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【结 构 式】 
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【分子编号】10284 【品名】N-Phthaloylglycine; 2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)acetic acid 【CA登记号】4702-13-0 |
【 分 子 式 】C10H7NO4 【 分 子 量 】205.16992 【元素组成】C 58.54% H 3.44% N 6.83% O 31.19% |
合成路线1
该中间体在本合成路线中的序号：(VII)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2
该中间体在本合成路线中的序号：(VII)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3
该中间体在本合成路线中的序号：(III)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4
该中间体在本合成路线中的序号：(III)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5
该中间体在本合成路线中的序号：(III)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6
该中间体在本合成路线中的序号：(III)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7
该中间体在本合成路线中的序号：(III)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8
该中间体在本合成路线中的序号：(II)Acylation of ethyl 3-amino-2-(3,5-dimethoxyphenyl)propionate (I) with N-phthaloylglycine (II) using EDC and HOAt afforded amide (III), which was subjected to a Bischler-Napieralski cyclization in the presence of POCl3 to produce the dihydroisoquinoline (IV). Aromatization of (IV) to the corresponding isoquinoline (V) was achieved by treatment with MnO2 in refluxing benzene. Hydrazinolysis of the phthaloyl group of (V) gave the free amine, which was purified after conversion to the N-Boc derivative (VI). Acid cleavage of the Boc group then furnished the title product.
| 【1】 Coppola, G.M.; et al.; 1-Aminomethylisoquinoline-4-carboxylates as novel dipeptidylpeptidase IV inhibitors. Bioorg Med Chem Lett 2000, 10, 14, 1555. |
| 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) | 46959 | ethyl 3-amino-2-(3,5-dimethoxyphenyl)propanoate | C13H19NO4 | 详情 | 详情 | |
| (II) | 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) | 46960 | ethyl 2-(3,5-dimethoxyphenyl)-3-[[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl]amino]propanoate | C23H24N2O7 | 详情 | 详情 | |
| (IV) | 46961 | ethyl 1-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-6,8-dimethoxy-3,4-dihydro-4-isoquinolinecarboxylate | C23H22N2O6 | 详情 | 详情 | |
| (V) | 46962 | ethyl 1-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-6,8-dimethoxy-4-isoquinolinecarboxylate | C23H20N2O6 | 详情 | 详情 | |
| (VI) | 46963 | ethyl 1-[[(tert-butoxycarbonyl)amino]methyl]-6,8-dimethoxy-4-isoquinolinecarboxylate | C20H26N2O6 | 详情 | 详情 |