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【结 构 式】 
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【分子编号】58854 【品名】2-(2-hydroxyethyl)-1H-isoindole-1,3(2H)-dione;N-Hydroxyethylphthalimide;N-(2-Hydroxyethyl)phthalimide;2-(2-hydroxyethyl)isoindoline-1,3-dione 【CA登记号】3891-07-4 |
【 分 子 式 】C10H9NO3 【 分 子 量 】191.1864 【元素组成】C 62.82% H 4.74% N 7.33% O 25.11% |
与该中间体有关的原料药合成路线共 2 条
合成路线1
该中间体在本合成路线中的序号：(VI)Condensation of 7-hydroxy-4,8-dimethylcoumarin (I) with 3-chloro-2-butanone (II) affords the keto alkoxycoumarin (III), which is cyclized to the psoralen derivative (IV) under basic conditions. Benzylic bromination of (IV) by means of N-bromosuccinimide provides the bromomethyl compound (V) as the major isomer. Bromide (V) is then condensed with N-(2-hydroxyethyl)phthalimide (VI) to furnish ether (VII). The phthaloyl group of (VII) is removed by treatment with either primary amines or with hydrazine to produce the target free amine, which is finally isolated as the corresponding hydrochloride salt.
| 【1】 Wollowitz, S.; Isaacs, S.T.; Rapoport, H.; Spielmann, H.P. (Steritech, Inc.); Cpds. for the photodecontamination of pathogens in blood. US 5399719; WO 9500141 . |
| 【2】 Wollowitz, S.; Isaacs, S.T.; Rapoport, H.; Spielman, H.P.; Niero, A. (Steritech, Inc.); Cpds. for the photodecontamination of pathogens in blood. WO 9614739 . |
| 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) | 58850 | 4,8-Dimethyl-7-hydroxycoumarin | C11H10O3 | 详情 | 详情 | |
| (II) | 12423 | 3-Chloro-2-butanone | 4091-39-8 | C4H7ClO | 详情 | 详情 |
| (III) | 58851 | 4,8-dimethyl-7-(1-methyl-2-oxopropoxy)-2H-chromen-2-one | C15H16O4 | 详情 | 详情 | |
| (IV) | 58852 | 2,3,5,9-tetramethyl-7H-furo[3,2-g]chromen-7-one | C15H14O3 | 详情 | 详情 | |
| (V) | 58853 | 3-(bromomethyl)-2,5,9-trimethyl-7H-furo[3,2-g]chromen-7-one | C15H13BrO3 | 详情 | 详情 | |
| (VI) | 58854 | 2-(2-hydroxyethyl)-1H-isoindole-1,3(2H)-dione;N-Hydroxyethylphthalimide;N-(2-Hydroxyethyl)phthalimide;2-(2-hydroxyethyl)isoindoline-1,3-dione | 3891-07-4 | C10H9NO3 | 详情 | 详情 |
| (VII) | 58855 | 2-{2-[(2,5,9-trimethyl-7-oxo-7H-furo[3,2-g]chromen-3-yl)methoxy]ethyl}-1H-isoindole-1,3(2H)-dione | C25H21NO6 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)
| 【1】 Arrowsmith JE,Campbell SF,Cross PE,et al.Long-acting dihydropyridine calcium antagonists.1.2-Alkoxymethyl derivatives incorporating basic substituents.J Med Chem,1986,29:1696. |
| 【2】 Campbell SF,Cross PE,Stubbs JK.Dihydropyridine anti-ischemic and antihypertensive agents and pharmaceutical compositions containing them:EP,Patent 89,167,1983. |
| 【3】 Billman JH,Parker EE.Amino acids.I.Glycine.J Am Chem Soc,1943,65:761. |
| 【4】 Soine TO,Buchdahl MR.β-Bromoethylphalimide.Org Synth,1952,32:18. |
| 【5】 Peters THA,Benneker FBG,Slanina PBJ.Process for making amlodipine,derivatives thereof,and precursors thereof:US,Patent 2,002,143,046,2002. |
| 【6】 Alsan T,Adiyaman M,Yurdakul A,et al.Isolation of dihydropyridine derivative and preparation salts thereof:WO,Patent 2,004,058,711,2004. |
| 【7】 Bolugoddu V.Dahyabhai JL.Pingili RR.et al.Process for preparing amlodipine:US,Patent 2,007,260,065,2007. |
| 【8】 Purohit AK,Desai BC,Shete BD,et al.Process for the preparation of anti-ischemic and anti-hypertensive drug amlodipine besylate:US,Patent 2,004,044,218,2004. |
| 【9】 Davison E,Wells JI.Salts of amlodipine:DE,Patent 3,710,457,1987. |
| 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) | 58854 | 2-(2-hydroxyethyl)-1H-isoindole-1,3(2H)-dione;N-Hydroxyethylphthalimide;N-(2-Hydroxyethyl)phthalimide;2-(2-hydroxyethyl)isoindoline-1,3-dione | 3891-07-4 | C10H9NO3 | 详情 | 详情 |
| (III) | 44032 | Ethyl 4-(2-phthalimidoethoxy)acetoacetate;ETHYL4-[2-(1,3-DIOXO-1,3-DIHYDRO-2H-ISOINDOL-2-YL)ETHOXYL]-3-OXOBUTANOATE;Ethyl-4(2-Phthalimido Ethoxy)Acetoacetate;ethyl 4-(2-(1,3-dioxoisoindolin-2-yl)ethoxy)-3-oxobutanoate; Ethyl 4-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethoxy]-3-oxobutanoate | 88150-75-8 | C16H17NO6 | 详情 | 详情 |
| (IV) | 54215 | ethyl (Z)-3-(2-chlorophenyl)-2-{2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethoxy]acetyl}-2-propenoate | n/a | C23H20ClNO6 | 详情 | 详情 |
| (V) | 44035 | Phthalimido amlodipine; Phthaloyl Amlodipine; 3-Ethyl 5-methyl 4-(2-chlorophenyl)-2-[[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethoxy]methyl]-6-methyl-1,4-dihydro-3,5-pyridinedicarboxylate | 103094-30-0 | C28H27ClN2O7 | 详情 | 详情 |
| (VI) | 23541 | ethyl 4-chloro-3-oxobutanoate；Ethyl 4-chloro-3-oxobutanoate；Ethyl 4-chloroacetoacetate | 638-07-3 | C6H9ClO3 | 详情 | 详情 |
| (VII) | 24114 | 2-chlorobenzaldehyde | 89-98-5 | C7H5ClO | 详情 | 详情 |
| (VIII) | 10158 | Piperidine | 110-89-4 | C5H11N | 详情 | 详情 |
| (IX) | 69569 | Methyl 3-aminocrotonate;Methyl 3-amino-2-butenoate;(Z)-methyl 3-aminobut-2-enoate | 14205-39-1 | C5H9NO2 | 详情 | 详情 |
| (X) | 69570 | Benzenesulfonic acid;Phenylsulfonic acid;Benzenemonosulfonic acid;Benzensulfonic acid;Benzenesulphonic acid; | 98-11-3 | C6H6O3S | 详情 | 详情 |
Extended Information