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【结 构 式】

【分子编号】33107

【品名】[2,7-dichloro-6-methyl-4-[(4-methyl-1-piperidinyl)methyl]-3-quinolinyl]methanol

【CA登记号】

【 分 子 式 】C18H22Cl2N2O

【 分 子 量 】353.29096

【元素组成】C 61.2% H 6.28% Cl 20.07% N 7.93% O 4.53%

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:(XIV)

Acylation of 3-chloro-4-methylaniline (VII) with chloroacetonitrile in the presence of BCl3 and Et2AlCl produced the chloroacetophenone (VIII). Subsequent condensation of (VIII) with ethylmalonyl chloride gave amide (IX), which was cyclized to the quinolinone (X) upon treatment with ethanolic NaOEt. Reaction of the quinolinone (X) with POCl3 afforded chloroquinoline (XI). The ester group of (XI) was then reduced to alcohol (XII) by means of diisobutylaluminum hydride. Condensation of (XII) with 4-methylpiperidine (XIII) gave adduct (IV), which was further coupled with pyridinone (VI) under Mitsunobu conditions to yield (Xv). Finally, intramolecular Heck reaction in the presence of palladium diacetate and triphenylphosphine provided the desired pentacyclic compound, which was isolated as the hydrochloride salt.

1 Coulomb, H.; Huchet, M.; Harnett, J.; Rolland, A.; Lanco, C.; Lavergne, O.; Demarquay, D.; Lesueur-Ginot, L.; Bigg, D.C.H.; BN 80927: A novel homocamptothecin with inhibitory activities on both topoisomerase I and topoisomerase II. Bioorg Med Chem Lett 1999, 9, 17, 2599.
2 Cazaux, J.-B.; Manginot, E.; Lavergne, O.; Le Breton, C.; Bigg, D. (SCRAS (Societé de Conseils de Recherches et d'Applications Scientifiques)); Optically pure camptothecin analogues, optically pure synthesis intermediate and method for preparing same. EP 1007527; FR 2768431; WO 9911646 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(VI) 33100 (5R)-5-ethyl-5-hydroxy-1,4,5,8-tetrahydrooxepino[3,4-c]pyridine-3,9-dione C11H13NO4 详情 详情
(VII) 26794 3-Chloro-4-methylaniline; 4-Amino-2-chlorotoluene 95-74-9 C7H8ClN 详情 详情
(VIII) 33102 1-(2-amino-4-chloro-5-methylphenyl)-2-chloro-1-ethanone C9H9Cl2NO 详情 详情
(IX) 33013 O-[tert-butyl(diphenyl)silyl]hydroxylamine; (aminooxy)(tert-butyl)diphenylsilane C16H21NOSi 详情 详情
(X) 33104 ethyl 7-chloro-4-(chloromethyl)-6-methyl-2-oxo-1,2-dihydro-3-quinolinecarboxylate C14H13Cl2NO3 详情 详情
(XI) 33105 ethyl 2,7-dichloro-4-(chloromethyl)-6-methyl-3-quinolinecarboxylate C14H12Cl3NO2 详情 详情
(XII) 33106 [2,7-dichloro-4-(chloromethyl)-6-methyl-3-quinolinyl]methanol C12H10Cl3NO 详情 详情
(XIII) 10192 4-Methylpiperidine; gamma-Pipecoline 626-58-4 C6H13N 详情 详情
(XIV) 33107 [2,7-dichloro-6-methyl-4-[(4-methyl-1-piperidinyl)methyl]-3-quinolinyl]methanol C18H22Cl2N2O 详情 详情
(XV) 33101 (5R)-8-[(2-chloro-6,7-difluoro-3-quinolinyl)methyl]-5-ethyl-5-hydroxy-1,4,5,8-tetrahydrooxepino[3,4-c]pyridine-3,9-dione C21H17ClF2N2O4 详情 详情
Extended Information