4'-(hydroxymethyl)[1,1'-biphenyl]-2-carbonitrile -Drug Synthesis Database

【结构式】

【分子编号】37265

【品名】4'-(hydroxymethyl)[1,1'-biphenyl]-2-carbonitrile

【CA登记号】

【分子式】C₁₄H₁₁NO

【分子量】209.24748

【元素组成】C 80.36% H 5.3% N 6.69% O 7.65%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(II)

This compound has been obtained by two related ways: 1) The hydrolysis of 4'-(bromomethyl)biphenyl-2-carbonitrile (I) with NaOAc in refluxing acetic acid gives the corresponding carbinol (II), which is oxidized with oxalyl chloride in DMSO/dichloromethane yielding the aldehyde (III). The reductocondensation of (III) with L-valine methyl ester (IV) by means of NaBH4CN in THF affords the N-alkylated valine (V), which is acylated with pentanoyl chloride (VI) and TEA in dichloromethane providing the pentanamide (VII). The reaction of the CN group of (VII) with tributyltin azide in refluxing xylene gives the tetrazol derivative (VIII). Finally, the ester group of (VIII) is hydrolyzed with NaOH to furnish the target compound. 2) L-valine methyl ester (IV) can be condensed directly with the bromo-methyl derivative (I) by means of DIEA in dichloromethane giving the N-alkylated valine (V) already reported.

参考文献中间体

合成目标

【1】 Buhlmayer, P.; Ostermayer, F.; Schmidlin, T. (Novartis AG); Acyl cpds.. EP 0443983; JP 1992235149; US 5399578; US 5965592 .
【2】 Buhlmayer, P.; et al.; Valsartan, a potent, orally active angiotensin II antagonist developed from the structurally new amino acid series. Bioorg Med Chem Lett 1994, 4, 1, 29.

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)	15332	4'-(bromomethyl)[1,1'-biphenyl]-2-carbonitrile; 4'-bromomethyl-2-cyanobiphenyl	114772-54-2	C₁₄H₁₀BrN	详情	详情
(II)	37265	4'-(hydroxymethyl)[1,1'-biphenyl]-2-carbonitrile		C₁₄H₁₁NO	详情	详情
(III)	37266	4'-formyl[1,1'-biphenyl]-2-carbonitrile		C₁₄H₉NO	详情	详情
(IV)	16613	methyl (2S)-2-amino-3-methylbutanoate		C₆H₁₃NO₂	详情	详情
(V)	37267	methyl (2S)-2-[[(2'-cyano[1,1'-biphenyl]-4-yl)methyl]amino]-3-methylbutanoate		C₂₀H₂₂N₂O₂	详情	详情
(VI)	15116	pentanoyl chloride; valeryl chloride	638-29-9	C₅H₉ClO	详情	详情
(VII)	37268	methyl (2S)-2-[[(2'-cyano[1,1'-biphenyl]-4-yl)methyl](pentanoyl)amino]-3-methylbutanoate		C₂₅H₃₀N₂O₃	详情	详情
(VIII)	37269	methyl (2S)-3-methyl-2-(pentanoyl[[2'-(1H-1,2,3,4-tetraazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]amino)butanoate		C₂₅H₃₁N₅O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

The title ternary ligand technetium-99m complex was formed as a mixture of two isomeric forms by reaction of the hydrazinonicotinamide-derivatized cyclic peptide (I) with trisodium triphenylphosphine-3,3',3''-trisulfonate (II) and tricine (III) in the presence of 99mTc pertechnetate and SnCl2. The 99Tc analogue was similarly prepared for spectroscopic characterization by using (n-Bu4N)(99TcOCl4) or (NH4)(99TcO4).

