| 摘要 |
A process for producing a diazabicyclooctane derivative represented by Formula (IV) and intermediates thereof by carrying out the following steps:;;wherein P is an NH protecting group capable of being removed with acid; R1 is 2,5-dioxopyrrolidin-1-yl, 1,3-dioxo-3a,4,7,7a-tetrahydro-1H-isoindol-2(3H)-yl, 1,3-dioxohexahydro-1H-isoindol-2(3H)-yl, or 3,5-dioxo-4-azatricyclo[5.2.1.02.6]dec-8-en-4-yl; R2 is hydrogen, ClCO— or Cl3COCO—; R3 is C1-6 alkyl or heterocyclyl, or forms a 3- to 7-membered heterocyclic ring together with the —O—NH— to which it is attached; and OBn is benzyloxy. |
| 主权项 |
1. A process for producing a compound represented by Formula (IV), comprising: reacting a compound represented by the following Formula (I): with R1OH selected from 1-hydroxypyrrolidine-2,5-dione, 2-hydroxy-3a,4,7,7a-tetrahydro-1H-isoindol-1,3(2H)-dione, 2-hydroxyhexahydro-1H-isoindol-1,3(2H)-dione, and 4-hydroxy-4-azatricyclo [5.2.1.02,6]dec-8-ene-3,5-dione followed by allowing a carbonylating agent selected from phosgene, diphosgene and triphosgene to act thereon to obtain a compound represented by the following Formula (II): removing a protecting group P and treating with a base to obtain a compound represented by the following Formula (III): and reacting with a compound: R3ONH2 to produce the compound represented by the following general Formula (IV): (in the aforementioned Formulas (I), (II), (III) and (IV), OBn is benzyloxy, P is an NH protecting group capable of being removed with acid, R1 is 2,5-dioxopyrrolidin-1-yl, 1,3-dioxo-3a,4,7,7a-tetrahydro-1H-isoindol-2(3H)-yl, 1,3-dioxohexahydro-1H-isoindol-2(3H)-yl, or 3,5-dioxo-4-azatricyclo[5.2.1.02.6]dec-8-en-4-yl, R2 is hydrogen, ClCO— or Cl3COCO—, and R3 is C1-6 alkyl or heterocyclyl, or forms a 3- to 7-membered heterocyclic ring together with the adjacent —O—NH—. R3 may be modified with 0 to 5 R4, and R4 may be consecutively substituted. R4 is C1-6 alkyl, C1-6 alkoxy, C1-6 alkylsulfonyl, heterocyclyl, heterocyclylcarbonyl, R5(R6)N— or a protecting group. Here, R5 and R6 each independently is hydrogen or C1-6 alkyl or together form a 3- to 7-membered heterocyclic ring. Further, R3, R5 and R6 can undergo ring closure at an arbitrary position). |
