US 12,331,023 B2
Substituted heterocyclyl derivatives as CDK inhibitors
Susanta Samajdar, Bangalore (IN); Ramulu Poddutoori, Karimnagar (IN); Chetan Pandit, Bangalore (IN); Subhendu Mukherjee, Hooghly (IN); and Rajeev Goswami, Deharadun (IN)
Assigned to Aurigene Oncology Limited, Bangalore (IN)
Filed by Aurigene Oncology Limited, Bangalore (IN)
Filed on Oct. 7, 2021, as Appl. No. 17/496,452.
Application 17/496,452 is a continuation of application No. 16/867,761, filed on May 6, 2020, granted, now 11,174,232.
Application 16/867,761 is a continuation of application No. 15/579,246, granted, now 10,689,347, previously published as PCT/IB2016/053267, filed on Jun. 3, 2016.
Claims priority of application No. 2803/CHE/2015 (IN), filed on Jun. 4, 2015; and application No. 6214/CHE/2015 (IN), filed on Nov. 18, 2015.
Prior Publication US 2022/0098156 A1, Mar. 31, 2022
Prior Publication US 2023/0250062 A9, Aug. 10, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 231/40 (2006.01); A61K 31/415 (2006.01); A61K 31/4155 (2006.01); A61K 31/416 (2006.01); A61K 31/4439 (2006.01); A61K 31/454 (2006.01); A61K 31/4545 (2006.01); A61K 31/4725 (2006.01); A61K 31/496 (2006.01); A61K 31/497 (2006.01); A61K 31/5377 (2006.01); A61K 45/06 (2006.01); C07D 231/56 (2006.01); C07D 401/04 (2006.01); C07D 401/12 (2006.01); C07D 401/14 (2006.01); C07D 403/12 (2006.01); C07D 413/12 (2006.01); C07D 471/04 (2006.01)
CPC C07D 231/40 (2013.01) [A61K 31/415 (2013.01); A61K 31/4155 (2013.01); A61K 31/416 (2013.01); A61K 31/4439 (2013.01); A61K 31/454 (2013.01); A61K 31/4545 (2013.01); A61K 31/4725 (2013.01); A61K 31/496 (2013.01); A61K 31/497 (2013.01); A61K 31/5377 (2013.01); A61K 45/06 (2013.01); C07D 231/56 (2013.01); C07D 401/04 (2013.01); C07D 401/12 (2013.01); C07D 401/14 (2013.01); C07D 403/12 (2013.01); C07D 413/12 (2013.01); C07D 471/04 (2013.01)] 18 Claims
 
1. A process for preparing a compound of formula (IC-1),

OG Complex Work Unit Chemistry
the process comprising the steps:
a) reacting a compound of formula (a) with a compound of formula (b) to afford a compound of formula (c):

OG Complex Work Unit Chemistry
b) reacting the compound of formula (c) with 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (g) to afford a compound of formula (h):

OG Complex Work Unit Chemistry
 and
c) coupling the compound of formula (h) with a compound of formula (i) to afford a compound of formula (IC-1):

OG Complex Work Unit Chemistry
wherein,
ring A is 1,3-phenylene;
ring B is phenyl, piperidinyl, pyridinyl, 1,2,3-6-tetrahydropyridinyl, piperazinyl, pyrazinyl, pyrazolyl, morpholinyl, indolinyl or pyrrolidinyl;
R1 is hydrogen;
R2 is (C1-C6) alkyl or (C3-C10) cycloalkyl;
R3 is hydrogen or (C1-C6) alkyl;
R4 at each occurrence is fluoro;
R5 is

OG Complex Work Unit Chemistry
 wherein R5′ is hydrogen, halo, methoxymethyl, or —CH2NRaRb; and R5″ is H;
Ra and Rb are each independently (C1-C6) alkyl, (C1-C6) alkoxy or methyloxyethyl; alternatively, Ra and Rb together with the nitrogen atom to which they are attached form an optionally substituted 5 to 6 membered ring containing 0-2 additional heteroatoms that are independently N, O or S; wherein the 5 to 6 membered ring is optionally substituted with one or more substituents selected from halo, cyano, cyano (C1-C6) alkyl, methyloxymethyl or —COO—(C1-C6) alkyl;
R6 at each occurrence is fluoro, (C1-C6) alkyl, (C1-C6) alkoxy;
L1 is *—CRcRd—C(O)—; wherein * is the point of attachment with the phenyl ring;
Rc and Rd independently are hydrogen or (C1-C6) alkyl; alternatively, Rc and Rd together with the carbon atom to which they are attached form a (C3-C10) cycloalkyl ring;
m is 0, or 1; and
q is 0 to 2.