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【结 构 式】

【分子编号】12100

【品名】ethyl 2-[3-(hydroxymethyl)-4-oxo-3,4-dihydro-1-phthalazinyl]acetate

【CA登记号】

【 分 子 式 】C13H14N2O4

【 分 子 量 】262.26524

【元素组成】C 59.54% H 5.38% N 10.68% O 24.4%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(VI)

Zopolrestat can be obtained by several different ways: 1) The reaction of 2-(4-oxo-3,4-dihydrophthalazin-1-yl)acetic acid ethyl ester (I) with 2-chloroacetonitrile by means of potassium tert-butoxide in DMF gives 2-[3-(cyanomethyl)-4-oxo-3,4-dihydrophthalazin-1-yl]acetic acid ethyl ester (II), which is cyclized with 2-amino-4-(trifluoromethyl)thiophenol (III) in refluxing ethanol yielding zopolrestat ethyl ester (IV). Finally, this compound is hydrolyzed with KOH in methanol/water/THF. 2) Compound (IV) can also be obtained by cyclization of (II) with 4-chloro-3-nitrobenzotrifluoride (V) in hot DMF saturated with H2S. 3) Compound (II) can also be obtained as follows: The reaction of phthalazine (I) with aqueous formaldehyde gives 2-[3-(hydroxymethyl)-4-oxo-3,4-dihydrophthalazin-1-yl]acetic acid ethyl ester (VI), which is treated with PBr3 in ethyl ether yielding the bromomethyl derivative (VII). Finally, this compound is treated with potassium cyanide and KI in acetone/water.

1 Mylari, B.L.; Zembrowski, W.J.; Synthesis of aldose reductase inhibitor, 3,4-dihydro-4-oxo-3-[[5-(trifluoromethyl)-2 14C benzothiazolyl]methyl]-1-phthalazineacetic acid. J Label Compd Radiopharm 1991, 29, 2, 143-8.
2 Mealy, N.; Prous, J.; Castaner, J.; Zopolrestat. Drugs Fut 1995, 20, 1, 33.
3 Mylari, B.L.; Zembrowski, W.J. (Pfizer Inc.); Preparation of oxophthalazinyl acetic acids having benzothiazole or other heterocyclic side chains. EP 0295051 .
4 Mylari, B.L.; Larson, E.R.; Zembrowski, W.J. (Pfizer Inc.); Heterocyclic oxophthalazinylacetic acids. EP 0222576; JP 1987114988; US 4939140 .
5 Siegel, T.W.; Aldinger, C.E.; Mylari, B.L.; Singleton, D.H.; Zembrowski, W.J.; Larson, E.R.; Beyer, T.A.; Dee, M.F.; Novel, potent aldose reductase inhibitors: 3,4-Dihydro-4-oxo-3-[[5-(trifluoromethyl)-2-benzothiazolyl]methyl]-1-phthalazine-acetic acid (zopolrestat) and congeners. J Med Chem 1991, 34, 1, 108-22.
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) 12095 ethyl 2-(4-oxo-3,4-dihydro-1-phthalazinyl)acetate; Ethyl 3,4-dihydro-4-oxo-1-phthalazineacetate 25947-13-1 C12H12N2O3 详情 详情
(II) 12096 ethyl 2-[3-(2-nitriloethyl)-4-oxo-3,4-dihydro-1-phthalazinyl]acetate C14H13N3O3 详情 详情
(III) 12097 2-Amino-4-(trifluoromethyl)benzenethiol; 2-Amino-4-(trifluoromethyl)phenylhydrosulfide C7H6F3NS 详情 详情
(IV) 12098 ethyl 2-(4-oxo-3-[[5-(trifluoromethyl)-1,3-benzothiazol-2-yl]methyl]-3,4-dihydro-1-phthalazinyl)acetate C21H16F3N3O3S 详情 详情
(V) 12099 4-Chloro-3-nitro-alpha,alpha,alpha-trifluorotoluene; 1-Chloro-2-nitro-4-(trifluoromethyl)benzene 121-17-5 C7H3ClF3NO2 详情 详情
(VI) 12100 ethyl 2-[3-(hydroxymethyl)-4-oxo-3,4-dihydro-1-phthalazinyl]acetate C13H14N2O4 详情 详情
(VII) 12101 ethyl 2-[3-(bromomethyl)-4-oxo-3,4-dihydro-1-phthalazinyl]acetate C13H13BrN2O3 详情 详情
Extended Information