Fesoterodine, SPM-907, Toviaz, -Drug Synthesis Database

【结构式】

【药物名称】Fesoterodine, SPM-907, Toviaz

【化学名称】2-Methylpropionic acid 2-[3-(N,N-diisopropylamino)-1(R)-phenylpropyl]-4-(hydroxymethyl)phenyl ester
　　　　　　Isobutyric acid 2-[3-(diisopropylamino)-1(R)-phenylpropyl]-4-(hydroxymethyl)phenyl ester

【CA登记号】286930-02-7, 345663-07-2 (hydrochloride), 286930-04-9 (hydrochloride hydrate), 286930-03-8 (maleate)

【分子式】C₂₆H₃₇NO₃;C₂₆H₃₇NO₃.C₄H₄O₄

【分子量】411.58969

【开发单位】Schwarz (Originator)

【药理作用】RENAL-UROLOGIC DRUGS, Urinary Incontinence Therapy, Muscarinic M3 Antagonists

合成路线1 合成路线2 合成路线3

合成路线1

The known aminoacid (I) is esterified to (II) employing methanolic H2SO4. Ester group reduction in (II) with LiAlH4 yields alcohol (III). The O-benzyl group of (III) is then removed by catalytic hydrogenation in the presence of Raney nickel, providing phenol (V). Alternatively, compound (III) is converted into diol (V) by O-benzyl group hydrogenolysis, followed by LiAlH4 reduction of the resultant ester (IV). Finally, selective monoesterification of diol (V) with isobutyryl chloride (VI) and triethylamine gives rise to the title compound.

参考文献中间体

【1】 Sorbera, L.A.; Castaner, J.; Leeson, P.A.; Fesoterodine. Drugs Fut 2003, 28, 7, 647.
【2】 Meese, C. (Schwarz Pharma AG); Stable salts of novel derivs. of 3,3-diphenylpropylamines. DE 19955190; JP 2003514018; WO 0135957 .

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)	60854	4-(benzyloxy)-3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]benzoic acid		C₂₉H₃₅NO₃	详情	详情
(II)	60855	methyl 4-(benzyloxy)-3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]benzoate		C₃₀H₃₇NO₃	详情	详情
(III)	60856	{4-(benzyloxy)-3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenyl}methanol		C₂₉H₃₇NO₂	详情	详情
(IV)	60857	methyl 3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]-4-hydroxybenzoate		C₂₃H₃₁NO₃	详情	详情
(V)	60858	2-[(1R)-3-(diisopropylamino)-1-phenylpropyl]-4-(hydroxymethyl)phenol		C₂₂H₃₁NO₂	详情	详情
(VI)	14932	isobutyryl chloride; 2-methylpropanoyl chloride	79-30-1	C₄H₇ClO	详情	详情

合成路线2

参考文献中间体

【1】 Charugundla Kishore, Kumar Udhaya, Patil Rajendra Suryabhan. 2009. An improved process for the preparation of fesoterodine. WO 2009037569.
【2】 Neela Praveen Kumar, Charugundla Kishore, Kumar Udhaya, et al. 2010. Fesoterodine substance of dehydroxy impurity. WO 2010010464.

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)	25313	4-bromophenol	106-41-2	C₆H₅BrO	详情	详情
(II)	67138	6-bromo-4-phenylchroman-2-one	156755-23-6	C₁₅H₁₁BrO₂	详情	详情
(III)	67139	methyl 3-(2-(benzyloxy)-5-bromophenyl)-3-phenylpropanoate		C₂₃H₂₁BrO₃	详情	详情
(IV)	67140	3-(2-(benzyloxy)-5-bromophenyl)-3-phenylpropan-1-ol		C₂₂H₂₁BrO₂	详情	详情
(V)	67141	3-(2-(benzyloxy)-5-bromophenyl)-3-phenylpropyl 4-methylbenzenesulfonate		C₂₉H₂₇BrO₄S	详情	详情
(VI)	67142	3-(2-(benzyloxy)-5-bromophenyl)-N,N-diisopropyl-3-phenylpropan-1-amine		C₂₈H₃₄BrNO	详情	详情
(VII)	67143	(2S,3S)-2,3-bis((4-methylbenzoyl)oxy)succinic acid		C₂₀H₁₈O₈	详情	详情
(VIII)	67144	(S)-3-(2-(benzyloxy)-5-bromophenyl)-N,N-diisopropyl-3-phenylpropan-1-amine (2S,3S)-2,3-bis((4-methylbenzoyl)oxy)succinate		C₂₈H₃₄BrNO.C₂₀H₁₈O₈	详情	详情
(IX)	67145	(S)-3-(2-(benzyloxy)-5-bromophenyl)-N,N-diisopropyl-3-phenylpropan-1-amine		C₂₈H₃₄BrNO	详情	详情
(X)	60854	4-(benzyloxy)-3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]benzoic acid		C₂₉H₃₅NO₃	详情	详情
(XI)	60855	methyl 4-(benzyloxy)-3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]benzoate		C₃₀H₃₇NO₃	详情	详情
(XII)	60856	{4-(benzyloxy)-3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenyl}methanol		C₂₉H₃₇NO₂	详情	详情
(XIII)	60858	2-[(1R)-3-(diisopropylamino)-1-phenylpropyl]-4-(hydroxymethyl)phenol		C₂₂H₃₁NO₂	详情	详情
(XV)	67137	cinnamic acid	140-10-3	C₉H₈O₂	详情	详情

合成路线3

参考文献中间体

【1】 Ahman JB, Dillon BR, Pettman AJ. 2007. Process for the production of benzopyran-2-ol derivatives. WO 2007138440.
【2】 Browne R, Killkell M. 2007. New synthesis of substituted hydroxymethyl phenols. WO 2007137799.
【3】 Ennis S, Drews R, Meese C. 2007. Synthesis of phenolic esters of hydroxymethyl phenols. WO 2007140986.
【4】 Ennis S, Funchs C, Kanzler R, et al. 2007. Shortened synthesis using paraformaldehyde or trioxane. WO 2007114091.

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)	28205	4-hydroxybenzoic acid	99-96-7	C₇H₆O₃	详情	详情
(II)	10251	methyl 4-hydroxybenzoate; Methyl p-hydroxybenzoate	99-76-3	C₈H₈O₃	详情	详情
(III)	67146	2-oxo-4-phenylchroman-6-carboxylic acid		C₁₆H₁₂O₄	详情	详情
(IV)	67147	methyl 2-oxo-4-phenylchroman-6-carboxylate		C₁₇H₁₄O₄	详情	详情
(V)	60857	methyl 3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]-4-hydroxybenzoate		C₂₃H₃₁NO₃	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(2)