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【结 构 式】

【分子编号】67873

【品名】benzyl 2-aminoacetate hydrochloride

【CA登记号】 

【 分 子 式 】C9H11NO2.HCl

【 分 子 量 】201.65252

【元素组成】C 53.61% H 6% Cl 17.58% N 6.95% O 15.87%

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:(X)

Cyclization of 4-phenoxyphthalic acid (I) with glycine (II) at 215 °C gives the phthalimide (III), which by esterification with MeOH and H2SO4 at reflux yields the methyl ester (IV). Subsequent rearrangement of the phthalimidoacetate (IV) by means of Na in BuOH at 97 °C, followed by flash chromatography provides the isoquinoline-2-carboxylate (V). Bromination of compound (V) using POBr3 and NaHCO3 in acetonitrile leads to butyl 8-bromo-3-hydroxy-6-phenoxyisoquinoline-2-carboxylate (VI), which by hydrolysis with NaOH in refluxing H2O/EtOH affords the carboxylic acid (VII). Substitution of bromine in intermediate (VII) using MeI and BuLi in THF at –78 °C, followed by alkylation with PhCH2Br by means of K2CO3 in refluxing acetone yields the 2-methyl isoquinoline (VIII). Ester hydrolysis of compound (VIII) using KOH in MeOH gives the corresponding carboxylic acid (IX), which is then activated with i-BuOCOCl and Et3N in CH2Cl2, followed by condensation with benzyl glycinate hydrochloride (X) to yield the benzyl ester (XI). Finally, compound (XI) is debenzylated with H2 over Pd/C in EtOAc/MeOH .

1 Arend, M.P., Flippin, L.A., Du, X., Ho, W.-B., Turtle, E.D., Guenzler-Pukall, V. (FibroGen, Inc.). Nitrogen-containing heteroaryl compounds and their use in increasing endogenous erythropoietin. WO 2004108681.
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) 67865 4-phenoxyphthalic acid   C14H10O5 详情 详情
(II) 20436 glycine 56-40-6 C2H5NO2 详情 详情
(III) 67866 2-(1,3-dioxo-5-phenoxyisoindolin-2-yl)acetic acid   C16H11NO5 详情 详情
(IV) 67867 methyl 2-(1,3-dioxo-5-phenoxyisoindolin-2-yl)acetate   C17H13NO5 详情 详情
(V) 67868 butyl 1,4-dihydroxy-6-phenoxyisoquinoline-3-carboxylate   C20H19NO5 详情 详情
(VI) 67869 butyl 1-bromo-4-hydroxy-6-phenoxyisoquinoline-3-carboxylate   C20H18BrNO4 详情 详情
(VII) 67870 1-bromo-4-hydroxy-6-phenoxyisoquinoline-3-carboxylic acid   C16H10BrNO4 详情 详情
(VIII) 67871 benzyl 4-(benzyloxy)-1-methyl-6-phenoxyisoquinoline-3-carboxylate   C31H25NO4 详情 详情
(IX) 67872 4-(benzyloxy)-1-methyl-6-phenoxyisoquinoline-3-carboxylic acid   C21H21NO4 详情 详情
(X) 67873 benzyl 2-aminoacetate hydrochloride   C9H11NO2.HCl 详情 详情
(XI) 67874 benzyl 2-(4-(benzyloxy)-1-methyl-6-phenoxyisoquinoline-3-carboxamido)acetate   C33H28N2O5 详情 详情
Extended Information