Publication date
GB994215A (en)	1965-06-02
DE1443297B2 (de)	1974-08-29
DE1443297A1 (de)	1972-01-13
BE607551A (fr)	1962-02-26
FR1589M (fr)	1962-11-26
DE1443297C3 (de)	1975-04-17
ES270024A1 (es)	1962-01-01

Publication	Publication Date	Title
EP0015867B1 (fr)	1982-05-19	Diamides d'acides triiodo-isophtaliques, leur préparation et agents de contraste radiographiques les contenant
EP0308364B1 (fr)	1993-11-10	Acides bis(3,5-dicarbamoyl-2-4-6-triiodanilide) ou carboxyliques, leur procédé de préparation ainsi que les agents de contraste aux rayons X qui les contiennent
DE2523567C2 (de)	1983-01-05	2,4,6-Trijodbenzoesäure-Derivate und deren Verwendung als Röntgenkontrastmittel
EP0032387B1 (fr)	1983-11-02	Dérivés non ioniques d'acide 2,4,6-triiodo-isophtalique substitué en position 5, procédé pour leur préparation et agents de contraste pour rayons-X les contenant
DE1493627C3 (de)	1975-07-10	Verfahren zur Herstellung von 3-Acylaminomethyl-S-acylamino^Ae-trijodbenzoesäuren, deren Salzen und Estern
DE2624153C2 (de)	1981-10-15	N,N'-acylamido-trijod-benzoylierte Alkylendiamine, Verfahren zu ihrer Herstellung und ihre Verwendung als Kontrastmittel für Röntgenaufnahmen
CH630064A5 (de)	1982-05-28	Verfahren zur herstellung von jodhaltigen isophthalamidderivaten.
DE2732825A1 (de)	1978-02-23	2,4,6-trijodbenzoesaeurederivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende roentgenkontrastmittel
US3622616A (en)	1971-11-23	New benzoic acid derivatives
US3145197A (en)	1964-08-18	5-acetamido-nu-alkyl-2, 4, 6-trhodoiso-phthalamic acid compounds
DE2050217A1 (de)	1972-04-06	Monomethylamino Verbindungen
EP0032388B1 (fr)	1983-10-05	Dérivés ioniques d'acide 2,4,6-triiodo-isophtalique substitués en position 5, procédé pour leur préparation et agents de contraste pour rayons-X les contenant
CH641766A5 (de)	1984-03-15	2,4,6-trijodbenzonitrilderivate sowie diese verbindungen enthaltende roentgenkontrastmittel.
DE1443297C3 (de)	1975-04-17	20.07.61 USA 125373 5-Amino-2,4,6-trijodisophthalamidsäurederivate Verfahren zu ihrer Herstellung und diese enthaltende Röntgenkontrastmittel Mallinckrodt Chemical Works, St. Louis, Mo. (V.St.A.)
US3290366A (en)	1966-12-06	5-amino-nu-alkyl-2, 4, 6-triiodoisophthalamic acid derivatives
DE2526848A1 (de)	1976-01-02	Substituierte 2,4,6-trijodisophthalamische saeuren, verfahren zu ihrer herstellung und diese verbindungen enthaltende roentgenkontrastmittel
DD205892A5 (de)	1984-01-11	Verfahren zur herstellung von in kontrastmitteln verwendbaren brom-verbindungen
CH616403A5 (en)	1980-03-31	Process for the preparation of 2,4,6-triodoisophthalamides which are readily soluble in water.
DE2528795C3 (de)	1978-08-10	2,4,6-trijod-5-methoxyacetamido-N-methylisophthalamische Säure, Verfahren zu ihrer Herstellung und ein Salz dieser Säure enthaltendes Röntgenkontrastmittel
AT209895B (de)	1960-06-25	Verfahren zur Herstellung von 3-Amino-2,4,6-trijodbenzoylverbindungen
DE1125587B (de)	1962-03-15	Roentgenkontrastmittel
DE2132614A1 (de)	1972-08-17	Jodierte N-Acyl-Derivate von aromatischen Amino-Carbonsaeuren
AT205170B (de)	1959-09-10	Verfahren zur Herstellung von in Wasser schwerlöslichen Salzen der Tetracycline
DE1493979C3 (de)	1976-08-26	Bis-(5-amino-2,4,6-trijod-N-alkylisophthalsäureamid) -Derivate von Dicarbonsäuren, deren Salze mit pharmazeutisch verwendbaren Kationen, Verfahren zur Herstellung dieser Verbindungen und diese enthaltende Röntgenkontrastmittel
AT334356B (de)	1976-01-10	Verfahren zum herstellen des neuen (l,d oder dl) -5-hydroxytryptophan- (l,d oder dl) -glutamats