IP Library › Granted Patent US 12,442,027
Granted Patent B2
US 12,442,027 · App. 17/309,727 · Granted Oct 14, 2025

Method of reducing aromatic nitro compounds

Inventors: Serena Bisagni (Cambridge, GB); Amin Bornadel (Cambridge, GB); Beatriz Dominguez (Cambridge, GB); Jacques Lepaih (Cambridge, GB); Steven M. Mennen (Thousand Oaks, CA); Ahir Pushpanath (Cambridge, GB); Iustina Slabu (Cambridge, GB); Jason Tedrow (Thousand Oaks, CA); Simon J. Hedley (Thousand Oaks, CA)
Assignee: Amgen Inc.
C12P17/12C07D213/73C07D295/205
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Quick Facts
Patent No.
US 12,442,027
App. No.
17/309,727
Granted
Oct 14, 2025
Kind
B2
Abstract

A method for reducing a substrate selected from 2-methyl-5-nitropyridine and methyl 4-(2-fluoro-3-nitrobenzyl)piperazine-1-carboxylate is provided catalysed by a nitroreductase and a disproportionation agent.

Claims (20)

1. A method of reducing an aromatic nitro compound comprising the step of:

(i) contacting an aromatic nitro compound with a catalyst at ambient temperature and pressure,

wherein, the catalyst comprises:

(a) a disproportionation agent; and

(b) a nitroreductase comprising the amino acid sequence of SEQ ID NO:1 [NR-4], SEQ ID NO:2 [NR-14], SEQ ID NO:3 [NR-17] or SEQ ID NO: 6 [NR-24], and

wherein the aromatic nitro compound is 2-methyl-5-nitropyridine and the conversion of the aromatic nitro compound is greater than 90%.

2. The method of claim 1 , wherein the disproportionation agent comprises a metal selected from groups 3 to 13 of the periodic table.

3. The method of claim 1 , wherein the disproportionation agent comprises a transition metal selected from groups 5 to 11 of the periodic table.

4. The method of claim 1 , wherein the disproportionation agent comprises a transition metal selected from vanadium, chromium, molybdenum, iron, cobalt, nickel or copper.

5. The method of claim 1 , wherein the disproportionation agent is selected from CuCl 2 , Cu(OAc) 2 , Cu 2 O, Cu(0) (copper metal), FeCl 2 , FeCl 3 , Fe(acac) 3 , FeCl 2 , FeSO 4 , Fe(0) (iron metal), NaMoO 4 , NH 4 VO 3 , VOSO 4 , V(acac) 3 , V 2 O 5 , V(0) (vanadium metal) and CoCl 2 .

6. The method of claim 1 , wherein the disproportionation agent is selected from NH 4 VO 3 , VOSO 4 and V 2 O 5 .

7. The method of claim 1 , wherein the method is a method of reducing 2-methyl-5-nitropyridine to produce N-(6-methylpyridin-3-yl) hydroxylamine.

8. The method of claim 1 , wherein the method is a method of reducing 2-methyl-5-nitropyridine to produce 3-amino-6-methylpyridine.

9. The method of claim 1 , further comprising the step of isolating the product.

10. The method of claim 1 , further comprising the step of contacting the biocatalyst with a co-substrate.

11. The method of claim 10 , wherein the co-substrate is a cofactor, and optionally further comprising the step of regenerating the cofactor using a reduced cofactor regenerating system.

12. The method of claim 1 , wherein the step of contacting the aromatic nitro compound with the catalyst comprises adding discreet portions of the aromatic nitro compound to the catalyst.

13. The method of claim 1 , wherein the step of contacting the aromatic nitro compound with the catalyst comprises continuously adding the aromatic nitro compound to the catalyst.

14. The method of claim 1 , wherein the method is performed at a temperature maintained in the range 0 to 100° C.

15. The method of claim 1 , wherein the method is performed at a pH maintained in the range 3.0 to 9.0.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 14, 2025
From: JOHNSON MATTHEY PUBLIC LIMITED COMPANY
To: AMGEN INC.
Reel/Frame 072026/0857 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 14, 2025
From: BISAGNI, SERENA; BORNADEL, AMIN; DOMINGUEZ, BEATRIZ; LEPAIH, JACQUES; PUSHPANATH, AHIR; SLABU, IUSTINA
To: JOHNSON MATTHEY PUBLIC LIMITED COMPANY
Reel/Frame 072026/0872 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 14, 2025
From: MENNEN, STEVEN M.; TEDROW, JASON; HEDLEY, SIMON J.
To: AMGEN INC.
Reel/Frame 072026/0912 →
Continuity (2)
Provisional Application 62781124 · Dec 18, 2018
Related Publication 20220042055A1 · Feb 10, 2022
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Cited By (1)
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