【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% |
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 |