acetone -Drug Synthesis Database

【结构式】

【分子编号】53313

【品名】acetone

【CA登记号】67-64-1

【分子式】C₃H₆O

【分子量】58.08004

【元素组成】C 62.04% H 10.41% O 27.55%

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：(II)

The reaction of 14C-labeled acetone (I) with O-benzylhydroxylamine (II) and pyridine in refluxing ethanol gives the corresponding oxime (III), which is methylated with MeLi and BF3.Et2O in toluene to yield labeled N-tert-butyl-O-benzylhydroxylamine (IV). The deprotection of (IV) by hydrogenation with H2 over Pd/C in methanol affords N-tert-butylhydroxylamine (V), which is finally condensed with benzaldehyde 2,4-disulfonic acid sodium salt (VI) in HOAc/water to give rise to the target imine oxide.

参考文献中间体

合成目标

【1】 Johansson, R.; Werner, R.; Syntheses of two [14C]-labeled disodium 4-[(N-tert-butylimino)methyl]benzene-1,3-disulfonate N-oxides. J Label Compd Radiopharm 2000, 43, 13, 1265.

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)	14640	O-benzylhydroxylamine; 1-[(aminooxy)methyl]benzene	622-33-3	C₇H₉NO	详情	详情
(II)	23199	2-Propanone; Acetone; beta-ketopropane; chevron acetone;propan-2-one； Dimethyl formaldehyde; Dimethyl ketone; dimethylketal; Ketone propane; Methyl ketone; Propanone; Pyroacetic acid; Pyroacetic ether	67-64-1	C₃H₆O	详情	详情
(II)	53313	acetone	67-64-1	C₃H₆O	详情	详情
(III)	53314	acetone O-benzyloxime	n/a	C₁₀H₁₃NO	详情	详情
(III)	53315	acetone O-benzyloxime	n/a	C₁₀H₁₃NO	详情	详情
(IV)	53316	1-{[(tert-butylamino)oxy]methyl}benzene; O-benzyl-N-(tert-butyl)hydroxylamine	n/a	C₁₁H₁₇NO	详情	详情
(IV)	53317	O-benzyl-N-(tert-butyl)hydroxylamine; 1-{[(tert-butylamino)oxy]methyl}benzene	n/a	C₁₁H₁₇NO	详情	详情
(V)	35455	N-(tert-butyl)hydroxylamine; 2-(hydroxyamino)-2-methylpropane		C₄H₁₁NO	详情	详情
(V)	53318	2-(hydroxyamino)-2-methylpropane; N-(tert-butyl)hydroxylamine	16649-50-6	C₄H₁₁NO	详情	详情
(VI)	37311	Benzaldehyde-2,4-disulfonic acid disodium; disodium 4-formyl-1,3-benzenedisulfonate	33513-44-9	C₇H₄Na₂O₇S₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XII)

Esterification of (R)-2-aminobutyric acid (X) with MeOH by means of SOCl2 and trimethyl orthoformate, followed by reductive alkylation of the resulting amino ester (XI) with acetone (XII) and NaBH(OAc)3, and treatment with HCl, gives methyl (R)-2-isopropylamino)butyrate hydrochloride (XIII). Basification of amino ester hydrochloride (XIII) with NaOH in cyclohexane/H2O, and subsequent condensation of the obtained free base with 2,4-dichloro-5-nitropyrimidine (XIV) in the presence of NaHCO3 in refluxing cyclohexane, yields the Npyrimidinyl amino ester (XV). Reductive cyclization of compound (XV) by catalytic hydrogenation in the presence of Pt/C and VO(acac)2 in THF gives pteridinone (XVI), which is finally methylated by heating with Me2CO3 in an autoclave in the presence of K2CO3 .

参考文献中间体

合成目标

【1】 Grauert, M., Linz, G., Schmid, R., Sieger, P. (Boehringer Ingelheim Pharma GmbH & Co. KG). Trihydrochloride forms of a dihydropteridinone derivative and process for preparation. WO 2007090844.
【2】 Linz, G., Sieger, P., Schmid, R., Goepper, S. (Boehringer International GmbH). Crystalline form of a dihydropteridinone derivative. WO 2009019205.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IX)	68535	(R)-2-chloro-7-ethyl-8-isopropyl-5-methyl-7,8-dihydropteridin-6(5H)-one		C₁₂H₁₇ClN₄O	详情	详情
(X)	68536	(R)-2-aminobutyric acid		C₄H₉NO₂	详情	详情
(XI)	68537	(R)-methyl 2-aminobutanoate hydrochloride		C₄H₉NO₂.HCl	详情	详情
(XII)	53313	acetone	67-64-1	C₃H₆O	详情	详情
(XIII)	68538	(R)-methyl 2-(isopropylamino)butanoate hydrochloride;methyl (R)-2-isopropylamino)butyrate hydrochloride		C₈H₁₇NO₂.HCl	详情	详情
(XIV)	68539	2,4-dichloro-5-nitropyrimidine	49845-33-2	C₄HCl₂N₃O₂	详情	详情
(XV)	68540	(R)-methyl 2-((2-chloro-5-nitropyrimidin-4-yl)(isopropyl)amino)butanoate		C₁₂H₁₇ClN₄O₄	详情	详情
(XVI)	68541	(R)-2-chloro-7-ethyl-8-isopropyl-7,8-dihydropteridin-6(5H)-one		C₁₁H₁₅ClN₄O	详情	详情

Extended Information