1-(4-fluorophenethyl)-4-piperidinecarboxamide -Drug Synthesis Database

【结构式】

【分子编号】17395

【品名】1-(4-fluorophenethyl)-4-piperidinecarboxamide

【CA登记号】

【分子式】C₁₄H₁₉FN₂O

【分子量】250.3161432

【元素组成】C 67.18% H 7.65% F 7.59% N 11.19% O 6.39%

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：(III)

MDL-100907 can be obtained by several different ways: 1) The condensation of piperidine-4-carboxamide (I) with 2-(4-fluorophenyl)ethyl bromide (II) by means of K2CO3 in hot DMF gives 1-[2-(4-fluorophenyl)ethyl]piperidine-4-carboxamide (III), which by reaction with refluxing POCl3 is converted into the nitrile (IV). The reduction of (IV) with diisobutyl aluminum hydride (DIBAL) in THF affords the aldehyde (V), which by condensation with 1,2-dimethoxybenzene (veratrole) (VI) by means of BuLi in THF affords racemic MDL-100907 (VII). The esterification of (VII) with (S)-2-methoxy-2-phenylacetic acid (VIII) by means of dicyclohexylcarbodiimide (DCC) and dimethyl-aminopyridine (DMAP) in refluxing CHCl3 affords a mixture of diastereomers that is submitted to column chromatography over silica gel to afford the pure diastereomer (IX). Finally, (IX) is saponified with K2CO3 in methanol/ water

参考文献中间体

合成目标

【1】 Castaner, J.; Sorbera, L.A.; Silvestre, J.S.; MDL-100907. Drugs Fut 1998, 23, 9, 955.
【2】 Carr, A.A.; Kane, J.M.; Hay, D.A. (Merrell Pharmaceuticals, Inc.); (+)-*-(2,3-Dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol. EP 0531410; JP 1993507482; US 5134149; WO 9118602 .

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)	11762	4-Piperidinecarboxamide; Isonipecotamide	39546-32-2	C₆H₁₂N₂O	详情	详情
(II)	17394	1-(2-bromoethyl)-4-fluorobenzene		C₈H₈BrF	详情	详情
(III)	17395	1-(4-fluorophenethyl)-4-piperidinecarboxamide		C₁₄H₁₉FN₂O	详情	详情
(IV)	17396	1-(4-fluorophenethyl)-4-piperidinecarbonitrile		C₁₄H₁₇FN₂	详情	详情
(V)	17397	1-(4-fluorophenethyl)-4-piperidinecarbaldehyde		C₁₄H₁₈FNO	详情	详情
(VI)	17398	2-methoxyphenyl methyl ether; Veratrole; 1,2-dimethoxybenzene	91-16-7	C₈H₁₀O₂	详情	详情
(VII)	17399	(2,3-dimethoxyphenyl)[1-(4-fluorophenethyl)-4-piperidinyl]methanol		C₂₂H₂₈FNO₃	详情	详情
(VIII)	17400	(2S)-2-methoxy-2-phenylethanoic acid		C₉H₁₀O₃	详情	详情
(IX)	17401	(R)-(2,3-dimethoxyphenyl)[1-(4-fluorophenethyl)-4-piperidinyl]methyl (2S)-2-methoxy-2-phenylethanoate		C₃₁H₃₆FNO₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

Irisquinone was originally isolated from some Iris species. The total synthesis of this compound has been reported by several procedures. 10-cis-Heptadecenoic acid (I) was converted to the Weinreb amide (II) via the corresponding acid chloride. Regiospecific ortho-lithiation of veratrole (III), followed by acylation with the N-methoxy amide (II), afforded ketone (IV). Selective mono-demethylation of (IV) with boron trichloride yielded phenol (V). Clemmensen reduction of the keto group of (V) employing zinc amalgam furnished 2-(cis-10-heptadecenyl)-6-methoxyphenol (VI). This was finally oxidized to the target quinone by means of oxygen gas in the presence of salcomine.

参考文献中间体

合成目标

【1】 Haugwitz, R.D.; Risbood, P.A.; Parsons, J.L.; Myers, D.R.; Michalak, R.S.; Narayanan, V.L.; The synthesis of irisquinone. Tetrahedron Lett 1989, 30, 36, 4783.

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)	56670	cis-10-Heptadecenoic acid	29743-97-3	C₁₇H₃₂O₂	详情	详情
(II)	56671	(Z)-N-methoxy-N-methyl-10-heptadecenamide		C₁₉H₃₇NO₂	详情	详情
(III)	17395	1-(4-fluorophenethyl)-4-piperidinecarboxamide		C₁₄H₁₉FN₂O	详情	详情
(IV)	56672	(Z)-1-(2,3-dimethoxyphenyl)-10-heptadecen-1-one		C₂₅H₄₀O₃	详情	详情
(V)	56673	(Z)-1-(2-hydroxy-3-methoxyphenyl)-10-heptadecen-1-one		C₂₄H₃₈O₃	详情	详情
(VI)	56674	2-[(Z)-10-heptadecenyl]-6-methoxyphenol		C₂₄H₄₀O₂	详情	详情

Extended Information