【结 构 式】 |
【分子编号】55952 【品名】benzyl 5-[(5R)-5-(hydroxymethyl)-2-oxo-1,3-oxazolidin-3-yl]-2-methyl-1-indolinecarboxylate 【CA登记号】 |
【 分 子 式 】C21H22N2O5 【 分 子 量 】382.41616 【元素组成】C 65.96% H 5.8% N 7.33% O 20.92% |
合成路线1
该中间体在本合成路线中的序号:(VII)2-Methylindole (I) was nitrated employing NaNO3 in H2SO4 and the resultant 5-nitroindole (II) was further reduced to the corresponding indoline (III) by means of NaBH3CN in the presence of HOAc. Catalytic hydrogenation of the nitro group of (III) over Pd/C furnished diamine (IV), which was converted to the bis-carbamate (V) by treatment with benzyl chloroformate. Oxazolidinone (VII) was then obtained by condensation of carbamate (V) with (R)-glycidyl butyrate (VI) in the presence of BuLi at -78 C. After conversion of alcohol (VII) to the corresponding nosylate (VIII), displacement of its sulfonate group with ammonium hydroxide gave rise to the primary amine (IX). Acetylation of amine (IX), followed by hydrogenolysis of the remaining N-benzyloxycarbonyl group, yielded acetamide (X). The indoline N of (X) was then acylated by acetoxyacetyl chloride (XI) to produce amide (XII). The title compound was then obtained by smooth hydrolysis of the acetoxy group of (XII) with K2CO3, followed by separation of the resultant mixture of diastereoisomers by chiral HPLC.
【1】 Genin, M.J.; Barbachyn, M.R.; Grega, K.C.; et al.; The potentiating effect of remote chirality on the antibacterial activity of a series of 2-substituted indolinyl phenyloxazolidinones. 41st Intersci Conf Antimicrob Agents Chemother (Dec 16 2001, Chicago) 2001, Abst F-1042. |
【2】 Hester, J.B. Jr.; Barbachyn, M.R.; Johnson, P.D.; Genin, M.J. (Pharmacia Corp.); Bicyclic oxazolidinones as antibacterial agent. EP 1181288; US 6387896; WO 0073301 . |
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) | 28747 | 2-methyl-1H-indole | 95-20-5 | C9H9N | 详情 | 详情 |
(II) | 55948 | 2-methyl-5-nitro-1H-indole; 2-Methyl-5-nitroindole | 7570-47-0 | C9H8N2O2 | 详情 | 详情 |
(III) | 55949 | 2-methyl-5-nitroindoline | C9H10N2O2 | 详情 | 详情 | |
(IV) | 55950 | 2-methyl-2,3-dihydro-1H-indol-5-ylamine; 2-methyl-5-indolinamine | C9H12N2 | 详情 | 详情 | |
(V) | 55951 | benzyl 5-{[(benzyloxy)carbonyl]amino}-2-methyl-1-indolinecarboxylate | C25H24N2O4 | 详情 | 详情 | |
(VI) | 18385 | (2R)oxiranylmethyl butyrate;(R)-glycidyl butyrate | 60456-26-0 | C7H12O3 | 详情 | 详情 |
(VII) | 55952 | benzyl 5-[(5R)-5-(hydroxymethyl)-2-oxo-1,3-oxazolidin-3-yl]-2-methyl-1-indolinecarboxylate | C21H22N2O5 | 详情 | 详情 | |
(VIII) | 55953 | benzyl 2-methyl-5-[(5R)-5-({[(3-nitrophenyl)sulfonyl]oxy}methyl)-2-oxo-1,3-oxazolidin-3-yl]-1-indolinecarboxylate | C27H25N3O9S | 详情 | 详情 | |
(IX) | 55954 | benzyl 5-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]-2-methyl-1-indolinecarboxylate | C21H23N3O4 | 详情 | 详情 | |
(X) | 55955 | N-{[(5S)-3-(2-methyl-2,3-dihydro-1H-indol-5-yl)-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide | C15H19N3O3 | 详情 | 详情 | |
(XI) | 10456 | Acetoxiacetil chloride; 2-chloro-2-oxoethyl acetate | 13831-31-7 | C4H5ClO3 | 详情 | 详情 |
(XII) | 55956 | 2-(5-{(5S)-5-[(acetylamino)methyl]-2-oxo-1,3-oxazolidin-3-yl}-2-methyl-2,3-dihydro-1H-indol-1-yl)-2-oxoethyl acetate | C19H23N3O6 | 详情 | 详情 |