Dibromoneopentyl glycol; 2,2-Bis(bromomethyl)-1,3-propanediol -Drug Synthesis Database

【结构式】

【分子编号】12072

【品名】Dibromoneopentyl glycol; 2,2-Bis(bromomethyl)-1,3-propanediol

【CA登记号】3296-90-0

【分子式】C₅H₁₀Br₂O₂

【分子量】261.9412

【元素组成】C 22.93% H 3.85% Br 61.01% O 12.22%

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：(VII)

Zeniplatin can be obtained by two related ways: 1) The reaction of dimethylsulfoxide with potassium tetrachloroplatinate (I) gives bis(dimethylsulfoxide-S,S')dichloroplatinum (II), which is then condensed with silver cyclobutane-1,1-dicarboxylate (III) in water to yield bis(dimethylsulfoxide-S,S')(1,1-cyclobutanedicarboxylato-O,O')platinum (IV). Finally, this compound is treated with 2,2-bis(aminomethyl)-1,3-propanediol (V) in refluxing water. 2) The reaction of potassium tetrachloroplatinate (I) with diamine (V) in water gives [2,2-bis(aminomethyl)-1,3-propanediol-N,N']dichloroplatinum (IV), which is treated with the silver salt (III) as before. The diamine (V) is prepared by reaction of 2,2-bis(bromomethyl)-1,3-propanediol (VII) with sodium azide in hot DMF to give 2,2-bis(azidomethyl)-1,3-propanediol (VIII), which is then reduced with hydrogen over Pt.

参考文献中间体

合成目标

【1】 Grassing Child, R.; Bitha, P.; Hlavka, J.J.; Lin, Y. (Zyma); [2,2-Bis(aminomethyl)-1,3-propanediol-N,N']platinum complexes. AU 8432572; EP 0140830; ES 8802308; GB 2145720; JP 1985149581; US 4665202 .
【2】 Bitha, P.; Hlavka, J.J.; Lin, Y. (American Cyanamid Co.); Synthesis of cisplatinum analogs. EP 0296321 .
【3】 Carvajal, S.G.; Citarella, R.V.; Bitha, P.; et al.; Water-soluble third generation antitumor Pt complexes, [2,2-bis(aminomethyl)-1,3-propanediol-N,N']- [1,1-cyclobutanedicarboxylato(2-)-O,O']Pt(II) and [1,1-cyclobutanedicarboxylato(2-)-O,O']-[tetrahydro-4H-pyran-4,4-dimethanamine-N,N']Pt(II). J Med Chem 1989, 32, 8, 2015.
【4】 Prous, J.; Castaner, J.; Zeniplatin. Drugs Fut 1992, 17, 6, 471.

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)	51693	dipotassium tetrachloroplatinate(2-);potassium tetrachloroplatinate(II);potassium tetrachloroplatinate	10025-99-7	Cl₄K₂Pt	详情	详情
(II)	61657	dichloroplatinum		Cl₂Pt	详情	详情
(III)	12065	Bis(dimethylsulfoxide-S,S')dichloroplatinum		C₆H₆Ag₂O₄	详情	详情
(IV)	12069	Cyclobutane-1,1-dicarboxylic acid platinum salt		C₆H₆O₄Pt	详情	详情
(V)	12070	2,2-Bis(aminomethyl)-1,3-propanediol		C₅H₁₄N₂O₂	详情	详情
(VI)	12071	2,2-Bis(hydroxymethyl)propane-1,3-diamine dichloro platinum complex		C₅H₁₄Cl₂N₂O₂Pt	详情	详情
(VII)	12072	Dibromoneopentyl glycol; 2,2-Bis(bromomethyl)-1,3-propanediol	3296-90-0	C₅H₁₀Br₂O₂	详情	详情
(VIII)	12073	2,2-Bis(azidomethyl)-1,3-propanediol		C₅H₁₀N₆O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

Alkylation of adenine (I) by means of (R)-propylene carbonate (II) in the presence of NaOH in hot DMF provided (R)-9-(2-hydroxypropyl)adenine (III). This was condensed with tosylate (IV) using magnesium tert-butoxide to furnish the alkoxymethylphosphonate (V). Phosphonic acid (VI) was then obtained by hydrolysis of the phosphate ester groups with bromotrimethylsilane. Monophenyl phosphonate (IX) was prepared by either coupling of acid (VI) with phenol (VII) in the presence of DCC or by previous activation of (VI) with SOCl2, and then coupling with phenoxytrimethylsilane (VIII). Further activation of (IX) with SOCl2 to give (X), followed by its condensation with L-alanine isopropyl ester (XI), yielded phosphonamide (XII) as a mixture of diastereomers. The title isomer was then isolated by several alternative procedures, including column chromatography over various supports and fractional crystallization.

参考文献中间体

合成目标

【1】 Prisbe, E.J.; Lee, W.A.; Rohloff, J.C.; Becker, M.W.; Chapman, H.H.; Cihlar, T.; Eisenberg, E.J.; He, G.-X.; Kernan, M.R.; Sparacino, M.L. (Gilead Sciences Inc.); Prodrugs of phosphonate nucleotide analogues and methods for selecting and making same. WO 0208241 .

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)	10343	9H-Purin-6-amine; 9H-Purin-6-ylamine; Adenine	73-24-5	C₅H₅N₅	详情	详情
(II)	19244	(4S)-4-methyl-1,3-dioxolan-2-one		C₄H₆O₃	详情	详情
(III)	19232	(2S)-1-(6-amino-9H-purin-9-yl)-2-propanol		C₈H₁₁N₅O	详情	详情
(IV)	12072	Dibromoneopentyl glycol; 2,2-Bis(bromomethyl)-1,3-propanediol	3296-90-0	C₅H₁₀Br₂O₂	详情	详情
(V)	19246	diethyl [[(1S)-2-(6-amino-9H-purin-9-yl)-1-methylethyl]oxy]methylphosphonate		C₁₃H₂₂N₅O₄P	详情	详情
(VI)	19252	[[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethyl]oxy]methylphosphonic acid		C₉H₁₄N₅O₄P	详情	详情
(VII)	23540	Phenol	108-95-2	C₆H₆O	详情	详情
(VIII)	58583	Trimethylsilylphenoxide; Phenoxytrimethylsilane	1529-17-5	C₉H₁₄OSi	详情	详情
(IX)	58584	phenyl hydrogen {[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethyl]oxy}methylphosphonate		C₁₅H₁₈N₅O₄P	详情	详情
(X)	58585	phenyl {[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethyl]oxy}methylphosphonate chloride		C₁₅H₁₇ClN₅O₃P	详情	详情
(XI)	58586	isopropyl (2S)-2-aminopropanoate		C₆H₁₃NO₂	详情	详情
(XII)	58587	isopropyl (2S)-2-{[({[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethyl]oxy}methyl)(phenoxy)phosphoryl]amino}propanoate		C₂₁H₂₉N₆O₅P	详情	详情

Extended Information