ethyl 3-methyl-4-{3-[(3-pyridinylmethyl)amino]propoxy}-1-benzofuran-2-carboxylate -Drug Synthesis Database

【结构式】

【分子编号】52875

【品名】ethyl 3-methyl-4-{3-[(3-pyridinylmethyl)amino]propoxy}-1-benzofuran-2-carboxylate

【CA登记号】

【分子式】C₂₁H₂₄N₂O₄

【分子量】368.43264

【元素组成】C 68.46% H 6.57% N 7.6% O 17.37%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(V)

Alkylation of ethyl 4-hydroxy-3-methylbenzofuran-2-carboxylate (I) with 1,3-dibromopropane (II) in the presence of K2CO3 produced the bromopropyl ether (III). Subsequent displacement of the remaining bromine of (III) with 3-picolylamine (IV) furnished the secondary amine (V). The ester group of (V) was then reduced to alcohol (VI) with LiAlH4. Finally, Mitsunobu coupling of alcohol (VI) with 2,4-difluorophenol (VII) in the presence of 1,1'-(azodicarbonyl)dipiperidine and tributylphosphine gave rise to the target difluorophenyl ether.

参考文献中间体

合成目标

【1】 Ebiike, H.; Masubuchi, M.; Liu, P.; Kawasaki, K.,-I.; Morikami, K.; Sogabe, S.; Hayase, M.; Fujii, T.; Sakata, K.; Shindoh, H.; Shiratori, Y.; Aoki, Y.; Ohtsuka, T.; Shimma, N.; Design and synthesis of novel benzofurans as a new class of antifungal agents targeting fungal N-myristoyltransferase. Part 2. Bioorg Med Chem Lett 2002, 12, 4, 607.
【2】 Fujii, T.; Tsujii, S.; Liu, P.; Ohtsuka, T.; Ebiike, H.; Masubuchi, M.; Aoki, Y.; Kawasaki, K. (F. Hoffmann-La Roche AG); Novel bicyclic cpds.. US 6376491; WO 0037464 .

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)	52126	ethyl 4-hydroxy-3-methyl-1-benzofuran-2-carboxylate		C₁₂H₁₂O₄	详情	详情
(II)	12581	1,3-Dibromopropane	109-64-8	C₃H₆Br₂	详情	详情
(III)	52127	ethyl 4-(3-bromopropoxy)-3-methyl-1-benzofuran-2-carboxylate		C₁₅H₁₇BrO₄	详情	详情
(IV)	18731	3-pyridinylmethanamine; 3-pyridinylmethylamine	3731-52-0	C₆H₈N₂	详情	详情
(V)	52875	ethyl 3-methyl-4-{3-[(3-pyridinylmethyl)amino]propoxy}-1-benzofuran-2-carboxylate		C₂₁H₂₄N₂O₄	详情	详情
(VI)	52876	(3-methyl-4-{3-[(3-pyridinylmethyl)amino]propoxy}-1-benzofuran-2-yl)methanol		C₁₉H₂₂N₂O₃	详情	详情
(VII)	21486	2,4-difluorophenol	367-27-1	C₆H₄F₂O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

Condensation of ethyl 4-hydroxy-3-methylbenzofuran-2-carboxylate (I) with 1,3-dibromopropane (II) affords the benzofuran bromopropyl ether (III). Subsequent displacement of bromide (III) with 3-picolylamine (IV) yields amine (V). The ester group of (V) is then reduced with LiAlH4 to furnish alcohol (VI). Finally, Mitsunobu coupling between alcohol (VI) and 2,3,4-trifluorophenol (VII) in the presence of 1,1'-(azodicarbonyl)dipiperidine (ADDP) and tributylphosphine provides the title compound

参考文献中间体

合成目标

【1】 Ebiike, H.; Masubuchi, M.; Kawasaki, K.-I.; et al.; Design and synthesis of novel N-myristoyltransferase inhibitors as antifungal agents. 224th ACS Natl Meet (Aug 18 2002, Boston) 2002, Abst MEDI 56.
【2】 Ebiike, H.; Masubuchi, M.; Liu, P.; Kawasaki, K.,-I.; Morikami, K.; Sogabe, S.; Hayase, M.; Fujii, T.; Sakata, K.; Shindoh, H.; Shiratori, Y.; Aoki, Y.; Ohtsuka, T.; Shimma, N.; Design and synthesis of novel benzofurans as a new class of antifungal agents targeting fungal N-myristoyltransferase. Part 2. Bioorg Med Chem Lett 2002, 12, 4, 607.
【3】 Fujii, T.; Tsujii, S.; Liu, P.; Ohtsuka, T.; Ebiike, H.; Masubuchi, M.; Aoki, Y.; Kawasaki, K. (F. Hoffmann-La Roche AG); Novel bicyclic cpds.. US 6376491; WO 0037464 .

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)	52126	ethyl 4-hydroxy-3-methyl-1-benzofuran-2-carboxylate		C₁₂H₁₂O₄	详情	详情
(II)	12581	1,3-Dibromopropane	109-64-8	C₃H₆Br₂	详情	详情
(III)	52127	ethyl 4-(3-bromopropoxy)-3-methyl-1-benzofuran-2-carboxylate		C₁₅H₁₇BrO₄	详情	详情
(IV)	18731	3-pyridinylmethanamine; 3-pyridinylmethylamine	3731-52-0	C₆H₈N₂	详情	详情
(V)	52875	ethyl 3-methyl-4-{3-[(3-pyridinylmethyl)amino]propoxy}-1-benzofuran-2-carboxylate		C₂₁H₂₄N₂O₄	详情	详情
(VI)	53876	N-(5,6-dimethoxy-2,3-dihydro-1H-inden-2-yl)-N,N-dipropylamine; 5,6-dimethoxy-N,N-dipropyl-2-indanamine	n/a	C₁₇H₂₇NO₂	详情	详情
(VII)	60408	2,3,4-trifluorophenol		C₆H₃F₃O	详情	详情

Extended Information