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【结 构 式】

【分子编号】49879

【品名】5-(4-[3-chloro-4-[(3-fluorobenzyl)oxy]anilino]-6-quinazolinyl)-2-furaldehyde

【CA登记号】

【 分 子 式 】C26H17ClFN3O3

【 分 子 量 】473.8905032

【元素组成】C 65.9% H 3.62% Cl 7.48% F 4.01% N 8.87% O 10.13%

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:(IX)

Williamson's ether synthesis between 2-chloro-4-nitrophenol (I) and 3-fluorobenzyl bromide (II) afforded ether (III). The nitro group of (III) was then reduced to the aniline (IV) by means of catalytic hydrogenation over Pt/C. Condensation of aniline (IV) with 4-chloro-6-iodoquinazoline (V) furnished the diaryl amine (VI). Subsequent Stille coupling between iodide (VI) and 5-dioxolanyl-2-(tributylstannyl)furan (VII) gave rise to adduct (VIII), which was further subjected to acid hydrolysis of the cyclic ketal to yield aldehyde (IX). Finally, reductive amination of (IX) with 2-(methanesulfonyl)ethylamine (X) in the presence of sodium triacetoxyborohydride provided the title compound.

1 Guntrip, S.B.; Lackey, K.E.; Cockerill, G.S.; Carter, M.C.; Smith, K.J. (Glaxo Group Ltd.); Bicyclic heteroaromatic cpds. as protein tyrosine kinase inhibitors. EP 1047694; WO 9935146 .
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) 49872 1-Chloro-2-Hydroxy-5-Nitrobenzene; 2-Chloro-4-nitrophenol; 4-Nitro-2-chlorophenol; p-Nitro-o-chlorophenol 619-08-9 C6H4ClNO3 详情 详情
(II) 17221 3-Fluorobenzyl bromide; 1-(bromomethyl)-3-fluorobenzene 456-41-7 C7H6BrF 详情 详情
(III) 49873 2-chloro-1-[(3-fluorobenzyl)oxy]-4-nitrobenzene; 2-chloro-4-nitrophenyl 3-fluorobenzyl ether C13H9ClFNO3 详情 详情
(IV) 49874 3-chloro-4-[(3-fluorobenzyl)oxy]phenylamine; 3-chloro-4-[(3-fluorobenzyl)oxy]aniline C13H11ClFNO 详情 详情
(V) 49875 4-chloro-6-iodoquinazoline 98556-31-1 C8H4ClIN2 详情 详情
(VI) 49876 N-[3-chloro-4-[(3-fluorobenzyl)oxy]phenyl]-N-(6-iodo-4-quinazolinyl)amine; N-[3-chloro-4-[(3-fluorobenzyl)oxy]phenyl]-6-iodo-4-quinazolinamine C21H14ClFIN3O 详情 详情
(VII) 49877 tributyl[5-(1,3-dioxolan-2-yl)-2-furyl]stannane C19H34O3Sn 详情 详情
(VIII) 49878 N-[3-chloro-4-[(3-fluorobenzyl)oxy]phenyl]-6-[5-(1,3-dioxolan-2-yl)-2-furyl]-4-quinazolinamine; N-[3-chloro-4-[(3-fluorobenzyl)oxy]phenyl]-N-[6-[5-(1,3-dioxolan-2-yl)-2-furyl]-4-quinazolinyl]amine C28H21ClFN3O4 详情 详情
(IX) 49879 5-(4-[3-chloro-4-[(3-fluorobenzyl)oxy]anilino]-6-quinazolinyl)-2-furaldehyde C26H17ClFN3O3 详情 详情
(X) 49880 2-(methylsulfonyl)-1-ethanamine; 2-(methylsulfonyl)ethylamine C3H9NO2S 详情 详情

合成路线2

该中间体在本合成路线中的序号:(XIII)

 

1 Petrov KG, Zhang YM, Carter M, et al. 2006. Optimization and SAR for dual ErbB-1/ErbB-2 tyrosine kinase inhibition in the 6-furanylquinazoline series. Bioorganic & Medicinal Chemistry Letters, 16, 4686~4691.
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) 11240 2-(Methylsulfanyl)ethylamine; 2-(Methylthio)ethylamine; 2-(Methylsulfanyl)-1-ethanamine 18542-42-2 C3H9NS 详情 详情
(II) 67211 benzyl (2-(methylthio)ethyl)carbamate   C11H15NO2S 详情 详情
(III) 67212 benzyl (2-(methylsulfonyl)ethyl)carbamate   C11H15NO4S 详情 详情
(IV) 49880 2-(methylsulfonyl)-1-ethanamine; 2-(methylsulfonyl)ethylamine C3H9NO2S 详情 详情
(VI) 49872 1-Chloro-2-Hydroxy-5-Nitrobenzene; 2-Chloro-4-nitrophenol; 4-Nitro-2-chlorophenol; p-Nitro-o-chlorophenol 619-08-9 C6H4ClNO3 详情 详情
(VII) 17221 3-Fluorobenzyl bromide; 1-(bromomethyl)-3-fluorobenzene 456-41-7 C7H6BrF 详情 详情
(VIII) 49873 2-chloro-1-[(3-fluorobenzyl)oxy]-4-nitrobenzene; 2-chloro-4-nitrophenyl 3-fluorobenzyl ether C13H9ClFNO3 详情 详情
(IX) 49874 3-chloro-4-[(3-fluorobenzyl)oxy]phenylamine; 3-chloro-4-[(3-fluorobenzyl)oxy]aniline C13H11ClFNO 详情 详情
(X) 49875 4-chloro-6-iodoquinazoline 98556-31-1 C8H4ClIN2 详情 详情
(XI) 49876 N-[3-chloro-4-[(3-fluorobenzyl)oxy]phenyl]-N-(6-iodo-4-quinazolinyl)amine; N-[3-chloro-4-[(3-fluorobenzyl)oxy]phenyl]-6-iodo-4-quinazolinamine C21H14ClFIN3O 详情 详情
(XII) 67214 (5-formylfuran-2-yl)boronic acid 27329-70-0 C5H5BO4 详情 详情
(XIII) 49879 5-(4-[3-chloro-4-[(3-fluorobenzyl)oxy]anilino]-6-quinazolinyl)-2-furaldehyde C26H17ClFN3O3 详情 详情
Extended Information