US 11,851,420 B2
Pyrazole derivatives
James Alan Morris, Bracknell (GB); Sally Elizabeth Russell, Bracknell (GB); and Sean Ng, Bracknell (GB)
Assigned to SYNGENTA CROP PROTECTION AG, Basel (CH)
Filed by SYNGENTA CROP PROTECTION AG, Basel (CH)
Filed on Dec. 7, 2022, as Appl. No. 18/062,744.
Application 18/062,744 is a continuation of application No. 17/108,110, filed on Dec. 1, 2020, granted, now 11,548,873.
Application 17/108,110 is a continuation of application No. 16/782,866, filed on Feb. 5, 2020, granted, now 10,882,846, issued on Jan. 5, 2021.
Claims priority of application No. 1901559 (GB), filed on Feb. 5, 2019.
Prior Publication US 2023/0114845 A1, Apr. 13, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 403/04 (2006.01); A01N 43/54 (2006.01); A01N 43/58 (2006.01); A01N 43/80 (2006.01); A01N 43/90 (2006.01); C07D 401/04 (2006.01); C07D 401/14 (2006.01); C07D 409/14 (2006.01); C07D 413/04 (2006.01); C07D 471/04 (2006.01); C07D 487/04 (2006.01); A01N 43/56 (2006.01); C07D 207/337 (2006.01); C07D 207/34 (2006.01); C07D 207/325 (2006.01)
CPC C07D 403/04 (2013.01) [A01N 43/54 (2013.01); A01N 43/56 (2013.01); A01N 43/58 (2013.01); A01N 43/80 (2013.01); A01N 43/90 (2013.01); C07D 207/325 (2013.01); C07D 207/337 (2013.01); C07D 207/34 (2013.01); C07D 401/04 (2013.01); C07D 401/14 (2013.01); C07D 409/14 (2013.01); C07D 413/04 (2013.01); C07D 471/04 (2013.01); C07D 487/04 (2013.01)] 21 Claims
 
1. A process for the manufacture of a compound of formula (G)

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wherein ring A is a di-substituted pyrazole, substituted on a ring nitrogen by RB2 and substituted on a ring carbon by RB3;
RB2 is C1-C3 alkyl or C1-C3fluoroalkyl,
RB3 is halogen, C1-C3fluoroalkyl, C1-C3haloalkoxy, C1-C3alkoxy, C1-C3haloalkyl, or C1-C3alkyl;
R2 is an aryl or heteroaryl ring optionally substituted by 1 to 3 R25; and
each R25 is independently halogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy, C1-C6haloalkoxy, cyano, nitro, C1-C6alkylthio, C1-C6alkylsulphinyl, or C1-C6alkylsulphonyl; said process comprising:
(i) reacting a compound of formula (A)

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wherein ring A, RB2 and RB3 are as defined previously, and Hal is iodo, bronco or chloro, with 1-dimethylamino-2-nitroethylene to form a compound of formula (B)

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(ii) reacting the compound of formula (B) from step (i) with a malonate in solvent, under enantioselective nickel catalysis to give a compound of formula (C)

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(iii) reacting the compound of formula (C) from step (ii) with a reducing agent in the presence of a catalyst to give a compound of formula (D)

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(iv) hydrolysing the compound of formula (D) from step (iii) in an aqueous hydroxide/ethanol mixture to give the compound of formula (E)

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(v) methylating the lactam nitrogen of the compound of formula (E) formed in step (iv) using excess base in solvent, to form a compound of formula (1′)

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(vi) coupling the compound of formula (F) from step (v) with an aniline of formula R2—NH2 wherein R2 is as defined above under standard amide coupling conditions, to yield a compound of formula (G)

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