参考文献中间体

合成目标

【1】 Liu, S.; et al.; Technetium complexes of a hydrazinonicotinamide-conjugated cyclic peptide and 2-hydrazinopyridine: synthesis and characterization. Inorg Chem 1999, 38, 6, 1326.
【2】 Liu, S.; Edwards, D.S. (DuPont Pharmaceuticals Co.); Ternary radiopharmaceutical complexes. EP 0995761; US 5744120; WO 9631243 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	48084	2-[(5S,11S,14R)-11-(3-[[amino(imino)methyl]amino]propyl)-19-[(6-[[(6-hydrazino-3-pyridinyl)carbonyl]amino]hexanoyl)amino]-14-isopropyl-12-methyl-4,7,10,13,16-pentaoxo-3,6,9,12,15-pentaazabicyclo[15.3.1]henicosa-1(21),17,19-trien-5-yl]acetic acid	C₃₈H₅₅N₁₃O₉	详情	详情
(II)	37264	trisodium 3-[bis(3-sulfonatophenyl)phosphino]benzenesulfonate	C₁₈H₁₂Na₃O₉PS₃	详情	详情
(III)	37265	4'-(hydroxymethyl)[1,1'-biphenyl]-2-carbonitrile	C₁₄H₁₁NO	详情	详情

合成路线3

该中间体在本合成路线中的序号：(III)

The title compound was then obtained by complexation of hydrazone (IX) with phosphine (II) and tricine (III) in the presence of Na99mTcO4 and SnCl2. Under these conditions, the hydrazone protecting group hydrolyzed to the required hydrazine. Some shortcomings caused by SnCl2 could be omitted using a non-SnCl2-containing formulation in the presence of mannitol and pluronic acid as surfactant agents.

参考文献中间体

合成目标

【1】 Edwards, D.S.; et al.; 99mTc-Labeling of hydrazones of a hydrazinonicotinamide conjugated cyclic peptide. Bioconjugate Chem 1999, 10, 5, 803.
【2】 Liu, S.; et al.; Towards developing A non-SnCl2 formulation for RP444, a new radiopharmaceutical for thrombus imaging. J Pharm Sci 2001, 90, 2, 114.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(II)	37264	trisodium 3-[bis(3-sulfonatophenyl)phosphino]benzenesulfonate	C₁₈H₁₂Na₃O₉PS₃	详情	详情
(III)	37265	4'-(hydroxymethyl)[1,1'-biphenyl]-2-carbonitrile	C₁₄H₁₁NO	详情	详情
(IX)	48090	sodium 2-[[(E)-2-(5-[[(6-[[(4R,7S,13S)-7-(3-[[amino(imino)methyl]amino]propyl)-13-(carboxymethyl)-4-isopropyl-6-methyl-2,5,8,11,14-pentaoxo-3,6,9,12,15-pentaazabicyclo[15.3.1]henicosa-1(21),17,19-trien-19-yl]amino]-6-oxohexyl)amino]carbonyl]-2-pyridinyl)hydrazono]methyl]benzenesulfonate	C₄₅H₅₈N₁₃NaO₁₂S	详情	详情

合成路线4

该中间体在本合成路线中的序号：(I)

The reaction of dibenzazepine (I) with the chiral epichlorohydrin (II) by means of NaNH2 in refluxing benzene gives the adduct (III), which is finally treated with isopropylamine (IV) to yield the target isopropanol derivative.

参考文献中间体

合成目标

【1】 Levy, O.; et al.; A new class of antiarrhythmic-defibrillatory agents. Bioorg Med Chem Lett 2001, 11, 22, 2921.

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)	37265	4'-(hydroxymethyl)[1,1'-biphenyl]-2-carbonitrile		C₁₄H₁₁NO	详情	详情
(II)	38067	(2R)-2-(Chloromethyl)oxirane; (R)-Epichlorohydrin	51594-55-9	C₃H₅ClO	详情	详情
(III)	54451	5-[(2R)oxiranylmethyl]-10,11-dihydro-5H-dibenzo[b,f]azepine		C₁₇H₁₇NO	详情	详情
(IV)	23933	2-Propanamine; Isopropylamine	75-31-0	C₃H₉N	详情	详情

Extended Information