1,3-oxazolidin-2-one -Drug Synthesis Database

【结构式】

【分子编号】21456

【品名】1,3-oxazolidin-2-one

【CA登记号】497-25-6

【分子式】C₃H₅NO₂

【分子量】87.07824

【元素组成】C 41.38% H 5.79% N 16.09% O 36.75%

与该中间体有关的原料药合成路线共 5 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5

合成路线1

该中间体在本合成路线中的序号：(XVIII)

The oxidation of the aldehyde group of (XVI) with NaClO2 in tert-butanol affords the corresponding carboxylic acid (XVII), which is condensed with 2-oxazolidinone (XVIII) by means of carbonyldiimidazole (CDI) in THF to give the acyl imidazolide (XIX). The arylation of (XIX) with 3,4,5-trimethoxyphenylmagnesium bromide (XX) in THF yields the expected addition product (XXI), which is cyclized by means of TBAF in hot THF to afford the tetracyclic intermediate (XXII). Isomerization of the cis-lactone ring of (XXII) with LDA in THF affords intermediate (XXIII) with its lactone ring with the correct trans-conformation. Finally, this compound is deprotected with ethyl mercaptane and MgBr2 in ethyl ether to provide the target compound.

参考文献中间体

合成目标

【1】 Berkowitz, D.B.; et al.; Enzyme-assisted asymmetric total synthesis of (-)-podophyllotoxin and (-)-picropodophyllin. J Org Chem 2000, 65, 3, 847.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XVI)	32375	(7R,8R)-7-[[(triisopropylsilyl)oxy]methyl]-8-[[2-(trimethylsilyl)ethoxy]methoxy]-7,8-dihydronaphtho[2,3-d][1,3]dioxole-6-carbaldehyde		C₂₈H₄₆O₆Si₂	详情	详情
(XVII)	32376	(7R,8R)-7-[[(triisopropylsilyl)oxy]methyl]-8-[[2-(trimethylsilyl)ethoxy]methoxy]-7,8-dihydronaphtho[2,3-d][1,3]dioxole-6-carboxylic acid		C₂₈H₄₆O₇Si₂	详情	详情
(XVIII)	21456	1,3-oxazolidin-2-one	497-25-6	C₃H₅NO₂	详情	详情
(XIX)	32377	3-[((7R,8R)-7-[[(triisopropylsilyl)oxy]methyl]-8-[[2-(trimethylsilyl)ethoxy]methoxy]-7,8-dihydronaphtho[2,3-d][1,3]dioxol-6-yl)carbonyl]-1,3-oxazolidin-2-one		C₃₁H₄₉NO₈Si₂	详情	详情
(XX)	32378	bromo(3,4,5-trimethoxyphenyl)magnesium		C₉H₁₁BrMgO₃	详情	详情
(XXI)	32379	3-[((5R,6S,7R,8R)-7-[[(triisopropylsilyl)oxy]methyl]-5-(3,4,5-trimethoxyphenyl)-8-[[2-(trimethylsilyl)ethoxy]methoxy]-5,6,7,8-tetrahydronaphtho[2,3-d][1,3]dioxol-6-yl)carbonyl]-1,3-oxazolidin-2-one		C₄₀H₆₁NO₁₁Si₂	详情	详情
(XXII)	32380	(5R,5aS,8aR,9R)-5-(3,4,5-trimethoxyphenyl)-9-[[2-(trimethylsilyl)ethoxy]methoxy]-5,8,8a,9-tetrahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-6(5aH)-one		C₂₈H₃₆O₉Si	详情	详情
(XXIII)	32381	(5R,5aR,8aR,9R)-5-(3,4,5-trimethoxyphenyl)-9-[[2-(trimethylsilyl)ethoxy]methoxy]-5,8,8a,9-tetrahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-6(5aH)-one		C₂₈H₃₆O₉Si	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

The synthesis of the intermediate (chlorophenyl)piperazinone (VIII) has been reported by two procedures. The hydrochloride salt prepared from 3-chloroaniline (I) was treated with 2-oxazolidinone (II) at 160 C to produce the aryl ethylenediamine (III), which was subsequently protected as the N-Boc derivative (IV). Acylation of aniline (IV) with chloroacetyl chloride (V) gave the chloroacetamide (VI). This was then cyclized to the piperazinone (VII) by treatment with K2CO3 in hot DMF. Further acid deprotection of the Boc group of (VII) afforded the intermediate (VIII).

参考文献中间体

合成目标

【1】 Anthony, N.J.; Ciccarone, T.M.; Gomez, R.P.; Hutchinson, J.H.; Williams, T.M.; Dinsmore, C.J.; Stokker, G.E. (Merck & Co., Inc.); Inhibitors of farnesyl-protein transferase. EP 0820445; JP 1998511098; US 5856326; WO 9630343 .
【2】 Williams, T.M.; Dinsmore, C.J.; Hutchinson, J.H. (Merck & Co., Inc.); Inhibitors of prenyl-protein transferase. EP 1014984; WO 9909985 .

