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【结 构 式】 
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【分子编号】10278 【品名】2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl chloride 【CA登记号】6780-38-7 |
【 分 子 式 】C10H6ClNO3 【 分 子 量 】223.61528 【元素组成】C 53.71% H 2.7% Cl 15.85% N 6.26% O 21.46% |
合成路线1
该中间体在本合成路线中的序号：(II)The reaction of 1,2-dimethyl-3-benzoyl-4-aminopyrrole (I) with phthalimidoacetyl chloride (II) by means of NaOH gives 1,2-dimethyl-3-benzoyl-4-(phthalimidoacetamido)pyrrole (III), which is cyclized by reaction with hydrazine in refluxing methanol.
| 【1】 Corsico, N.; Tarzia, G.; Fontanella, L.; Mariani, L.; 3,7-Dihydro-5-phenylpyrrolo[3,4-e][1,4]diazepin-2(1H)-ones. Synthesis and pharmaclogical properties. Eur J Med Chem - Chim Ther 1976, 11, 3, 217-220. |
| 【2】 Fontanella, L.; Mariani, L.; Tarzia, G.; Pharmacologically active pyrrolodiazepines. DE 2511599; FR 2264546; GB 1433103; JP 50135094; US 4022766; US 4022766 . |
| 【3】 Castaner, J.; Serradell, M.N.; Premazepam. Drugs Fut 1984, 9, 7, 520. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 34365 | N'-(2-ethylbenzoyl)-3-methoxybenzenecarbohydrazonamide | C17H19N3O2 | 详情 | 详情 | |
| (II) | 10278 | 2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl chloride | 6780-38-7 | C10H6ClNO3 | 详情 | 详情 |
| (III) | 34367 | N-(4-benzoyl-1,5-dimethyl-1H-pyrrol-3-yl)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetamide | C23H19N3O4 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)A new synthesis of adinazolam has been described: The condensation of phthaloyl-glycyl chloride (I) with 2-amino-5-chlorobenzophenone (II) in refluxing toluene gives 4-chloro-2-(phthaloylglycylamido)benzophenone (III), which is cyclized by means of hydrazine in refluxing ethanol yielding 7-chloro-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one (IV). The reaction of (IV) with P2S5 in hot pyridine affords the corresponding thione (V), which is finally cyclized with N,N-dimethylglycine hydrazide by means of triethylamine in refluxing butanol. The starting products (I) and (II) are obtained as follows: The reaction of N-(ethoxycarbonyl)phthalimide (VI) with glycine by means of Na2CO3 in water gives the N-phthaloylglycine (VII), which is then treated with refluxing SOCl2 to give (I). The protection of 2-amino-4-chlorobenzoic acid (VIII) with tosyl chloride gives the corresponding N-tosyl derivative (IX), which by reaction with refluxing SOCl2 is converted into the acyl chloride (X). Finally, this compound is submitted to a Friedel-Craft's condensation with benzene and AlCl3 to afford (II).
| 【1】 Johnson, T.D.; Hsi, R.S.P.; Carbon-14 labeled 1,4-benzodiazepines. 3. J Label Compd Radiopharm 1976, 12, 4, 613-619. |
| 【2】 Castaner, J.; Pento, J.T.; Blancafort, P.; Serradell, M.N.; Adinazolam. Drugs Fut 1983, 8, 2, 87. |
| 【3】 Stelzer, L.S.; Hsi, R.S.P.; Synthesis of adinazolam mesylate-multiply labeled with carbon-13 and deuterium. J Label Compd Radiopharm 1989, 26, 3, 287. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 13364 | Benzene | 71-43-2 | C6H6 | 详情 | 详情 | |
| 40924 | 2-(dimethylamino)acetohydrazide | 539-64-0 | C4H11N3O | 详情 | 详情 | |
| (I) | 10278 | 2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl chloride | 6780-38-7 | C10H6ClNO3 | 详情 | 详情 |
| (II) | 10279 | (2-Amino-5-chlorophenyl)(phenyl)methanone; 2-Amino-5-chlorobenzophenone | 719-59-5 | C13H10ClNO | 详情 | 详情 |
| (III) | 10280 | N-(2-Benzoyl-4-chlorophenyl)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetamide | C23H15ClN2O4 | 详情 | 详情 | |
| (IV) | 10281 | 7-Chloro-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one; 1,4-benzdiazepin-2-one-5-phenyl-7-chloro | 1088-11-5 | C15H11ClN2O | 详情 | 详情 |
| (V) | 10282 | 7-Chloro-5-phenyl-3H-1,4-benzodiazepin-2-ylhydrosulfide; 7-Chloro-5-phenyl-3H-1,4-benzodiazepine-2-thiol | C15H11ClN2S | 详情 | 详情 | |
| (VI) | 10283 | ethyl 1,3-dioxo-1,3-dihydro-2H-isoindole-2-carboxylate; N-Carbethoxyphthalimide | 22509-74-6 | C11H9NO4 | 详情 | 详情 |
| (VII) | 10284 | N-Phthaloylglycine; 2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)acetic acid | 4702-13-0 | C10H7NO4 | 详情 | 详情 |
| (VIII) | 10285 | 2-Amino-5-chlorobenzoic acid | 635-21-2 | C7H6ClNO2 | 详情 | 详情 |
| (IX) | 10286 | 5-Chloro-2-[[(4-methylphenyl)sulfonyl]amino]benzoic acid | C14H12ClNO4S | 详情 | 详情 | |
| (X) | 10287 | 5-Chloro-2-[[(4-methylphenyl)sulfonyl]amino]benzoyl chloride | C14H11Cl2NO3S | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(XI)The reaction of (III) with (XI) by means of pyridine in THF gives 1,3-dioxo-2-isoindolineacetic acid [[N-(2-benzoyl-4-chlorophenyl)-1,3-dioxo-2-isoindolineacetamido]methylene]hydrazide (XVI), which by cyclization by means of trifluoroacetic acid in refluxing toluene yields 5-chloro-2-[3-(phtalimidomethyl)-4H-1,2,4-triazol-4-yl-benzophenone (XVII). The reaction of (XVII) with N,N,N',N'-tetramethyldiaminomethane (A) by means of acetyl chloride in DMF affords 5-chloro-2-[3-[(dimethylamino)methyl-5-(phthalimidomethyl)-4H-1,2,4-triazol-4-yl]benzophenone (XVIII), which is finally cyclized by means of hydrazine in hot ethanol.
