2-[3-(Diisopropylamino)-1-phenylpropyl]-4-methylphenol -Drug Synthesis Database

【结构式】

【分子编号】13567

【品名】2-[3-(Diisopropylamino)-1-phenylpropyl]-4-methylphenol

【CA登记号】

【分子式】C₂₂H₃₁NO

【分子量】325.49428

【元素组成】C 81.18% H 9.6% N 4.3% O 4.92%

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：(VII)

The reaction of 6-methyl-4-phenyl-3,4-dihydro-2H-1-benzopyran-2-one (I) with methyl iodide and K2CO3 in refluxing acetone/methanol or dimethyl sulfate and NaOH gives 3-(2-methoxy-5-phenylphenyl)-3-phenylpropionic acid methyl ester (II), which is reduced with LiAlH4 in ether or NaBH4 and AlCl3 to the corresponding propanol (III). The reduction of (III) with tosyl chloride and pyridine yields the expected tosylate (IV), which by condensation with diisopropylamine (V) in hot acetonitrile is converted into the tertiary amine (VI). Finally, this compound is treated with BBr3 in dichloromethane or HBr to afford the expected amine (VII) as a racemic mixture, which is resolved with L-(+)-tartaric acid.

参考文献中间体

合成目标

【1】 Graul, A.; Martel, A.M.; Castaner, J.; Tolterodine. Drugs Fut 1997, 22, 7, 733.
【2】 Jonsson, N.A.; Sparf, B.A.; Mikiver, L.; Moses, P.; Nilvebrant, L.; Glas, G. (Pharmacia Corp.); New amines, their use and preparation. EP 0325571; JP 1991503163; US 5382600; WO 8906644 .
【3】 Kumar, Y.; Prasad, M.; Neela, P.K.; Misra, S. (Ranbaxy Laboratories Ltd.); Process for the preparation of tolterodine. WO 0314060 .

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)	13561	6-Methyl-4-phenyl-2-chromanone		C₁₆H₁₄O₂	详情	详情
(II)	13562	methyl 3-(2-methoxy-5-methylphenyl)-3-phenylpropanoate		C₁₈H₂₀O₃	详情	详情
(III)	13563	3-(2-Methoxy-5-methylphenyl)-3-phenyl-1-propanol		C₁₇H₂₀O₂	详情	详情
(IV)	13564	3-(2-methoxy-5-methylphenyl)-3-phenylpropyl 4-methylbenzenesulfonate		C₂₄H₂₆O₄S	详情	详情
(V)	13565	N-Isopropyl-2-propanamine; Bis(isopropyl)amine; N,N-Diisopropylamine	108-18-9	C₆H₁₅N	详情	详情
(VI)	13566	N,N-Diisopropyl-N-[3-(2-methoxy-5-methylphenyl)-3-phenylpropyl]amine; N,N-Diisopropyl-3-(2-methoxy-5-methylphenyl)-3-phenyl-1-propanamine		C₂₃H₃₃NO	详情	详情
(VII)	13567	2-[3-(Diisopropylamino)-1-phenylpropyl]-4-methylphenol		C₂₂H₃₁NO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

A new process for the preparation of tolterodine has been described: The cyclization of trans-cinnamic acid (I) with p-cresol (II) by means of hot sulfuric acid gives 6-methyl-4-phenyl-3,4-dihydro-2H-1-benzopyran-2-one (III), which is reduced with DIBAL in toluene, yielding 6-methyl-4-phenyl-3,4-dihydro-2H-1-benzopyran-2-ol (IV). The reductocondensation of (IV) with diisopropylamine (V) by means of H2 over Pd/C in methanol affords racemic tolterodine (VI), which is finally submitted to optical resolution with L-tartaric acid in dichloromethane/water.

参考文献中间体

合成目标

【1】 Gage, J.R.; Cabaj, J.E. (Pharmacia Corp.); Process to prepare tolterodine. US 5992914; WO 9829402 .

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)	37680	(2E)-3-phenyl-2-propenoic acid; trans-Cinnamic acid; trans-3-Phenylacrylic acid	140-10-3	C₉H₈O₂	详情	详情
(II)	37678	p-cresol	106-44-5	C₇H₈O	详情	详情
(III)	13561	6-Methyl-4-phenyl-2-chromanone		C₁₆H₁₄O₂	详情	详情
(IV)	37679	6-methyl-4-phenyl-2-chromanol		C₁₆H₁₆O₂	详情	详情
(V)	13565	N-Isopropyl-2-propanamine; Bis(isopropyl)amine; N,N-Diisopropylamine	108-18-9	C₆H₁₅N	详情	详情
(VI)	13567	2-[3-(Diisopropylamino)-1-phenylpropyl]-4-methylphenol		C₂₂H₃₁NO	详情	详情

Extended Information