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)	25239	3-chloroaniline; 3-chlorophenylamine	108-42-9	C₆H₆ClN	详情	详情
(II)	21456	1,3-oxazolidin-2-one	497-25-6	C₃H₅NO₂	详情	详情
(III)	37091			C₇H₅Cl₂FNO₂P	详情	详情
(IV)	47286	tert-butyl 2-(3-chloroanilino)ethylcarbamate		C₁₃H₁₉ClN₂O₂	详情	详情
(V)	11296	2-Chloroacetyl chloride; Chloroacetic chloride	79-04-9	C₂H₂Cl₂O	详情	详情
(VI)	47287	tert-butyl 2-[3-chloro(2-chloroacetyl)anilino]ethylcarbamate		C₁₅H₂₀Cl₂N₂O₃	详情	详情
(VII)	47288	tert-butyl 4-(3-chlorophenyl)-3-oxo-1-piperazinecarboxylate		C₁₅H₁₉ClN₂O₃	详情	详情
(VIII)	47289	1-(3-chlorophenyl)-2-piperazinone		C₁₀H₁₁ClN₂O	详情	详情

合成路线3

该中间体在本合成路线中的序号：(IV)

Photochemical bromination of 7-methylcoumarin (I) using N-bromosuccinimide and azobis(isobutyronitrile) provided the benzylic bromide (II). N-Phenyl ethylenediamine (V) was prepared by reaction between aniline (III) and oxazolidone (IV) at 140 C. Then, alkylation of amine (V) with bromide (II) in the presence of K2CO3 in refluxing acetonitrile provided the title compound.

参考文献中间体

合成目标

【1】 Kesten, S.R.; et al.; Design, synthesis, and evaluation of coumarins as potent and selective dopamine D4 antagonists. 216th ACS Natl Meet (Aug. 23-27, Boston) 1998, Abst MEDI 123.
【2】 Johnson, S.J.; Heffner, T.G.; Kesten, S.R.; Wise, L.D.; Wright, J.L.; Pugsley, T.A.; Design, synthesis, and evaluation of chromen-2-ones as potent and selective human dopamine D4 antagonists. J Med Chem 1999, 42, 18, 3718.

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)	21453	7-methyl-2H-chromen-2-one	2445-83-2	C₁₀H₈O₂	详情	详情
(II)	21454	7-(bromomethyl)-2H-chromen-2-one		C₁₀H₇BrO₂	详情	详情
(III)	12294	Aniline; Phenylamine	62-53-3	C₆H₇N	详情	详情
(IV)	21456	1,3-oxazolidin-2-one	497-25-6	C₃H₅NO₂	详情	详情
(V)	21457	N(1)-phenyl-1,2-ethanediamine; N-(2-aminoethyl)-N-phenylamine	1664-40-0	C₈H₁₂N₂	详情	详情

合成路线4

该中间体在本合成路线中的序号：(III)

Acid-catalyzed condensation of ethanolamine (I) with urea (II) produced oxazolidinone (III). Subsequent reaction of (III) with triethyloxonium fluoborate yielded ethoxyoxazoline (IV). This was finally condensed with 2-(3,4-dimethoxyphenyl)- ethylamine to afford the title compound, which was isolated as the hydrochloride salt.

参考文献中间体

合成目标

【1】 Xu, J.Y.; et al.; Synthesis of imidazoline, oxazoline derivatives and antihypertensive activity. J Chin Pharm Univ 1998, 29, 5, 336.

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)	10259	Ethanol amine;Ethanolamine;2-Aminoethanol; 2-Amino-1-ethanol；2-Aminoethyl alcohol	141-43-5	C₂H₇NO	详情	详情
(II)	19310	urea	57-13-6	CH₄N₂O	详情	详情
(III)	21456	1,3-oxazolidin-2-one	497-25-6	C₃H₅NO₂	详情	详情
(IV)	25692	4,5-dihydro-1,3-oxazol-2-yl ethyl ether; 2-ethoxy-4,5-dihydro-1,3-oxazole		C₅H₉NO₂	详情	详情
(V)	10098	2-(3,4-Dimethoxyphenyl)-1-ethanamine; 3,4-Dimethoxyphenethylamine; 2-(3,4-Dimethoxyphenyl)ethylamine	120-20-7	C₁₀H₁₅NO₂	详情	详情

合成路线5

该中间体在本合成路线中的序号：(II)

Condensation of p-anisidine (I) with 2-oxazolidinone (II) in hot 2-(2-methoxyethoxy)ethanol affords the N-aryl ethanediamine (III). This is then coupled with the succinimidyl ester of N-Z-L-leucine (IV) to furnish amide (V). The N-carbobenzoxy group of (V) is further removed by catalytic hydrogenation, providing amine (VI), which is finally acylated by 4-(benzyloxy)benzoic acid (VII) by means of HATU to yield the title compound.

参考文献中间体

合成目标

【1】 Altmann, E.; Renaud, J.; Green, J.; Farley, D.; Cutting, B.; Jahnke, W.; Arylaminoethyl amides as novel non-covalent cathepsin K inhibitors. J Med Chem 2002, 45, 12, 2352.
【2】 Missbach, M.; Altmann, E.; Lattmann, R.; Renaud, J. (Novartis AG); Arylaminoalkylamides. WO 0048993 .

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)	10478	p-Anisidine; 4-Methoxyaniline; 4-Methoxyphenylamine	104-94-9	C₇H₉NO	详情	详情
(II)	21456	1,3-oxazolidin-2-one	497-25-6	C₃H₅NO₂	详情	详情
(III)	61030	N-(2-aminoethyl)-N-(4-methoxyphenyl)amine; N~1~-(4-methoxyphenyl)-1,2-ethanediamine		C₉H₁₄N₂O	详情	详情
(IV)	61031	benzyl (1S)-1-{[(2,5-dioxo-1-pyrrolidinyl)oxy]carbonyl}-3-methylbutylcarbamate		C₁₈H₂₂N₂O₆	详情	详情
(V)	61032	benzyl (1S)-1-({[2-(4-methoxyanilino)ethyl]amino}carbonyl)-3-methylbutylcarbamate		C₂₃H₃₁N₃O₄	详情	详情
(VI)	61033	(2S)-2-amino-N-[2-(4-methoxyanilino)ethyl]-4-methylpentanamide		C₁₅H₂₅N₃O₂	详情	详情
(VII)	61034	4-(benzyloxy)benzoic acid		C₁₄H₁₂O₃	详情	详情

Extended Information