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【结 构 式】

【分子编号】67669

【品名】4-methoxybenzyl (1-(iodomethyl)cyclopropyl)carbamate

【CA登记号】 

【 分 子 式 】C13H16INO3

【 分 子 量 】361.17945

【元素组成】C 43.23% H 4.47% I 35.14% N 3.88% O 13.29%

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:(XXXVIII)

Treatment of acid (XXXIV) with Pmb-OH in the presence of DPPA and Et3N (through Curtius rearrangement) in refluxing toluene produces carbamate (XXXV), which is reduced at the ethyl ester group to alcohol (XXXVI) by means of NaBH4 in THF/MeOH. Activation of primary alcohol (XXXVI) using MsCl and DIEA in CH2Cl2 at 5 °C gives mesylate (XXXVII), which by treatment with KI in refluxing acetone affords its corresponding iodide (XXXVIII). Condensation of the 7-hydroxyquinoline derivative (IX) with either, mesylate (XXXVII) using K2CO3 in the presence of KI or NaI or with iodide (XXXVIII) using K2CO3 in refluxing acetone yields ether (XXXIX), which is finally deprotected by cleavement of the PMB group by treatment with TFA or p-TsOH in CH2Cl2 or acetonitrile .
Condensation of mesylate (XXXVII) with the 7-hydroxyquinoline derivative (XL) by means of K2CO3 and NaI in refluxing acetone gives ether (XLI), whose ethyl ester group is hydrolyzed with NaOH in EtOH to give acid (XLII). Finally, preactivation of acid (XLII) with CDI, followed by coupling with methylamine hydrochloride (III) in DMF at 80 °C affords amide (XXXIX) .

1 Chen, G.P. (Advenchen Laboratories, LLC). Process for preparing the antitumor agent 6-(7-((1-aminocyclopropyl) methoxy)-6-methoxyquinolin-4-yloxy)-N-methyl-1-naphthamide and its crystalline. WO 2014113616.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(IX) 67633 6-((7-hydroxy-6-methoxyquinolin-4-yl)oxy)-N-methyl-1-naphthamide   C22H18N2O4 详情 详情
(XXXIV) 67665 1-(ethoxycarbonyl)cyclopropanecarboxylic acid   C7H10O4 详情 详情
(XXXV) 67666 ethyl 1-((((4-methoxybenzyl)oxy)carbonyl)amino)cyclopropanecarboxylate   C15H19NO5 详情 详情
(XXXVI) 67667 4-methoxybenzyl (1-(hydroxymethyl)cyclopropyl)carbamate   C13H17NO4 详情 详情
(XXXVII) 67668 (1-((((4-methoxybenzyl)oxy)carbonyl)amino)cyclopropyl)methyl methanesulfonate   C14H19NO6S 详情 详情
(XXXVIII) 67669 4-methoxybenzyl (1-(iodomethyl)cyclopropyl)carbamate   C13H16INO3 详情 详情
(XXXIX) 67671 4-methoxybenzyl (1-(((6-methoxy-4-((5-(methylcarbamoyl)naphthalen-2-yl)oxy)quinolin-7-yl)oxy)methyl)cyclopropyl)carbamate   C35H33N3O7 详情 详情
(XL) 67670 ethyl 6-((7-hydroxy-6-methoxyquinolin-4-yl)oxy)-1-naphthoate C23H19NO5 详情 详情
(XLI) 67672 ethyl 6-((6-methoxy-7-((1-((((4-methoxybenzyl)oxy)carbonyl)amino)cyclopropyl)methoxy)quinolin-4-yl)oxy)-1-naphthoate   C36H34N2O8 详情 详情
(XLII) 67673 6-((6-methoxy-7-((1-((((4-methoxybenzyl)oxy)carbonyl)amino)cyclopropyl)methoxy)quinolin-4-yl)oxy)-1-naphthoic acid   C34H30N2O8 详情 详情
Extended Information