Process for producing diazabicyclooctane derivative and intermediate thereof

1. A process for producing a compound represented by a Formula (IV), comprising: reacting a compound represented by the following Formula (I):

with a compound R 1 OH selected from the group consisting of 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[5.2.1.0 2.6 ]dec-8-ene-3,5-dione, followed by allowing a carbonylating agent selected from the group consisting of phosgene, diphosgene and triphosgene to act on the resultant compound to obtain a compound represented by the following Formula (II):

removing a protecting group P and treating the resultant compound with a base to obtain a compound represented by the following Formula (III):

and reacting the resulting compound with a compound R 3 ONH 2 to produce a compound represented by the following Formula (IV):

in said Formulas (I), (II), (III) and (IV), OBn is benzyloxy; P is an NH protecting group capable of being removed with an acid; R 1 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[5.2.1.0 2.6 ]dec-8-en-4-yl; R 2 is hydrogen, ClCO— or Cl 3 COCO—; and R 3 is C 1-6 alkyl or a heterocyclyl, or forms a 3- to 7-membered heterocyclic ring together with the adjacent —O—NH—, R 3 is optionally modified with 1 to 5 R 4 groups, R 4 is selected from the group consisting of C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylsulfonyl, a heterocyclyl, a heterocyclylcarbonyl, R 5 (R 6 )N— and a protecting group, wherein R 4 is optionally substituted with one or more groups selected from the group consisting of C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylsulfonyl, a heterocyclyl, a heterocyclylcarbonyl, R 5 (R 6 )N— and a protecting group; wherein R 5 and R 6 each independently is hydrogen or C 1-6 alkyl or together form a 3- to 7-membered heterocyclic ring; and wherein R 3 , R 5 and R 6 optionally undergo ring closure.

2. A process for producing a compound represented by a Formula (IV), comprising: allowing a carbonylating agent selected from the group consisting of phosgene, diphosgene and triphosgene to act on a compound represented by the following Formula (II), wherein R 2 is hydrogen:

followed by removing a protecting group P, treating the resultant compound with a base and further reacting the resultant compound with a compound R 3 ONH 2 to produce a compound represented by the following Formula (IV):

in said Formulas (II) and (IV), OBn is benzyloxy; P is an NH protecting group capable of being removed with an acid; R 1 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[5.2.1.0 2.6 ]dec-8-en-4-yl; and R 3 is C 1-6 alkyl or a heterocyclyl, or forms a 3- to 7-membered heterocyclic ring together with the adjacent —O—NH—, R 3 is optionally modified with 1 to 5 R 4 groups, R 4 is selected from the group consisting of C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylsulfonyl, a heterocyclyl, a heterocyclylcarbonyl, R 5 (R 6 )N— and a protecting group, wherein R 4 is optionally substituted with one or more groups selected from the group consisting of C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylsulfonyl, a heterocyclyl, a heterocyclylcarbonyl, R 5 (R 6 )N— and a protecting group; wherein R 5 and R 6 each independently is hydrogen or C 1-6 alkyl or together form a 3- to 7-membered heterocyclic ring; and wherein R 3 , R 5 and R 6 optionally undergo ring closure.

3. The process according to claim 1 or 2 , which proceeds through a compound represented by the Formula (I) or (II), wherein P is tert-butoxycarbonyl (Boc).

4. The process according to claim 1 or 2 , which proceeds through a compound represented by the Formula (II) or (III), wherein R 1 is 2,5-dioxopyrrolidin-1-yl.

5. The process according to claim 1 or 2 , which proceeds through a compound represented by the Formula (II) or (III), wherein R 1 is 1,3-dioxo-3a,4,7,7a-tetrahydro-1 H-isoindol-2(3H)-yl.

6. The process according to claim 1 or 2 , which proceeds through a compound represented by the Formula (II) or (III), wherein R 1 is 1,3-dioxohexahydro-1 H-isoindol-2(3H)-yl.

7. The process according to claim 1 or 2 , which proceeds through a compound represented by the Formula (II) or (III), wherein R 1 is 3,5-dioxo-4-azatricyclo[5.2.1.0 2.6 ]dec-8-en-4-yl.

8. The process according to claim 1 or 2 for producing a compound represented by the Formula (IV), wherein R 3 is selected from the group consisting of

2-(tert-butoxycarbonylamino)ethyl,

2-((tert-butoxycarbonyl)(methyl)amino)ethyl,

2-((tert-butoxycarbonyl)(isopropyl)amino)ethyl,

2-(dimethylamino)ethyl,

(2S)-2-((tert-butoxycarbonyl)amino)propyl,

(2R)-2-((tert-butoxycarbonyl)amino)propyl,

3-((tert-butoxycarbonyl)amino)propyl,

(2S)-tert-butoxycarbonylazetidin-2-ylmethyl,

(2R)-tert-butoxycarbonylpyrrolidin-2-ylmethyl,

(3R)-tert-butoxycarbonylpiperidin-3-ylmethyl,

(3S)-tert-butoxycarbonylpyrrolidin-3-yl,

1-(tert-butoxycarbonyl)azetidin-3-yl,

2-(benzyloxycarbonylamino)ethyl,

2-((benzyloxycarbonyl)(methyl)amino)ethyl,

2-((benzyloxycarbonyl)(isopropyl)amino)ethyl,

2-(dimethylamino)ethyl,

(2S)-2-((benzyloxycarbonyl)amino)propyl,

(2R)-2-((benzyloxycarbonyl)amino)propyl,

3-((benzyloxycarbonyl)amino)propyl,

(2S)-benzyloxycarbonylazetidin-2-ylmethyl,

(2R)-benzyloxycarbonylpyrrolidin-2-ylmethyl,

(3R)-benzyloxycarbonylpiperidin-3-ylmethyl,

(3S)-benzyloxycarbonylpyrrolidin-3-yl and

1-(benzyloxycarbonyl)azetidin-3-yl.

9. The process according to claim 1 or 2 for producing a compound represented by the following Formula (IV-1):

wherein P 2 is tert-butoxycarbonyl (Boc) or benzyloxycarbonyl (Cbz), and OBn is benzyloxy.

10. The process according to claim 1 or 2 for producing a compound represented by the following Formula (IV-1-1):

wherein Boc is tert-butoxycarbonyl and OBn is benzyloxy.

11. A compound represented by the following Formula (III-58):

wherein OBn is benzyloxy.

12. A compound represented by the following Formula (III-59):

wherein OBn is benzyloxy.

13. A compound represented by the following Formula (III-60):

wherein OBn is benzyloxy.

14. A compound represented by the following Formula (II-30):

wherein Boc is tert-butoxycarbonyl and OBn is benzyloxy.

15. A compound represented by the following Formula (II-31):

wherein Boc is tert-butoxycarbonyl and OBn is benzyloxy.

16. A compound represented by the following Formula (II-32):

wherein Boc is tert-butoxycarbonyl and OBn is benzyloxy.

17. A compound represented by the following Formula (II-33):

wherein Boc is tert-butoxycarbonyl and OBn is benzyloxy.