| 【1】 Gall, M.; Hester, J.B.; US 3957761 . |
| 【2】 Castaner, J.; Pento, J.T.; Blancafort, P.; Serradell, M.N.; Adinazolam. Drugs Fut 1983, 8, 2, 87. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 14349 | N,N,N,N-tetramethylmethanediamine; tetramethylmethylenediamine;bis(dimethylamino)methane; N-[(dimethylamino)methyl]-N,N-dimethylamine | 51-80-9 | C5H14N2 | 详情 | 详情 |
| (III) | 35937 | 3-amino-6-chloro-4-phenyl-3,4-dihydro-4-quinazolinol | C14H12ClN3O | 详情 | 详情 | |
| (XI) | 10278 | 2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl chloride | 6780-38-7 | C10H6ClNO3 | 详情 | 详情 |
| (XVI) | 35944 | N-(2-benzoyl-4-chlorophenyl)-N,N'-bis[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl]hydrazonoformamide | C34H22ClN5O7 | 详情 | 详情 | |
| (XVII) | 35945 | 2-[[4-(2-benzoyl-4-chlorophenyl)-4H-1,2,4-triazol-3-yl]methyl]-1H-isoindole-1,3(2H)-dione | C24H15ClN4O3 | 详情 | 详情 | |
| (XVIII) | 35946 | 2-([4-(2-benzoyl-4-chlorophenyl)-5-[(dimethylamino)methyl]-4H-1,2,4-triazol-3-yl]methyl)-1H-isoindole-1,3(2H)-dione | C27H22ClN5O3 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(VIII)In a different method, N-phthaloylglycine (VII) was obtained by melting a mixture of phthalic anhydride (V) and glycine (VI). Subsequent chlorination of (VII) using SOCl2 provided acid chloride (VIII). Condensation of (VIII) with the sodium derivative of the tricarboxylate compound (IX) gave the keto triester (X). Hydrogenolysis of the benzyl ester groups of (X), followed by decarboxylation in refluxing toluene, gave rise to delta-phthalimidolevulinic acid (XI). This was finally hydrolyzed to the title compound upon refluxing with 7 N HCl.
| 【1】 Neuberger, A.; Scott, J.J.; The synhtesis of delta-succinamidolaevulic acid and related compounds. J Chem Soc 1954, 1820. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (V) | 11900 | 2-Benzofuran-1,3-dione;1,2-Benzenedicarboxylic Anhydride;1,2-BENZENE DICARBOXYLIC ACID ANHYDRIDE;1,2-BENZENEDICARBONIC ACID, ANHYDRIDE;1,3-DIOXOPHTHALAN;1,3-ISOBENZOFURANDIONE;o-phthalic anhydride; Phthalic anhydride | 85-44-9 | C8H4O3 | 详情 | 详情 |
| (VI) | 20436 | glycine | 56-40-6 | C2H5NO2 | 详情 | 详情 |
| (VII) | 10284 | N-Phthaloylglycine; 2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)acetic acid | 4702-13-0 | C10H7NO4 | 详情 | 详情 |
| (VIII) | 10278 | 2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl chloride | 6780-38-7 | C10H6ClNO3 | 详情 | 详情 |
| (IX) | 59145 | tribenzyl 1,1,2-ethanetricarboxylate | C26H24O6 | 详情 | 详情 | |
| (X) | 59146 | tribenzyl 4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-3-oxo-1,2,2-butanetricarboxylate | C36H29NO9 | 详情 | 详情 | |
| (XI) | 59147 | 5-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-4-oxopentanoic acid | C13H11NO5 | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(VIII)The organozinc reagent (LXXIX) was prepared by treatment of [(1-ethoxycyclopropyl)oxy]trimethylsilane (LXXVIII) with ZnCl2. Palladium-catalyzed coupling of (LXXIX) to phthalimidoacetyl chloride (VIII) furnished ethyl phthalimodolevulinate (XLI), which was finally hydrolyzed as in precedent methods.
| 【1】 Wang, J.; Scott, A.I.; An efficient synthesis of delta-aminolevulinic acid (ALA) and its isotopomers. Tetrahedron Lett 1997, 38, 5, 739. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VIII) | 10278 | 2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl chloride | 6780-38-7 | C10H6ClNO3 | 详情 | 详情 |
| (XLI) | 59167 | ethyl 5-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-4-oxopentanoate | C15H15NO5 | 详情 | 详情 | |
| (LXXVIII) | 52291 | Cyclopropanone ethyl trimethylsilyl acetal; (1-Ethoxycyclopropoxy)trimethylsilane | C8H18O2Si | 详情 | 详情 | |
| (LXXIX) | 59200 | bis(3-ethoxy-3-oxopropyl)zinc | C10H18O4Zn | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(IV)The condensation of the labeled glycine (I) with phthalic anhydride (II) by heating at 160 C gives the labeled phthalimido acetic acid (III), which is treated with refluxing SOCl2 to yield the acyl chloride (IV). The condensation of (IV) with 3-iodopropionic acid ethyl ester (V) by means of the Zn/Cu couple and Pd(PPh3)4 in hot toluene affords the labeled 5-phthalimido-levulinate (VI), which is finally treated with refluxing 6N HCl to provide the target labeled aminolevulinic acid.
