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【结 构 式】

【分子编号】67651

【品名】tert-butyl (1-((4-acetyl-2-methoxyphenoxy)methyl)cyclopropyl)carbamate

【CA登记号】 

【 分 子 式 】C18H25NO5

【 分 子 量 】335.40024

【元素组成】C 64.46% H 7.51% N 4.18% O 23.85%

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:(XXVIIc)

Mitsunobu reaction of apocynin (XIII) with the cyclopropylmethanol derivatives (XIa-c) in the presence of DEAD, PPh3 and DIEA in THF affords the aryl ethers (XXVIIa-c), which by nitration with HNO3 in Ac2O yields the 6-nitrophenyl derivatives (XXVIIIa-c). Condensation of ketones (XXVIIIa-c) with dimethylformamide dimethylacetal (XXIX) in DMF at 100 °C furnishes keto-enamines (XXXa-c), which upon Leimgruber-Batcho reaction using Fe in AcOH at 80 °C produces quinoline derivatives (XXXIa-c). Chlorination of 4-hydroxyquinolines (XXXIa-c) with POCl3 at 85 °C gives their corresponding chlorides (XXXIIa-c). These compounds are alternatively obtained by Mitsunobu condensation of 4-chloro-7-hydroxy-6-methoxyquinoline (XXXIII) with alcohols (Xia-c) using DEAD and PPh3 in CH2Cl2 at 0 °C. Condensation of chlorides (XXXIIa-c) with 6-hydroxy-N-methyl-1-naphthamide (V) by means of DMAP in 2,6-lutidine at 140 °C yields ethers (XIIa-c), whose N-carbamates are cleaved by means of HBr in AcOH .

1 Spinelli, S., Livi, V. (EOS SpA). A process for the preparation of 6-(7-((1-aminocyclopropyl)methoxy)-6-methoxyquinolin-4-yloxy)-N-methyl-1-naphthamide and synthetic intermediates thereof. US 9012645; US 2014114075; CN 102356063; US 8642767; US 2012010415; EP 2408739; US 2015191429; WO 2010105761; EP 2641897; JP 2012520332.
2 Spinelli, S., Livi, V. (EOS SpA). Preparation method of compound and a synthesis intermediate. CN 104193676.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XIa) 67635 benzyl (1-(hydroxymethyl)cyclopropyl)carbamate C12H15NO3 详情 详情
(XIb) 67647 ethyl (1-(hydroxymethyl)cyclopropyl)carbamate C7H13NO3 详情 详情
(XIc) 67648 tert-butyl (1-(hydroxymethyl)cyclopropyl)carbamate 107017-73-2 C9H17NO3 详情 详情
(XXVIIa) 67649 benzyl (1-((4-acetyl-2-methoxyphenoxy)methyl)cyclopropyl)carbamate   C21H23NO5 详情 详情
(XXVIIb) 67650 ethyl (1-((4-acetyl-2-methoxyphenoxy)methyl)cyclopropyl)carbamate   C16H21NO5 详情 详情
(XXVIIc) 67651 tert-butyl (1-((4-acetyl-2-methoxyphenoxy)methyl)cyclopropyl)carbamate   C18H25NO5 详情 详情
(XXVIIIa) 67653 benzyl (1-((4-acetyl-2-methoxy-5-nitrophenoxy)methyl)cyclopropyl)carbamate C21H22N2O7 详情 详情
(XXVIIIb) 67654 ethyl (1-((4-acetyl-2-methoxy-5-nitrophenoxy)methyl)cyclopropyl)carbamate   C16H20N2O7 详情 详情
(XXVIIIc) 67652 tert-butyl (1-((4-acetyl-2-methoxy-5-nitrophenoxy)methyl)cyclopropyl)carbamate   C18H24N2O7 详情 详情
(XXXa) 67656 (E)-benzyl (1-((4-(3-(dimethylamino)acryloyl)-2-methoxy-5-nitrophenoxy)methyl)cyclopropyl)carbamate   C24H27N3O7 详情 详情
(XXXb) 67655 (E)-ethyl (1-((4-(3-(dimethylamino)acryloyl)-2-methoxy-5-nitrophenoxy)methyl)cyclopropyl)carbamate   C19H25N3O7 详情 详情
(XXXc) 67657 (E)-tert-butyl (1-((4-(3-(dimethylamino)acryloyl)-2-methoxy-5-nitrophenoxy)methyl)cyclopropyl)carbamate   C21H29N3O7 详情 详情
(XXXIa) 67658 benzyl (1-(((4-hydroxy-6-methoxyquinolin-7-yl)oxy)methyl)cyclopropyl)carbamate   C22H22N2O5 详情 详情
(XXXIb) 67659 ethyl (1-(((4-hydroxy-6-methoxyquinolin-7-yl)oxy)methyl)cyclopropyl)carbamate C17H20N2O5 详情 详情
(XXXIc) 67660 tert-butyl (1-(((4-hydroxy-6-methoxyquinolin-7-yl)oxy)methyl)cyclopropyl)carbamate   C19H24N2O5 详情 详情
(XXXIIa) 67663 benzyl (1-(((4-chloro-6-methoxyquinolin-7-yl)oxy)methyl)cyclopropyl)carbamate   C22H21ClN2O4 详情 详情
(XXXIIb) 67662 ethyl (1-(((4-chloro-6-methoxyquinolin-7-yl)oxy)methyl)cyclopropyl)carbamate   C17H19ClN2O4 详情 详情
(XXXIIc) 67661 tert-butyl (1-(((4-chloro-6-methoxyquinolin-7-yl)oxy)methyl)cyclopropyl)carbamate   C19H23ClN2O4 详情 详情
(V) 67629 6-hydroxy-N-methyl-1-naphthamide   C12H11NO2 详情 详情
(XIII) 22604 1-(4-hydroxy-3-methoxyphenyl)-1-ethanone;Acetovanillone;4’-hydroxy-3’-methoxyacetophenone;1-(4-hydroxy-3-methoxyphenyl)ethanone 498-02-2 C9H10O3 详情 详情
(XXIX) 11984 N-(Dimethoxymethyl)-N,N-dimethylamine;dimethylformamide dimethylacetal;1,1-dimethoxy-N,N-dimethylmethanamine; Dimethoxy-N,N-dimethylmethanamine; N,N-Dimethylformamide dimethyl acetal 4637-24-5 C5H13NO2 详情 详情
(XXXIII) 67664 4-chloro-6-methoxyquinolin-7-ol   C10H8ClNO2 详情 详情
Extended Information