9H-fluorene-9-carboxylic acid; 9-Fluorenecarboxylic acid; Diphenyleneacetic acid; Fluorene-9-carboxylic acid -Drug Synthesis Database

【结构式】

【分子编号】47744

【品名】9H-fluorene-9-carboxylic acid; 9-Fluorenecarboxylic acid; Diphenyleneacetic acid; Fluorene-9-carboxylic acid

【CA登记号】1989-33-9

【分子式】C₁₄H₁₀O₂

【分子量】210.2322

【元素组成】C 79.98% H 4.79% O 15.22%

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：(I)

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：(I)

Alkylation of the dilithio derivative of fluorene-9-carboxylic acid (I) with diethyl 4-bromobutylphosphonate (II) affords adduct (III). After conversion of acid (III) to the corresponding acid chloride (IV), condensation with 2,2,2-trifluoroethylamine (V) affords amide (VI). The phosphonate ethyl ester (VI) is cleaved by means of bromotrimethylsilane yielding phosphonic acid (VII), which is further activated as the phosphonic acid chloride (VIII) by using oxalyl chloride in the presence of DMF. Finally, condensation of acid chloride (VIII) with (6-methylpyridin-2-yl)methanol (IX) leads to the target bis-pyridinylmethyl ester.

参考文献中间体

合成目标

【1】 Magnin, D.R.; Biller, S.A.; Wetterau, J.; Robl, J.A.; Dickson, J.K. Jr.; Prakash, T.; Harrity, T.W.; Lawrence, R.M.; Sun, C.-Q.; Wang, T.; Logan, J.; Fryszman, O.; Connolly, F.; Jolibois, K.; Kunselman, L.; Microsomal triglyceride transfer protein inhibitors: Discovery and synthesis of alkyl phosphonates as potent MTP inhibitors and cholesterol lowering agents. Bioorg Med Chem Lett 2003, 13, 7, 1337.

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)	64229	diethyl 4-bromobutylphosphonate		C₈H₁₈BrO₃P	详情	详情
(III)	64230	9-[4-(diethoxyphosphoryl)butyl]-9H-fluorene-9-carboxylic acid		C₂₂H₂₇O₅P	详情	详情
(IV)	64231	diethyl 4-[9-(chlorocarbonyl)-9H-fluoren-9-yl]butylphosphonate		C₂₂H₂₆ClO₄P	详情	详情
(V)	42542	2,2,2-trifluoroethylamine; 2,2,2-trifluoro-1-ethanamine	753-90-2	C₂H₄F₃N	详情	详情
(VI)	64232	diethyl 4-(9-{[(2,2,2-trifluoroethyl)amino]carbonyl}-9H-fluoren-9-yl)butylphosphonate		C₂₄H₂₉F₃NO₄P	详情	详情
(VII)	64233	4-(9-{[(2,2,2-trifluoroethyl)amino]carbonyl}-9H-fluoren-9-yl)butylphosphonic acid		C₂₀H₂₁F₃NO₄P	详情	详情
(VIII)	64234	4-(9-{[(2,2,2-trifluoroethyl)amino]carbonyl}-9H-fluoren-9-yl)butylphosphonic dichloride		C₂₀H₁₉Cl₂F₃NO₂P	详情	详情
(IX)	64235	(6-methyl-2-pyridinyl)methanol		C₇H₉NO	详情	详情

Extended Information