| 【1】 Iida, K.; Kajiwara, M.; Synthesis of 13C and 15N multilabeled 5-aminolevulinic acid. J Label Compd Radiopharm 2002, 45, 2, 139. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 20436 | glycine | 56-40-6 | C2H5NO2 | 详情 | 详情 |
| (I) | 61588 | GLYCINE-13C2-15N | C2H5NO2 | 详情 | 详情 | |
| (II) | 11900 | 2-Benzofuran-1,3-dione;1,2-Benzenedicarboxylic Anhydride;1,2-BENZENE DICARBOXYLIC ACID ANHYDRIDE;1,2-BENZENEDICARBONIC ACID, ANHYDRIDE;1,3-DIOXOPHTHALAN;1,3-ISOBENZOFURANDIONE;o-phthalic anhydride; Phthalic anhydride | 85-44-9 | C8H4O3 | 详情 | 详情 |
| (III) | 10284 | N-Phthaloylglycine; 2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)acetic acid | 4702-13-0 | C10H7NO4 | 详情 | 详情 |
| (III) | 61589 | 2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetic acid | C10H7NO4 | 详情 | 详情 | |
| (IV) | 10278 | 2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl chloride | 6780-38-7 | C10H6ClNO3 | 详情 | 详情 |
| (IV) | 61590 | 2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl chloride | C10H6ClNO3 | 详情 | 详情 | |
| (V) | 61591 | ethyl 3-iodopropanoate | C5H9IO2 | 详情 | 详情 | |
| (VI) | 59167 | ethyl 5-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-4-oxopentanoate | C15H15NO5 | 详情 | 详情 | |
| (VI) | 61592 | ethyl 5-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-4-oxopentanoate | C15H15NO5 | 详情 | 详情 |
合成路线7
该中间体在本合成路线中的序号：(IV)The condensation of phthalic anhydride (I) with glycine (II) by heating at 160 C gives 2-phthalimidoacetic acid (III), which is treated with refluxing SOCl2 to yield the acetyl chloride (IV). The condensation of (IV) with Meldrum's acid (V) by means of pyridine in dichloromethane, followed by a treatment with refluxing ethanol, affords 4-phthalimidoaetoacetic acid ethyl ester (VI), which is condensed with 1-13C-labeled 2-bromoacetic acid ethyl ester (VII) by means of NaH in dimethoxyethane to provide labeled 2-(2-phthalimidoacetyl)succinic acid diethyl ester (VIII). Finally, this compound is treated with HCl in refluxing acetic acid to give the target labeled aminolevulinic acid.
| 【1】 Kurumaya, K.; Okazaki, T.; Seido, N.; Akasaka, Y.; Kawajiri, Y.; Kajiwara, M.; Kondo, M.; Facile synthesis of delta-aminolevulinic acid (ALA) regioselectively labeled with 13C and direct observation of enzymatic transformation from ALA to porphobilinogen (PBG). J Label Compd Radiopharm 1989, 27, 2, 217. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 11900 | 2-Benzofuran-1,3-dione;1,2-Benzenedicarboxylic Anhydride;1,2-BENZENE DICARBOXYLIC ACID ANHYDRIDE;1,2-BENZENEDICARBONIC ACID, ANHYDRIDE;1,3-DIOXOPHTHALAN;1,3-ISOBENZOFURANDIONE;o-phthalic anhydride; Phthalic anhydride | 85-44-9 | C8H4O3 | 详情 | 详情 |
| (II) | 20436 | glycine | 56-40-6 | C2H5NO2 | 详情 | 详情 |
| (III) | 10284 | N-Phthaloylglycine; 2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)acetic acid | 4702-13-0 | C10H7NO4 | 详情 | 详情 |
| (IV) | 10278 | 2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl chloride | 6780-38-7 | C10H6ClNO3 | 详情 | 详情 |
| (V) | 14738 | Meldrum's acid; 2,2-dimethyl-1,3-dioxane-4,6-dione；Malonic acid cyclic isopropylidene ester | 2033-24-1 | C6H8O4 | 详情 | 详情 |
| (VI) | 61596 | ethyl 4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-3-oxobutanoate | C14H13NO5 | 详情 | 详情 | |
| (VII) | 16640 | Ethyl 2-bromoacetate; Ethyl bromoacetate | 105-36-2 | C4H7BrO2 | 详情 | 详情 |
| (VII) | 61597 | ethyl 2-bromoacetate | C4H7BrO2 | 详情 | 详情 | |
| (VIII) | 61598 | diethyl 2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl]succinate | C18H19NO7 | 详情 | 详情 | |
| (VIII) | 64690 | diethyl 2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl]succinate | C18H19NO7 | 详情 | 详情 |
合成路线8
该中间体在本合成路线中的序号：(IV)The condensation of phthalic anhydride (I) with 1-13C-labeled glycine (II) by heating at 160 C gives 2-phthalimidoacetic acid (III), which is treated with refluxing SOCl2 to yield the acetyl chloride (IV). The condensation of (IV) with Meldrum's acid (V) by means of pyridine in dichloromethane, followed by a treatment with refluxing ethanol affords 4-phthalimidoaetoacetic acid ethyl ester (VI). This compound is condensed with 2-bromoacetic acid ethyl ester (VII) by means of NaH in dimethoxyethane to provide labeled 2-(2-phthalimidoacetyl)succinic acid diethyl ester (VIII). Finally, the compound is treated with HCl in refluxing acetic acid to give the target labeled aminolevulinic acid.
