9-(4-bromobutyl)-N-(2,2,2-trifluoroethyl)-9H-fluorene-9-carboxamide -Drug Synthesis Database

【结构式】

【分子编号】47746

【品名】9-(4-bromobutyl)-N-(2,2,2-trifluoroethyl)-9H-fluorene-9-carboxamide

【CA登记号】

【分子式】C₂₀H₁₉BrF₃NO

【分子量】426.2762096

【元素组成】C 56.35% H 4.49% Br 18.74% F 13.37% N 3.29% O 3.75%

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：(IV)

The lithium dianion of 9-fluorenecarboxylic acid (I) was alkylated with 1,4-dibromobutane (II) to afford bromo acid (III). After conversion of (III) to the corresponding acid chloride by treatment with oxalyl chloride, condensation with 2,2,2-trifluoroethylamine furnished the intermediate bromo amide (IV).

参考文献中间体

合成目标

【1】 Sun, C.-Q.; Robl, J.A.; Sulsky, R.; et al.; A novel series of highly potent benzimidazole-based microsomal triglyceride transfer protein inhibitors. J Med Chem 2001, 44, 6, 851.
【3】 Sulsky, R.B.; Poss, M.A.; Slusarchyk, W.A.; Dickson, J.K.; Biller, S.A.; Tino, J.A.; Magnin, D.R.; Lawrence, R.M.; Robl, J.A.; Conformationally restricted aromatic inhibitors of microsomal triglyceride transfer protein and method. US 5760246 .
【2】 Biller, S.A.; Dickson, J.K.; Lawrence, R.M.; Magnin, D.R.; Poss, M.A.; Robl, J.A.; Slusarchyk, W.A.; Sulsky, R.B.; Tino, J.A. (Bristol-Myers Squibb Co.); Conformationally restricted aromatic inhibitors of microsomal triglyceride transfer protein and method. EP 0904262; JP 2000502355; WO 9726240 .

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)	47744	9H-fluorene-9-carboxylic acid; 9-Fluorenecarboxylic acid; Diphenyleneacetic acid; Fluorene-9-carboxylic acid	1989-33-9	C₁₄H₁₀O₂	详情	详情
(II)	11883	1,4-Dibromobutane; 1,4-Butylene bromide	110-52-1	C₄H₈Br₂	详情	详情
(III)	47745	9-(4-bromobutyl)-9H-fluorene-9-carboxylic acid		C₁₈H₁₇BrO₂	详情	详情
(IV)	47746	9-(4-bromobutyl)-N-(2,2,2-trifluoroethyl)-9H-fluorene-9-carboxamide		C₂₀H₁₉BrF₃NO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

The requisite nitrodiamine (VIII) was prepared via conversion of 4-methyl-1,2-phenylenediamine (V) to the selenocycle (VI) upon treatment with SeO2 and HCl, followed by nitration to afford regioselectively the nitro derivative (VII). Conversion to the diamine (VIII) was effected by treatment of (VII) with HI. Subsequent reaction of (VIII) with 2,4-pentanedione (IX) in the presence of HCl gave rise to the benzimidazole (X). Alkylation of (X) with bromide (IV) using K2CO3 in DMF provided adduct (XI) as the major regioisomer. Catalytic hydrogenation of the nitro group of (XI) then gave amine (XII). Finally, coupling of amine (XII) with 4'-(trifluoromethyl)biphenyl-2-carboxylic acid (XIII) was achieved via EDC activation or by previous conversion of (XIII) to the corresponding acid chloride with oxalyl chloride.

参考文献中间体

合成目标

【1】 Sun, C.-Q.; Robl, J.A.; Sulsky, R.; et al.; A novel series of highly potent benzimidazole-based microsomal triglyceride transfer protein inhibitors. J Med Chem 2001, 44, 6, 851.
【3】 Sulsky, R.B.; Poss, M.A.; Slusarchyk, W.A.; Dickson, J.K.; Biller, S.A.; Tino, J.A.; Magnin, D.R.; Lawrence, R.M.; Robl, J.A.; Conformationally restricted aromatic inhibitors of microsomal triglyceride transfer protein and method. US 5760246 .
【2】 Biller, S.A.; Dickson, J.K.; Lawrence, R.M.; Magnin, D.R.; Poss, M.A.; Robl, J.A.; Slusarchyk, W.A.; Sulsky, R.B.; Tino, J.A. (Bristol-Myers Squibb Co.); Conformationally restricted aromatic inhibitors of microsomal triglyceride transfer protein and method. EP 0904262; JP 2000502355; WO 9726240 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IV)	47746	9-(4-bromobutyl)-N-(2,2,2-trifluoroethyl)-9H-fluorene-9-carboxamide		C₂₀H₁₉BrF₃NO	详情	详情
(V)	47747	4-methyl-1,2-benzenediamine; 2-amino-4-methylphenylamine; 3,4-Diaminotoluene; 3,4-Toluenediamine; 4-methyl-1,2-phenylenediamine; 4-Methyl-O-Phenylenediamine; asym-o-Tolylenediamine; o-Toluylenediamine; ortho-toluenediamine; Tolylene-3,4-diamine	496-72-0	C₇H₁₀N₂	详情	详情
(VI)	47748	5-methyl-2,1,3-benzoselenadiazole		C₇H₆N₂Se	详情	详情
(VII)	47749	5-methyl-4-nitro-2,1,3-benzoselenadiazole		C₇H₅N₃O₂Se	详情	详情
(VIII)	47750	2-amino-4-methyl-3-nitrophenylamine; 4-methyl-3-nitro-1,2-benzenediamine		C₇H₉N₃O₂	详情	详情
(IX)	11620	2,4-Pentanedione;acetylacetone	123-54-6	C₅H₈O₂	详情	详情
(X)	47751	2,5-dimethyl-4-nitro-1H-benzimidazole		C₉H₉N₃O₂	详情	详情
(XI)	47752	9-[4-(2,5-dimethyl-4-nitro-1H-benzimidazol-1-yl)butyl]-N-(2,2,2-trifluoroethyl)-9H-fluorene-9-carboxamide		C₂₉H₂₇F₃N₄O₃	详情	详情
(XII)	47753	9-[4-(4-amino-2,5-dimethyl-1H-benzimidazol-1-yl)butyl]-N-(2,2,2-trifluoroethyl)-9H-fluorene-9-carboxamide		C₂₉H₂₉F₃N₄O	详情	详情
(XIII)	41132	4'-(trifluoromethyl)[1,1'-biphenyl]-2-carboxylic acid		C₁₄H₉F₃O₂	详情	详情

Extended Information