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【结 构 式】 
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【分子编号】55095 【品名】ethyl 2-propynyl(2-pyrazinylmethyl)carbamate 【CA登记号】 |
【 分 子 式 】C11H13N3O2 【 分 子 量 】219.24324 【元素组成】C 60.26% H 5.98% N 19.17% O 14.6% |
合成路线1
该中间体在本合成路线中的序号：(I)Intramolecular Diels-Alder reaction of the N-pyrazinylmethyl-N-propargyl carbamate (I), with subsequent extrusion of HCN, gave rise to a mixture of the isomeric pyrrolopyridines (II) and (III). Acidic hydrolysis of the pyrrolo[3,4-b]pyridine carbamate (III) provided the bicyclic amine (IV). This was condensed with 3,4-difluoronitrobenzene (V) to give the aryl amine (VI). Catalytic hydrogenation of the nitro group of (VI) yielded aniline (VII), which was converted to the benzyl carbamate (VIII) upon treatment with benzyl chloroformate. The chiral oxazolidinone (X) was then obtained by condensation of the lithium salt of carbamate (VIII) with (R)-glycidyl butyrate (IX) at -78 C. Conversion of alcohol (X) to mesylate (XI), and subsequent mesylate displacement with NaN3 in hot DMF, furnished azide (XII). Finally, hydrogenation of azide (XII) to the corresponding amine, followed by acylation with Ac2O, led to the target acetamide.
| 【1】 Paget, S.; Weidner-Wells, M.; Hlasta, D.; et al.; Synthesis and antibacterial activity of pyrrolopyridine-substituted oxazolidinones. 41st Intersci Conf Antimicrob Agents Chemother (Dec 16 2001, Chicago) 2001, Abst F-1048. |
| 【2】 Hlasta, D.; Paget, S. (Ortho-McNeil Pharmaceutical, Inc.); Antibacterial heterobicyclic substd. phenyl oxazolidinones. EP 1206469; US 6413981; WO 0142242 . |
| 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) | 55095 | ethyl 2-propynyl(2-pyrazinylmethyl)carbamate | C11H13N3O2 | 详情 | 详情 | |
| (II) | 55096 | ethyl 1,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxylate | C10H12N2O2 | 详情 | 详情 | |
| (III) | 55097 | ethyl 5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-carboxylate | C10H12N2O2 | 详情 | 详情 | |
| (IV) | 55098 | 6,7-dihydro-5H-pyrrolo[3,4-b]pyridine | C7H8N2 | 详情 | 详情 | |
| (V) | 17013 | 1,2-difluoro-4-nitrobenzene; 3,4-Difluoronitrobenzene | 369-34-6 | C6H3F2NO2 | 详情 | 详情 |
| (VI) | 55099 | 6-(2-fluoro-4-nitrophenyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine | C13H10FN3O2 | 详情 | 详情 | |
| (VII) | 55100 | 4-(5,7-dihydro-6H-pyrrolo[3,4-b]pyridin-6-yl)-3-fluoroaniline; 4-(5,7-dihydro-6H-pyrrolo[3,4-b]pyridin-6-yl)-3-fluorophenylamine | C13H12FN3 | 详情 | 详情 | |
| (VIII) | 55101 | benzyl 4-(5,7-dihydro-6H-pyrrolo[3,4-b]pyridin-6-yl)-3-fluorophenylcarbamate | C21H18FN3O2 | 详情 | 详情 | |
| (IX) | 18385 | (2R)oxiranylmethyl butyrate;(R)-glycidyl butyrate | 60456-26-0 | C7H12O3 | 详情 | 详情 |
| (X) | 55102 | (5R)-3-[4-(5,7-dihydro-6H-pyrrolo[3,4-b]pyridin-6-yl)-3-fluorophenyl]-5-(hydroxymethyl)-1,3-oxazolidin-2-one | C17H16FN3O3 | 详情 | 详情 | |
| (XI) | 55103 | {(5R)-3-[4-(5,7-dihydro-6H-pyrrolo[3,4-b]pyridin-6-yl)-3-fluorophenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl methanesulfonate | C18H18FN3O5S | 详情 | 详情 | |