| 【1】 Kurumaya, K.; Okazaki, T.; Seido, N.; Akasaka, Y.; Kawajiri, Y.; Kajiwara, M.; Kondo, M.; Facile synthesis of delta-aminolevulinic acid (ALA) regioselectively labeled with 13C and direct observation of enzymatic transformation from ALA to porphobilinogen (PBG). J Label Compd Radiopharm 1989, 27, 2, 217. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 11900 | 2-Benzofuran-1,3-dione;1,2-Benzenedicarboxylic Anhydride;1,2-BENZENE DICARBOXYLIC ACID ANHYDRIDE;1,2-BENZENEDICARBONIC ACID, ANHYDRIDE;1,3-DIOXOPHTHALAN;1,3-ISOBENZOFURANDIONE;o-phthalic anhydride; Phthalic anhydride | 85-44-9 | C8H4O3 | 详情 | 详情 |
| (II) | 20436 | glycine | 56-40-6 | C2H5NO2 | 详情 | 详情 |
| (II) | 61599 | glycine | C2H5NO2 | 详情 | 详情 | |
| (III) | 10284 | N-Phthaloylglycine; 2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)acetic acid | 4702-13-0 | C10H7NO4 | 详情 | 详情 |
| (III) | 61600 | 2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetic acid | C10H7NO4 | 详情 | 详情 | |
| (IV) | 10278 | 2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl chloride | 6780-38-7 | C10H6ClNO3 | 详情 | 详情 |
| (IV) | 61627 | 2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl chloride | C10H6ClNO3 | 详情 | 详情 | |
| (V) | 14738 | Meldrum's acid; 2,2-dimethyl-1,3-dioxane-4,6-dione；Malonic acid cyclic isopropylidene ester | 2033-24-1 | C6H8O4 | 详情 | 详情 |
| (VI) | 61596 | ethyl 4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-3-oxobutanoate | C14H13NO5 | 详情 | 详情 | |
| (VI) | 61628 | ethyl 4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-3-oxobutanoate | C14H13NO5 | 详情 | 详情 | |
| (VII) | 16640 | Ethyl 2-bromoacetate; Ethyl bromoacetate | 105-36-2 | C4H7BrO2 | 详情 | 详情 |
| (VIII) | 61629 | diethyl 2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl]succinate | C18H19NO7 | 详情 | 详情 | |
| (VIII) | 64690 | diethyl 2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl]succinate | C18H19NO7 | 详情 | 详情 |
合成路线9
该中间体在本合成路线中的序号：(IV)The condensation of phthalic anhydride (I) with glycine (II) by heating at 160 C gives 2-phthalimidoacetic acid (III), which is treated with refluxing SOCl2 to yield the acetyl chloride (IV). The condensation of (IV) with Meldrum's acid (V) by means of pyridine in dichloromethane, followed by a treatment with refluxing ethanol affords 4-phthalimidoaetoacetic acid ethyl ester (VI). This compound is condensed with 2-13C-labeled 2-bromoacetic acid ethyl ester (VII) by means of NaH in dimethoxyethane to provide labeled 2-(2-phthalimidoacetyl)succinic acid diethyl ester (VIII). Finally, this compound is treated with HCl in refluxing acetic acid to give the target labeled aminolevulinic acid.
| 【1】 Kurumaya, K.; Okazaki, T.; Seido, N.; Akasaka, Y.; Kawajiri, Y.; Kajiwara, M.; Kondo, M.; Facile synthesis of delta-aminolevulinic acid (ALA) regioselectively labeled with 13C and direct observation of enzymatic transformation from ALA to porphobilinogen (PBG). J Label Compd Radiopharm 1989, 27, 2, 217. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 11900 | 2-Benzofuran-1,3-dione;1,2-Benzenedicarboxylic Anhydride;1,2-BENZENE DICARBOXYLIC ACID ANHYDRIDE;1,2-BENZENEDICARBONIC ACID, ANHYDRIDE;1,3-DIOXOPHTHALAN;1,3-ISOBENZOFURANDIONE;o-phthalic anhydride; Phthalic anhydride | 85-44-9 | C8H4O3 | 详情 | 详情 |
| (II) | 20436 | glycine | 56-40-6 | C2H5NO2 | 详情 | 详情 |
| (III) | 10284 | N-Phthaloylglycine; 2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)acetic acid | 4702-13-0 | C10H7NO4 | 详情 | 详情 |
| (IV) | 10278 | 2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl chloride | 6780-38-7 | C10H6ClNO3 | 详情 | 详情 |
| (V) | 14738 | Meldrum's acid; 2,2-dimethyl-1,3-dioxane-4,6-dione；Malonic acid cyclic isopropylidene ester | 2033-24-1 | C6H8O4 | 详情 | 详情 |
| (VI) | 61596 | ethyl 4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-3-oxobutanoate | C14H13NO5 | 详情 | 详情 | |
| (VII) | 16640 | Ethyl 2-bromoacetate; Ethyl bromoacetate | 105-36-2 | C4H7BrO2 | 详情 | 详情 |
| (VII) | 61630 | ethyl 2-bromoacetate | C4H7BrO2 | 详情 | 详情 | |
| (VIII) | 61631 | diethyl 2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl]succinate | C18H19NO7 | 详情 | 详情 | |
| (VIII) | 64690 | diethyl 2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl]succinate | C18H19NO7 | 详情 | 详情 |
合成路线10
该中间体在本合成路线中的序号：(IV)The condensation of phthalic anhydride (I) with glycine (II) by heating at 160 C gives 2-phthalimidoacetic acid (III), which is treated with refluxing SOCl2 to yield the acetyl chloride (IV). The condensation of (IV) with 2-13C-labeled Meldrum's acid (V) by means of pyridine in dichloromethane, followed by a treatment with refluxing ethanol affords 4-phthalimidoaetoacetic acid ethyl ester (VI). This compound is condensed with 2-bromoacetic acid ethyl ester (VII) by means of NaH in dimethoxyethane to provide labeled 2-(2-phthalimidoacetyl)succinic acid diethyl ester (VIII). Finally, the ester is treated with HCl in refluxing acetic acid to give the target labeled aminolevulinic acid.
