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【结 构 式】

【分子编号】39281

【品名】2-propylpyridine

【CA登记号】622-39-9

【 分 子 式 】C8H11N

【 分 子 量 】121.18208

【元素组成】C 79.29% H 9.15% N 11.56%

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:(I)

The title compound has been prepared by two related procedures. Alkylation of 2-propylpyridine (I) with 4-methoxyphenacyl bromide (II) in refluxing acetone gave the pyridinum salt (III), which was further cyclized to the indolizine (IV) using aqueous NaHCO3. Condensation of (IV) with dimethyl acetylenedicarboxylate (V), followed by oxidation with 2,3-dichloro-5,6-dicyanoquinone furnished the tricyclic system (VI). Hydrolysis of the diester of (VI) and subsequent decarboxylation of the resulting diacid (VII) produced the methoxy derivative (VIII). Finally, demethylation of (VIII) using AlCl3 and ethanethiol gave rise to the title phenol compound.

1 Christiansen, L.B.; Kanstrup, A.; Jacobsen, P.; Jorgensen, A.S.; Bury, P.S. (Novo Nordisk A/S); Pyrrolo[2,1,5-cd]indolizine derivs. useful in the prevention or treatment of estrogen related diseases or syndromes. EP 0986560; US 6075036; WO 9855482 .
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) 39281 2-propylpyridine 622-39-9 C8H11N 详情 详情
(II) 21991 2-Methoxyphenacyl bromide; 2-bromo-1-(4-methoxyphenyl)-1-ethanone 2632-13-5 C9H9BrO2 详情 详情
(III) 39282 1-[2-(4-methoxyphenyl)-2-oxoethyl]-2-propylpyridinium bromide C17H20BrNO2 详情 详情
(IV) 39283 4-(1-ethyl-2-indolizinyl)phenyl methyl ether; 1-ethyl-2-(4-methoxyphenyl)indolizine C17H17NO 详情 详情
(V) 24551 Dimethyl acetylenedicarboxylate; Dimethyl 2-butynedioate;Acetylenedicarboxylic acid dimethyl ester 762-42-5 C6H6O4 详情 详情
(VI) 39284 dimethyl 4-ethyl-3-(4-methoxyphenyl)pyrrolo[2,1,5-cd]indolizine-1,2-dicarboxylate C23H21NO5 详情 详情
(VII) 39285 4-ethyl-3-(4-methoxyphenyl)pyrrolo[2,1,5-cd]indolizine-1,2-dicarboxylic acid C21H17NO5 详情 详情
(VIII) 39286 1-ethyl-2-(4-methoxyphenyl)pyrrolo[2,1,5-cd]indolizine; 4-(1-ethylpyrrolo[2,1,5-cd]indolizin-2-yl)phenyl methyl ether C19H17NO 详情 详情

合成路线2

该中间体在本合成路线中的序号:(I)

In a very close procedure, alkylation of 2-propylpyridine (I) was effected with 4-benzyloxyphenacyl bromide (IX). The resulting pyridinium salt (X) was cyclized with NaHCO3 to give (XI), which was then condensed with dimethyl acetylenedicarboxylate (V) as before to give the tricyclic system (XII). Hydrolysis of diester (XII) to diacid (XIII), followed by decarboxylation with copper in hot quinoline yielded (XIV). The benzyl protecting group of (XIV) was then removed by catalytic hydrogenolysis in the presence of Pd/C.

1 Wassermann, K.; Kanstrup, A.; Jorgensen, A.S.; Bain, S.; Naerum, L.; Jacobsen, P.; Christiansen, L.B.; Bury, P.S.; Thorpe, S.M.; Synthesis and pharmacology of a novel pyrrolo[2,1,5-cd] indolizine (NNC 45-0095), a high affinity non-steroidal agonist for the estrogen receptor. Bioorg Med Chem Lett 2000, 10, 4, 399.
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) 39281 2-propylpyridine 622-39-9 C8H11N 详情 详情
(V) 24551 Dimethyl acetylenedicarboxylate; Dimethyl 2-butynedioate;Acetylenedicarboxylic acid dimethyl ester 762-42-5 C6H6O4 详情 详情
(IX) 36424 1-[4-(benzyloxy)phenyl]-2-bromo-1-ethanone C15H13BrO2 详情 详情
(X) 39287 1-[2-[4-(benzyloxy)phenyl]-2-oxoethyl]-2-propylpyridinium bromide C23H24BrNO2 详情 详情
(XI) 39288 benzyl 4-(1-ethyl-2-indolizinyl)phenyl ether; 2-[4-(benzyloxy)phenyl]-1-ethylindolizine C23H21NO 详情 详情
(XII) 39289 dimethyl 3-[4-(benzyloxy)phenyl]-4-ethylpyrrolo[2,1,5-cd]indolizine-1,2-dicarboxylate C29H25NO5 详情 详情
(XIII) 39290 3-[4-(benzyloxy)phenyl]-4-ethylpyrrolo[2,1,5-cd]indolizine-1,2-dicarboxylic acid C27H21NO5 详情 详情
(XIV) 39291 2-[4-(benzyloxy)phenyl]-1-ethylpyrrolo[2,1,5-cd]indolizine; benzyl 4-(1-ethylpyrrolo[2,1,5-cd]indolizin-2-yl)phenyl ether C25H21NO 详情 详情
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