# US 7,745,643 B2 · Methods of synthesizing cyclic nitro compounds

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- Number: US 7,745,643 B2
- Document ID: US7745643B2
- Status: Granted
- Kind: B2
- Application number: 12/252,278
- Filed: 2008-10-15
- Published: 2009-04-09
- Granted: 2010-06-29
- Earliest claimed: 2005-08-12
- Assignees: Alliant Techsystems Inc.
- Inventors: Louis F. Cannizzo; Kirstin F. Warner; Robert B. Wardle; Stephen P. Velarde
- Web page: https://patentgrep.com/patent/US7745643B2

## CPC

- A61K 31/397: having four-membered rings, e.g. azetidine
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61N 5/10: X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy (A61N5/01 takes precedence)
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 205/04: having no double bonds between ring members or between ring members and non-ring members
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

The present invention provides cyclic nitro compounds, pharmaceutical compositions of cyclic nitro compounds and methods of using cyclic nitro compounds and/or pharmaceutical compositions thereof to treat or prevent diseases or disorders characterized by abnormal cell proliferation, such as cancer, inflammation, cardiovascular disease and autoimmune disease.

## Claims

### Claim 1

A method of synthesizing a N-(haloacetyl)-3,3-dinitro-azetidine compound, comprising:
reacting tert-butyl-3,3-dinitroazetidine (“t-BuDNAZ”), an acid catalyst, and a haloacetyl halide.

### Claim 2 (depends on 1)

The method of claim 1, wherein reacting t-BuDNAZ, an acid catalyst, and a haloacetyl halide comprises reacting 2 molar equivalents of t-BuDNAZ, 1 molar equivalent of the haloacetyl halide, and the acid catalyst.

### Claim 3 (depends on 1)

The method of claim 1, wherein reacting t-BuDNAZ, an acid catalyst, and a haloacetyl halide comprises reacting t-BuDNAZ, the haloacetyl halide, and the acid catalyst in methylene chloride.

### Claim 4 (depends on 1)

The method of claim 1, wherein reacting t-BuDNAZ, an acid catalyst, and a haloacetyl halide comprises reacting t-BuDNAZ, boron trifluoride etherate, and bromoacetyl bromide.

### Claim 5 (depends on 4)

The method of claim 4, wherein reacting t-BuDNAZ, boron trifluoride etherate, and bromoacetyl bromide comprises producing N-(bromoacetyl)-3,3-dinitroazetidine at a yield of 75.2%.

### Claim 6 (depends on 4)

The method of claim 4, further comprising filtering, washing, and drying a reaction product of t-BuDNAZ, boron trifluoride etherate, and bromoacetyl bromide to produce N-(bromoacetyl)-3,3-dinitroazetidine.

### Claim 7 (depends on 6)

The method of claim 6, further comprising reacting the N-(bromoacetyl)-3,3-dinitroazetidine, sodium iodide, and a base.

### Claim 8 (depends on 7)

The method of claim 7, further comprising filtering, washing, and drying a reaction product of N-(bromoacetyl)-3,3-dinitroazetidine, sodium iodide, and the base to produce N-(iodoacetyl)-3,3-dinitroazetidine.

### Claim 9 (depends on 6)

The method of claim 6, further comprising reacting the N-(bromoacetyl)-3,3-dinitroazetidine, sodium azide, and a base.

### Claim 10 (depends on 9)

The method of claim 9, further comprising filtering, washing, and drying a reaction product of N-(bromoacetyl)-3,3-dinitroazetidine, sodium azide, and the base to produce N-(azidoacetyl)-3,3-dinitroazetidine.

### Claim 11 (depends on 1)

The method of claim 1, wherein reacting t-BuDNAZ, an acid catalyst, and a haloacetyl halide comprises reacting t-BuDNAZ, boron trifluoride etherate, and chloroacetyl chloride.

### Claim 12 (depends on 11)

The method of claim 11, wherein reacting t-BuDNAZ, boron trifluoride etherate, and chloroacetyl chloride comprises producing N-(chloroacetyl)-3,3-dinitroazetidine at a yield of 60%.

### Claim 13 (depends on 11)

The method of claim 11, further comprising filtering, washing, and drying a reaction product of t-BuDNAZ, boron trifluoride etherate, and chloroacetyl chloride to produce N-(chloroacetyl)-3,3-dinitroazetidine.

### Claim 14

A method of synthesizing a N-(haloacetyl)-3,3-dinitroazetidine compound, comprising:
reacting tert-butyl-3,3-dinitroazetidine (“t-BuDNAZ”), an acid catalyst, and a haloacetyl halide selected from the group consisting of bromoacetyl bromide and chloroacetyl chloride.