| 【1】 Kurumaya, K.; Okazaki, T.; Seido, N.; Akasaka, Y.; Kawajiri, Y.; Kajiwara, M.; Kondo, M.; Facile synthesis of delta-aminolevulinic acid (ALA) regioselectively labeled with 13C and direct observation of enzymatic transformation from ALA to porphobilinogen (PBG). J Label Compd Radiopharm 1989, 27, 2, 217. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 11900 | 2-Benzofuran-1,3-dione;1,2-Benzenedicarboxylic Anhydride;1,2-BENZENE DICARBOXYLIC ACID ANHYDRIDE;1,2-BENZENEDICARBONIC ACID, ANHYDRIDE;1,3-DIOXOPHTHALAN;1,3-ISOBENZOFURANDIONE;o-phthalic anhydride; Phthalic anhydride | 85-44-9 | C8H4O3 | 详情 | 详情 |
| (II) | 20436 | glycine | 56-40-6 | C2H5NO2 | 详情 | 详情 |
| (III) | 10284 | N-Phthaloylglycine; 2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)acetic acid | 4702-13-0 | C10H7NO4 | 详情 | 详情 |
| (IV) | 10278 | 2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl chloride | 6780-38-7 | C10H6ClNO3 | 详情 | 详情 |
| (V) | 14738 | Meldrum's acid; 2,2-dimethyl-1,3-dioxane-4,6-dione；Malonic acid cyclic isopropylidene ester | 2033-24-1 | C6H8O4 | 详情 | 详情 |
| (V) | 61632 | 2,2-dimethyl-1,3-dioxane-4,6-dione | C6H8O4 | 详情 | 详情 | |
| (VI) | 61596 | ethyl 4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-3-oxobutanoate | C14H13NO5 | 详情 | 详情 | |
| (VI) | 61633 | ethyl 4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-3-oxobutanoate | C14H13NO5 | 详情 | 详情 | |
| (VII) | 16640 | Ethyl 2-bromoacetate; Ethyl bromoacetate | 105-36-2 | C4H7BrO2 | 详情 | 详情 |
| (VIII) | 61634 | diethyl 2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl]succinate | C18H19NO7 | 详情 | 详情 | |
| (VIII) | 64690 | diethyl 2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl]succinate | C18H19NO7 | 详情 | 详情 |
合成路线11
该中间体在本合成路线中的序号：(V)The condensation of 2-methylquinolin-8-ol (I) with 2,6-dichloro-3-nitrobenzyl chloride (II) by means of NaH in DMF gives the corresponding benzyl ether (III), which is reduced with Fe and HCl in methanol/water to the aniline (IV). The acylation of (IV) with 2-phthalimidoacetyl chloride (V) by means of DMAP and pyridine yields the amide (VI), which is methylated at the amidic nitrogen with NaH and methyl iodide in DMF to the N-methylanilide (VII). Elimination of the phthalimido group of (VII) with hydrazine in refluxing ethanol affords the glycine anilide (VIII), which is acylated with the acrylic acid (IX) by means of 1-[3-dimethylamino)propyl]-3-ethylcarbodiimide (DECD) and HOBT in DMF. The intermediate substituted acrylic acid (IX) has been obtained by reaction of 6-acetamidopyridine-3-carbaldehyde (X) with malonic acid and pyridine in refluxing ethanol.
