(2S)-(+)-Glycidyl tosylate; (2S)oxiranylmethyl 4-methylbenzenesulfonate -Drug Synthesis Database

【结构式】

【分子编号】16740

【品名】(2S)-(+)-Glycidyl tosylate; (2S)oxiranylmethyl 4-methylbenzenesulfonate

【CA登记号】70987-78-9

【分子式】C₁₀H₁₂O₄S

【分子量】228.26888

【元素组成】C 52.62% H 5.3% O 28.04% S 14.05%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(II)

The reaction of 3,4-difluorophenol (I) with (S)-oxiranylmethyl p-toluenesulfonate ester (II) by means of NaH in DMF gives (S)-(3,4-difluorophenoxymethyl)oxirane (III), which is then condensed with N-(2-benzothiazolyl)-N-methyl-N-(4-piperidyl)amine (IV) by means of Na2CO3 in refluxing isopropanol or butanol/water.

参考文献中间体

合成目标

【1】 Graul, A.; Castañer, J.; Lubeluzole. Drugs Fut 1997, 22, 6, 629.
【2】 Stokbroekx, R.A.; Grauwels, G.A.J. (Janssen Pharmaceutica NV); 4-[(2-Benzothiazolyl)methylamino]-alpha-[(3,4-difluorophenoxy)methyl]-1-piperidineethanol. EP 0501552; EP 0573473; JP 1994505012; US 5434168; WO 9214731 .

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)	16739	3,4-difluorophenol	2713-33-9	C₆H₄F₂O	详情	详情
(II)	16740	(2S)-(+)-Glycidyl tosylate; (2S)oxiranylmethyl 4-methylbenzenesulfonate	70987-78-9	C₁₀H₁₂O₄S	详情	详情
(III)	16741	(2S)-2-[(3,4-difluorophenoxy)methyl]oxirane; 3,4-difluorophenyl (2S)oxiranylmethyl ether		C₉H₈F₂O₂	详情	详情
(IV)	16742	N-(1,3-benzothiazol-2-yl)-N-methyl-N-(4-piperidinyl)amine; N-methyl-N-(4-piperidinyl)-1,3-benzothiazol-2-amine		C₁₃H₁₇N₃S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

The enantiomerically pure sulfoxide was prepared by a different route, starting from the alkylation of hydroxyquinolinone (A) with (S)-glycidyl tosylate (IV) to give the chiral epoxide (V). Ring opening with mercaptoimidazole (I) afforded the enantiomerically rich (R)-mercapto alcohol (VI), which after recrystallization from EtOH provided the pure (R)-isomer. Oxidation with m-chloroperbenzoic acid yielded a diastereomeric mixture of hydroxy sulfoxides (VII). After separation by column chromatography, the required (S)-sulfoxide was converted to mesylate (VIII), and finally reduced with lithium triethylborohydride to afford the target (S)-compound.

参考文献中间体

合成目标

【1】 Nishi, T.; Chu, G.-N.; Okada, M.; Tamura, K.; Unemi, F.; Koga, Y.; Kido, M.; Igawa, T.; Ozeki, Y.; Uno, T.; Synthesis of 2(1H)-quinolinone derivatives and their inhibitory activity on the release of 12(S)-hydroxyeicosatetraenoic acid (12-HETE) from platelets. Chem Pharm Bull 1995, 43, 10, 1724.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	30226	6-Hydroxy-2-oxo-1,2,3,4-tetrahydroquinoline; 6-Hydroxy-3,4-dihydro-2(1H)-quinolinone; 6-Hydroxy-3,4-dihydrocarbostyril		C₉H₉NO₂	详情	详情
(I)	30223	1-(2-methylphenyl)-1H-imidazol-2-ylhydrosulfide; 1-(2-methylphenyl)-1H-imidazole-2-thiol		C₁₀H₁₀N₂S	详情	详情
(IV)	16740	(2S)-(+)-Glycidyl tosylate; (2S)oxiranylmethyl 4-methylbenzenesulfonate	70987-78-9	C₁₀H₁₂O₄S	详情	详情
(V)	30227	6-[(2S)oxiranylmethoxy]-3,4-dihydro-2(1H)-quinolinone		C₁₂H₁₃NO₃	详情	详情
(VI)	30228	6-[((2R)-2-hydroxy-3-[[1-(2-methylphenyl)-1H-imidazol-2-yl]sulfanyl]propyl)oxy]-3,4-dihydro-2(1H)-quinolinone		C₂₂H₂₃N₃O₃S	详情	详情
(VII)	30229	6-[((2R)-2-hydroxy-3-[[1-(2-methylphenyl)-1H-imidazol-2-yl]sulfinyl]propyl)oxy]-3,4-dihydro-2(1H)-quinolinone		C₂₂H₂₃N₃O₄S	详情	详情
(VIII)	30230	(1R)-2-[[1-(2-methylphenyl)-1H-imidazol-2-yl]sulfinyl]-1-[[(2-oxo-1,2,3,4-tetrahydro-6-quinolinyl)oxy]methyl]ethyl methanesulfonate		C₂₃H₂₅N₃O₆S₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(II)

The condensation of indeno[1,2-d]oxazole derivative (I) with (S)-(+)-glycidyl tosylate (II) by means of LiHMDS gives the adduct (III), which is deprotected with HCl to yield the epoxide (IV). Finally, this compound is condensed with the dibenzylpyrrolidone (V) by means of P4 phosphazene base (commercially available) in THF to afford the target amide.

参考文献中间体

合成目标

【1】 Spaltenstein, A.; Cleary, D.G.; Almond, M.R.; Kazmierski, W.M.; Wright, L.L.; Tung, R.D.; Hazen, R.J.; Furfine, E.S.; Salituro, F.G.; Bock, W.J.; Novel inhibitors of HIV protease: Design, synthesis and biological evaluation of picomolar inhibitors containing cyclic P1/P2 scaffolds. Bioorg Med Chem Lett 2000, 10, 11, 1159.
【2】 Askin, D.; Eng, K.K.; Rossen, K.; Purick, R.M.; Wells, K.M.; Volante, R.P.; Reider, P.J.; Highly diastereoselective reaction of a chiral, non-racemic amide enolate with (S)-glycidyl tosylate. Synthesis of the orally active HIV-1 protease inhibitor L-735,524. Tetrahedron Lett 1994, 35, 5, 673-6.

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)	16241	1-[(3aS,8aR)-2,2-dimethyl-8,8a-dihydro-2H-indeno[1,2-d][1,3]oxazol-3(3aH)-yl]-3-phenyl-1-propanone		C₂₁H₂₃NO₂	详情	详情
(II)	16740	(2S)-(+)-Glycidyl tosylate; (2S)oxiranylmethyl 4-methylbenzenesulfonate	70987-78-9	C₁₀H₁₂O₄S	详情	详情
(III)	16243	(2R)-1-[(3aS,8aR)-2,2-dimethyl-8,8a-dihydro-2H-indeno[1,2-d][1,3]oxazol-3(3aH)-yl]-2-benzyl-3-[(2S)oxiranyl]-1-propanone		C₂₄H₂₇NO₃	详情	详情
(IV)	50304	(2R)-2-benzyl-N-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]-3-[(2S)oxiranyl]propanamide		C₂₁H₂₃NO₃	详情	详情
(V)	38974	(3S,5R)-3,5-dibenzyl-2-pyrrolidinone		C₁₈H₁₉NO	详情	详情

Extended Information