DRL-11286, -Drug Synthesis Database

【结构式】

【药物名称】DRL-11286

【化学名称】N-[3-[(3aS)-2,3,3a,4-Tetrahydro-1H-pyrrolo[2,1-c][1,4]benzothiazin-7-yl]-2-oxooxazolidin-5(S)-ylmethyl]thiocarbamic acid O-methyl ester

【CA登记号】

【分子式】C₁₇H₂₁N₃O₃S₂

【分子量】379.50322

【开发单位】Dr. Reddy's Laboratories (Originator)

【药理作用】Antibacterial Drugs, ANTIINFECTIVE THERAPY, Oxazolidinones

合成路线1 合成路线2

合成路线1

Condensation between 1,2-difluoro-4-nitrobenzene (I) and L-prolinol (II) affords the N-aryl prolinol (III). Subsequent conversion of alcohol (III) into bromide (IV) is achieved by treatment with CBr4 and PPh3. Displacement of bromide (IV) with sodium thioacetate, followed by basic hydrolysis of the resultant thioacetate ester (V) leads to thiol (VI). Intramolecular cyclization of (VI) in the presence of NaH generates the pyrrolobenzothiazine system (VII). Catalytic hydrogenation of the nitro group of (VII) gives amine (VIII), which is acylated by benzyl chloroformate to provide carbamate (IX). The lithium anion of carbamate (IX) is condensed with (R)-glycidyl butyrate (X) to furnish oxazolidinone (XI). Then, treatment of alcohol (XI) with methanesulfonyl chloride produces mesylate (XII).

参考文献中间体

【1】 Selvakumar, N.; Reddy, B.Y.; Kumar, G.S.; Khera, M.K.; Srinivas, D.; Kumar, M.S.; Das, J.; Iqbal, J.; Trehan, S.; SAR studies on certain conformationally constrained oxazolidinones. 42nd Intersci Conf Antimicrob Agents Chemother (Sept 27 2002, San Diego) 2002, Abst F-1324.

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)	17013	1,2-difluoro-4-nitrobenzene; 3,4-Difluoronitrobenzene	369-34-6	C₆H₃F₂NO₂	详情	详情
(II)	64118	(2S)pyrrolidinylmethanol		C₅H₁₁NO	详情	详情
(III)	64119	[1-(2-fluoro-4-nitrophenyl)-2-pyrrolidinyl]methanol		C₁₁H₁₃FN₂O₃	详情	详情
(IV)	64120	2-(bromomethyl)-1-(2-fluoro-4-nitrophenyl)pyrrolidine		C₁₁H₁₂BrFN₂O₂	详情	详情
(V)	64121	S-{[1-(2-fluoro-4-nitrophenyl)-2-pyrrolidinyl]methyl} ethanethioate		C₁₃H₁₅FN₂O₃S	详情	详情
(VI)	64122	[1-(2-fluoro-4-nitrophenyl)-2-pyrrolidinyl]methylhydrosulfide; [1-(2-fluoro-4-nitrophenyl)-2-pyrrolidinyl]methanethiol		C₁₁H₁₃FN₂O₂S	详情	详情
(VII)	64123	7-nitro-2,3,3a,4-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzothiazine		C₁₁H₁₂N₂O₂S	详情	详情
(VIII)	64124	2,3,3a,4-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzothiazin-7-ylamine; 2,3,3a,4-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzothiazin-7-amine		C₁₁H₁₄N₂S	详情	详情
(IX)	64125	phenylmethyl 2,3,3a,4-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzothiazin-7-ylcarbamate		C₁₉H₂₀N₂O₂S	详情	详情
(X)	18385	(2R)oxiranylmethyl butyrate;(R)-glycidyl butyrate	60456-26-0	C₇H₁₂O₃	详情	详情
(XI)	64126	3-(2,3,3a,4-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzothiazin-7-yl)-5-(hydroxymethyl)-1,3-oxazolidin-2-one		C₁₅H₁₈N₂O₃S	详情	详情
(XII)	64127	[3-(2,3,3a,4-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzothiazin-7-yl)-2-oxo-1,3-oxazolidin-5-yl]methyl methanesulfonate		C₁₆H₂₀N₂O₅S₂	详情	详情

合成路线2

The mesylate group in (XII) is displaced with NaN3 to yield azide (XIII), which is further reduced to the primary amine (XIV) employing PPh3. Finally, reaction of amine (XIV) with thiophosgene, followed by methanol gives rise to the target thiocarbamate derivative.

参考文献中间体

【1】 Selvakumar, N.; Reddy, B.Y.; Kumar, G.S.; Khera, M.K.; Srinivas, D.; Kumar, M.S.; Das, J.; Iqbal, J.; Trehan, S.; SAR studies on certain conformationally constrained oxazolidinones. 42nd Intersci Conf Antimicrob Agents Chemother (Sept 27 2002, San Diego) 2002, Abst F-1324.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XII)	64127	[3-(2,3,3a,4-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzothiazin-7-yl)-2-oxo-1,3-oxazolidin-5-yl]methyl methanesulfonate	C₁₆H₂₀N₂O₅S₂	详情	详情
(XIII)	64128	3-(2,3,3a,4-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzothiazin-7-yl)-5-(azidomethyl)-1,3-oxazolidin-2-one	C₁₅H₁₇N₅O₂S	详情	详情
(XIV)	64129	5-(aminomethyl)-3-(2,3,3a,4-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzothiazin-7-yl)-1,3-oxazolidin-2-one	C₁₅H₁₉N₃O₂S	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)