| 【1】 Oku, T.; Kayakiri, H.; Satoh, S.; Abe, Y.; Sawada, Y.; Inoue, T.; Tanaka, H. (Fujisawa Pharmaceutical Co., Ltd.); Pyridopyrimidones, quinolines and fused N-heterocycles as bradykinin antagonists. EP 0807105; JP 1998507764; WO 9613485 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 18598 | 2-methyl-8-quinolinol | 826-81-3 | C10H9NO | 详情 | 详情 |
| (II) | 18928 | 1,3-dichloro-2-(chloromethyl)-4-nitrobenzene | C7H4Cl3NO2 | 详情 | 详情 | |
| (III) | 18929 | 2,6-dichloro-3-nitrobenzyl 2-methyl-8-quinolinyl ether; 8-[(2,6-dichloro-3-nitrobenzyl)oxy]-2-methylquinoline | C17H12Cl2N2O3 | 详情 | 详情 | |
| (IV) | 18930 | 2,4-dichloro-3-[[(2-methyl-8-quinolinyl)oxy]methyl]phenylamine; 2,4-dichloro-3-[[(2-methyl-8-quinolinyl)oxy]methyl]aniline | C17H14Cl2N2O | 详情 | 详情 | |
| (V) | 10278 | 2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl chloride | 6780-38-7 | C10H6ClNO3 | 详情 | 详情 |
| (VI) | 18932 | N-(2,4-dichloro-3-[[(2-methyl-8-quinolinyl)oxy]methyl]phenyl)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetamide | C27H19Cl2N3O4 | 详情 | 详情 | |
| (VII) | 18599 | N-(2,4-dichloro-3-[[(2-methyl-8-quinolinyl)oxy]methyl]phenyl)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-methylacetamide | C28H21Cl2N3O4 | 详情 | 详情 | |
| (VIII) | 18600 | 2-amino-N-(2,4-dichloro-3-[[(2-methyl-8-quinolinyl)oxy]methyl]phenyl)-N-methylacetamide | C20H19Cl2N3O2 | 详情 | 详情 | |
| (IX) | 19304 | (E)-3-[6-(acetamido)-3-pyridinyl]-2-propenoic acid | C10H10N2O3 | 详情 | 详情 | |
| (X) | 26413 | N-(5-formyl-2-pyridinyl)acetamide | C8H8N2O2 | 详情 | 详情 | |
| (XI) | 12963 | Malonic acid | 141-82-2 | C3H4O4 | 详情 | 详情 |
合成路线12
该中间体在本合成路线中的序号：(IV)Protection of 2,4-dichloro-3-nitrobenzyl alcohol (I) with tert-butyldiphenylsilyl chloride (TBDPSCl) in the presence of imidazole in DMF provided silyl ether (II). Then, reduction of the nitro group with hydrazine, FeCl3, and carbon gave aniline (III), which was condensed with N-phthaloylglycyl chloride (IV) to afford glycinamide (V). Alkylation with iodomethane in the presence of NaH yielded N-methylaniline (VI) and, then, the silyl ether was deprotected with tetra-n-butylammonium fluoride to produce alcohol (VII). Treatment with methanesulfonyl chloride provided mesylate (VIII), which was coupled with quinolinol (IX) in the presence of NaH in DMF to give ether (X). Subsequent removal of the N-phthaloyl group with hydrazine hydrate yielded amine (XI).
| 【1】 Abe, Y.; Kayakiri, H.; Satoh, S.; Inoue, T.; Sawada, Y.; Inamura, N.; Asano, M.; Aramori, I.; Hatori, C.; Sawai, H.; Oku, T.; Tanaka, H.; A novel class of orally active non-peptide bradykinin B2 receptor antagonists. 3. Discovering bioisosteres of the imidazo[1,2-a]pyridine moiety. J Med Chem 1998, 41, 21, 4062. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 18590 | (2,6-dichloro-3-nitrophenyl)methanol | C7H5Cl2NO3 | 详情 | 详情 | |
| (II) | 18591 | tert-butyl[(2,6-dichloro-3-nitrobenzyl)oxy]diphenylsilane; tert-butyl(diphenyl)silyl 2,6-dichloro-3-nitrobenzyl ether | C23H23Cl2NO3Si | 详情 | 详情 | |
| (III) | 18592 | 3-([[tert-butyl(diphenyl)silyl]oxy]methyl)-2,4-dichlorophenylamine; 3-([[tert-butyl(diphenyl)silyl]oxy]methyl)-2,4-dichloroaniline | C23H25Cl2NOSi | 详情 | 详情 | |
| (IV) | 10278 | 2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl chloride | 6780-38-7 | C10H6ClNO3 | 详情 | 详情 |
| (V) | 18594 | N-[3-([[tert-butyl(diphenyl)silyl]oxy]methyl)-2,4-dichlorophenyl]-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetamide | C33H30Cl2N2O4Si | 详情 | 详情 | |
| (VI) | 18595 | N-[3-([[tert-butyl(diphenyl)silyl]oxy]methyl)-2,4-dichlorophenyl]-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-methylacetamide | C34H32Cl2N2O4Si | 详情 | 详情 | |
| (VII) | 18596 | N-[2,4-dichloro-3-(hydroxymethyl)phenyl]-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-methylacetamide | C18H14Cl2N2O4 | 详情 | 详情 | |
| (VIII) | 18597 | 2,6-dichloro-3-[[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl](methyl)amino]benzyl methanesulfonate | C19H16Cl2N2O6S | 详情 | 详情 | |
| (IX) | 18598 | 2-methyl-8-quinolinol | 826-81-3 | C10H9NO | 详情 | 详情 |
| (X) | 18599 | N-(2,4-dichloro-3-[[(2-methyl-8-quinolinyl)oxy]methyl]phenyl)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-methylacetamide | C28H21Cl2N3O4 | 详情 | 详情 | |
| (XI) | 18600 | 2-amino-N-(2,4-dichloro-3-[[(2-methyl-8-quinolinyl)oxy]methyl]phenyl)-N-methylacetamide | C20H19Cl2N3O2 | 详情 | 详情 |
合成路线13
该中间体在本合成路线中的序号：(X)The target FR-165649 has been obtained by condensation of cinnamic acid (V) with amine (XIII) using EDC and HOBt as coupling agents. The two intermediates (V) and (XIII) have been obtained as follows: 1) Wittig reaction of 4-formylbenzoic acid (I) and methyl (triphenylphosphoranylidene)acetate (II) in THF gave methyl 4-carboxycinnamate (III), which was converted into amide (IV) by reaction with methylamine hydrochloride in the presence of EDC and HOBt. Further hydrolysis of the ester group with NaOH provided 4-(methylcarbamoyl)cinnamic acid (V). 2) The alkylation of 8-hydroxy-2-methylquinoline (VI) with benzylic chloride (VII) in the presence of NaH and a catalytic amount of tetrabutylammonium iodide in DMF afforded ether (VIII). Subsequent reduction of the nitro group with iron powder and HCl in refluxing aqueous methanol gave amine (IX), which was coupled with phthalimidoacetyl chloride (X) in the presence of DMAP in a mixture of N-methylpyrrolidone and pyridine to yield amide (XI). Then, alkylation at the amide N with CH3I and NaH provided (XII), and further hydrazinolysis of the phthalimido group yielded the primary amine (XIII). Finally, the target amide was obtained by condensation of cinnamic acid (V) with amine (XIII) using EDC and HOBt as the coupling reagents.