| (XII) | 55104 | (5R)-5-(azidomethyl)-3-[4-(5,7-dihydro-6H-pyrrolo[3,4-b]pyridin-6-yl)-3-fluorophenyl]-1,3-oxazolidin-2-one | C17H15FN6O2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)Intramolecular Diels-Alder reaction of the N-pyrazinylmethyl-N-propargyl carbamate (I), with subsequent extrusion of HCN, gave rise to a mixture of the isomeric pyrrolopyridines (II) and (III). Acidic hydrolysis of the pyrrolo[3,4-c]pyridine carbamate (III) provided the bicyclic amine (IV). This was condensed with 3,4-difluoronitrobenzene (V) to give the aryl amine (VI). Catalytic hydrogenation of the nitro group of (V) yielded aniline (VII), which was converted to the benzyl carbamate (VIII) upon treatment with benzyl chloroformate. The chiral oxazolidinone (X) was then obtained by condensation of the lithium salt of carbamate (VIII) with (R)-glycidyl butyrate (IX) at -78 C. Conversion of alcohol (X) to mesylate (XI), and subsequent mesylate displacement with NaN3 in hot DMF, furnished azide (XII). Finally, hydrogenation of azide (XII) to the corresponding amine, followed by acylation with Ac2O, led to the target acetamide.
| 【1】 Paget, S.; Weidner-Wells, M.; Hlasta, D.; et al.; Synthesis and antibacterial activity of pyrrolopyridine-substituted oxazolidinones. 41st Intersci Conf Antimicrob Agents Chemother (Dec 16 2001, Chicago) 2001, Abst F-1048. |
| 【2】 Hlasta, D.; Paget, S. (Ortho-McNeil Pharmaceutical, Inc.); Antibacterial heterobicyclic substd. phenyl oxazolidinones. EP 1206469; US 6413981; WO 0142242 . |
| 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) | 55095 | ethyl 2-propynyl(2-pyrazinylmethyl)carbamate | C11H13N3O2 | 详情 | 详情 | |
| (II) | 55096 | ethyl 1,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxylate | C10H12N2O2 | 详情 | 详情 | |
| (III) | 55097 | ethyl 5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-carboxylate | C10H12N2O2 | 详情 | 详情 | |
| (IV) | 55105 | 2,3-dihydro-1H-pyrrolo[3,4-c]pyridine | C7H8N2 | 详情 | 详情 | |
| (V) | 17013 | 1,2-difluoro-4-nitrobenzene; 3,4-Difluoronitrobenzene | 369-34-6 | C6H3F2NO2 | 详情 | 详情 |
| (VI) | 55106 | 2-(2-fluoro-4-nitrophenyl)-2,3-dihydro-1H-pyrrolo[3,4-c]pyridine | C13H10FN3O2 | 详情 | 详情 | |
| (VII) | 55107 | 4-(1,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2-yl)-3-fluorophenylamine; 4-(1,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2-yl)-3-fluoroaniline | C13H12FN3 | 详情 | 详情 | |
| (VIII) | 55108 | benzyl 4-(1,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2-yl)-3-fluorophenylcarbamate | C21H18FN3O2 | 详情 | 详情 | |
| (IX) | 18385 | (2R)oxiranylmethyl butyrate;(R)-glycidyl butyrate | 60456-26-0 | C7H12O3 | 详情 | 详情 |
| (X) | 55109 | (5R)-3-[4-(1,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2-yl)-3-fluorophenyl]-5-(hydroxymethyl)-1,3-oxazolidin-2-one | C17H16FN3O3 | 详情 | 详情 | |
| (XI) | 55110 | {(5R)-3-[4-(1,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2-yl)-3-fluorophenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl methanesulfonate | C18H18FN3O5S | 详情 | 详情 | |
| (XII) | 55111 | (5R)-5-(azidomethyl)-3-[4-(1,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2-yl)-3-fluorophenyl]-1,3-oxazolidin-2-one | C17H15FN6O2 | 详情 | 详情 |