| 【1】 Oku, T.; Kayakiri, H.; Satoh, S.; Abe, Y.; Sawada, Y.; Inoue, T.; Tanaka, H. (Fujisawa Pharmaceutical Co., Ltd.); Pyridopyrimidones, quinolines and fused N-heterocycles as bradykinin antagonists. EP 0807105; JP 1998507764; WO 9613485 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 18922 | 4-formylbenzoic acid | 619-66-9 | C8H6O3 | 详情 | 详情 |
| (II) | 14689 | Methyl (triphenylphosphoranylidene)acetate; (methoxycarbonylmethylene)triphenylphosphorane；Methyl 2-(triphenyl-lambda(5)-phosphanylidene)acetate | 2605-67-6 | C21H19O2P | 详情 | 详情 |
| (III) | 18924 | 4-[(E)-3-methoxy-3-oxo-1-propenyl]benzoic acid | C11H10O4 | 详情 | 详情 | |
| (IV) | 18925 | methyl (E)-3-[4-[(methylamino)carbonyl]phenyl]-2-propenoate | C12H13NO3 | 详情 | 详情 | |
| (V) | 18926 | (E)-3-[4-[(methylamino)carbonyl]phenyl]-2-propenoic acid | C11H11NO3 | 详情 | 详情 | |
| (VI) | 18598 | 2-methyl-8-quinolinol | 826-81-3 | C10H9NO | 详情 | 详情 |
| (VII) | 18928 | 1,3-dichloro-2-(chloromethyl)-4-nitrobenzene | C7H4Cl3NO2 | 详情 | 详情 | |
| (VIII) | 18929 | 2,6-dichloro-3-nitrobenzyl 2-methyl-8-quinolinyl ether; 8-[(2,6-dichloro-3-nitrobenzyl)oxy]-2-methylquinoline | C17H12Cl2N2O3 | 详情 | 详情 | |
| (IX) | 18930 | 2,4-dichloro-3-[[(2-methyl-8-quinolinyl)oxy]methyl]phenylamine; 2,4-dichloro-3-[[(2-methyl-8-quinolinyl)oxy]methyl]aniline | C17H14Cl2N2O | 详情 | 详情 | |
| (X) | 10278 | 2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl chloride | 6780-38-7 | C10H6ClNO3 | 详情 | 详情 |
| (XI) | 18932 | N-(2,4-dichloro-3-[[(2-methyl-8-quinolinyl)oxy]methyl]phenyl)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetamide | C27H19Cl2N3O4 | 详情 | 详情 | |
| (XII) | 18599 | N-(2,4-dichloro-3-[[(2-methyl-8-quinolinyl)oxy]methyl]phenyl)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-methylacetamide | C28H21Cl2N3O4 | 详情 | 详情 | |
| (XIII) | 18600 | 2-amino-N-(2,4-dichloro-3-[[(2-methyl-8-quinolinyl)oxy]methyl]phenyl)-N-methylacetamide | C20H19Cl2N3O2 | 详情 | 详情 |
合成路线14
该中间体在本合成路线中的序号：(VII)The reaction of 2,6-dichloro-3-nitrotoluene (I) with CuCN in hot DMF gives the benzonitrile (II), which is brominated with 1,3-dibromo-5,5-dimethylhidantoin (DBDH) and benzoyl peroxide in hot chlorobenzene yielding the benzyl bromide (III). The reaction of (III) with 2-methyl-8-quinolinol (IV) by means of K2CO3 or Cs2CO3 in DMF affords the benzyl ether (V), which is reduced at the nitro group with SnCl2 giving the amino derivative (VI). The condensation of (VI) with 2-phthalimidoacetyl chloride (VII) by means of DMAP and pyridine in refluxing dichloromethane yields the corresponding amide (VIII), which is N-methylated with methyl iodide and NaH in DMF affording intermediate (IX). Elimination of the phthalimido group of (IX) with hydrazine in refluxing dichloromethane/methanol provides the substituted glycinamide (X), which is finally acylated with 3-(3-methoxyphenyl)-2(E)-propenoyl chloride (XI) by means of triethylamine in refluxing dichloromethane.
| 【1】 Scholkens, B.A.; Heitsch, H.; Eagner, A.; Wirth, K.; Novel series of O-substituted 8-quinolines and 4-benzothiazoles as potent antagonists of the bradykinin B2 receptors. Bioorg Med Chem Lett 1999, 9, 3, 327. |
| 【2】 Heitsch, H.; Wirth, K.; Scholkens, B.; Wagner, A. (Aventis SA); Fused N-heterocyclic cpds. substd. with benzyloxy, process for their preparation and their use as bradykinin receptor antagonists. DE 19712960; EP 0867432; JP 1998279563 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 29524 | 1,3-dichloro-2-methyl-4-nitrobenzene | 29682-46-0 | C7H5Cl2NO2 | 详情 | 详情 |
| (II) | 29525 | 3-chloro-2-methyl-6-nitrobenzonitrile | C8H5ClN2O2 | 详情 | 详情 | |
| (III) | 29526 | 2-(bromomethyl)-3-chloro-6-nitrobenzonitrile | C8H4BrClN2O2 | 详情 | 详情 | |
| (IV) | 18598 | 2-methyl-8-quinolinol | 826-81-3 | C10H9NO | 详情 | 详情 |
| (V) | 29527 | 3-chloro-2-[[(2-methyl-8-quinolinyl)oxy]methyl]-6-nitrobenzonitrile | C18H12ClN3O3 | 详情 | 详情 | |
| (VI) | 29528 | 6-amino-3-chloro-2-[[(2-methyl-8-quinolinyl)oxy]methyl]benzonitrile | C18H14ClN3O | 详情 | 详情 | |
| (VII) | 10278 | 2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl chloride | 6780-38-7 | C10H6ClNO3 | 详情 | 详情 |
| (VIII) | 29529 | N-(4-chloro-2-cyano-3-[[(2-methyl-8-quinolinyl)oxy]methyl]phenyl)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetamide | C28H19ClN4O4 | 详情 | 详情 | |
| (IX) | 29530 | N-(4-chloro-2-cyano-3-[[(2-methyl-8-quinolinyl)oxy]methyl]phenyl)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-methylacetamide | C29H21ClN4O4 | 详情 | 详情 | |
| (X) | 29531 | 2-amino-N-(4-chloro-2-cyano-3-[[(2-methyl-8-quinolinyl)oxy]methyl]phenyl)-N-methylacetamide | C21H19ClN4O2 | 详情 | 详情 | |
| (XI) | 29532 | (E)-3-(3-methoxyphenyl)-2-propenoyl chloride | C10H9ClO2 | 详情 | 详情 |
合成路线15
该中间体在本合成路线中的序号：(II)The condensation of ethyl 2-cyano-3,3-dimethylthioacrylate (I) with S-methylisothiourea (II) in refluxing ethanol yielded pyrimidinone (V). Alternatively, the intermediate pyrimidinone (V) was obtained by condensation of 2-cyano-3,3-dimethylthioacrylamide (III) with anhydride (IV). Subsequent chlorination of (V) with refluxing phosphoryl chloride provided the title chloropyrimidine.
| 【1】 Upadyay, D.N.; Ram, V.J.; Shukla, P.K.; Raghywanshi, s.K.; Agarwal, N.; Suitably functionalised pyrimidines as potential antimycotic agents. Bioorg Med Chem Lett 2000, 10, 8, 703. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 22737 | methyl 2-cyano-3,3-bis(methylsulfanyl)acrylate | C7H9NO2S2 | 详情 | 详情 | |
| (II) | 10278 | 2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl chloride | 6780-38-7 | C10H6ClNO3 | 详情 | 详情 |
| (III) | 55361 | 2-cyano-3,3-bis(methylsulfanyl)acrylamide | C6H8N2OS2 | 详情 | 详情 | |
| (IV) | 55362 | C4H6O3S2 | 详情 | 详情 | ||
| (V) | 55363 | 2,4-bis(methylsulfanyl)-6-oxo-1,6-dihydro-5-pyrimidinecarbonitrile | C7H7N3OS2 | 详情 | 详情 |
合成路线16
该中间体在本合成路线中的序号：(X)Coupling between 4-nitrobenzoyl chloride (VI) and 4-aminobenzoic acid (VII) afforded nitrobenzamide (VIII), which was further reduced to amine (IX) by catalytic hydrogenation over Pd/C. Acylation of (IX) with phthalimidoacetyl chloride (X) yielded diamide (XI). The carboxyl group of (XI) was then activated as the corresponding acid chloride (XII) by treatment with SOCl2. Then, condensation of the glycylamide derivative (XIII) with acid chloride (XII) furnished amide (XIV).
| 【1】 Rousseaux, O.; Simonot, C. (Guerbet SA); Gadolinium complex tetramides and use in medical imaging. EP 1178975; FR 2793795; WO 0071526 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VI) | 18941 | p-nitrobenzoyl chloride; 4-nitrobenzoyl chloride | 122-04-3 | C7H4ClNO3 | 详情 | 详情 |
| (VII) | 20004 | p-aminobenzoic acid; 4-aminobenzoic acid | 150-13-0 | C7H7NO2 | 详情 | 详情 |
| (VIII) | 56045 | 4-[(4-nitrobenzoyl)amino]benzoic acid | C14H10N2O5 | 详情 | 详情 | |
| (IX) | 56046 | 4-[(4-aminobenzoyl)amino]benzoic acid | C14H12N2O3 | 详情 | 详情 | |
| (X) | 10278 | 2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl chloride | 6780-38-7 | C10H6ClNO3 | 详情 | 详情 |
| (XI) | 56047 | 4-[(4-{[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl]amino}benzoyl)amino]benzoic acid | C24H17N3O6 | 详情 | 详情 | |
| (XII) | 56048 | 4-[(4-{[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl]amino}benzoyl)amino]benzoyl chloride | C24H16ClN3O5 | 详情 | 详情 | |
| (XIII) | 56049 | 5-[(2-aminoacetyl)amino]-2,4,6-tribromo-N~1~,N~1~,N~3~,N~3~-tetrakis(2,3,4,5,6-pentahydroxyhexyl)isophthalamide | C34H57Br3N4O23 | 详情 | 详情 | |
| (XIV) | 56050 | 2,4,6-tribromo-5-{[2-({4-[(4-{[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl]amino}benzoyl)amino]benzoyl}amino)acetyl]amino}-N~1~,N~1~,N~3~,N~3~-tetrakis(2,3,4,5,6-pentahydroxyhexyl)isophthalamide | C58H72Br3N7O28 | 详情 | 详情 |