US 12,129,237 B2
Substituted diaminocarboxamide and diaminocarbonitrile pyrimidines, compositions thereof, and methods of treatment therewith
Brydon L. Bennett, San Diego, CA (US); Mercedes Delgado, San Diego, CA (US); Jan Elsner, Solana Beach, CA (US); Paul Erdman, San Diego, CA (US); Robert Hilgraf, San Diego, CA (US); Laurie Ann LeBrun, San Diego, CA (US); Meg McCarrick, San Diego, CA (US); Mehran F. Moghaddam, Carlsbad, CA (US); Mark A. Nagy, Encinitas, CA (US); Stephen Norris, San Diego, CA (US); David A. Paisner, Portland, OR (US); William J. Romanow, San Diego, CA (US); Yoshitaka Satoh, Poway, CA (US); Marianne Sloss, San Diego, CA (US); Jayashree Tikhe, San Diego, CA (US); and Won Hyung Yoon, San Diego, CA (US)
Assigned to Signal Pharmaceuticals, LLC, San Diego, CA (US)
Filed by SIGNAL PHARMACEUTICALS, LLC, San Diego, CA (US)
Filed on Mar. 29, 2022, as Appl. No. 17/707,471.
Application 17/707,471 is a continuation of application No. 17/136,276, filed on Dec. 29, 2020, granted, now 11,325,890.
Application 17/136,276 is a continuation of application No. 16/291,193, filed on Mar. 4, 2019, granted, now 10,919,865, issued on Feb. 16, 2021.
Application 16/291,193 is a continuation of application No. 16/021,415, filed on Jun. 28, 2018, granted, now 10,266,500, issued on Apr. 23, 2019.
Application 16/021,415 is a continuation of application No. 15/616,039, filed on Jun. 7, 2017, granted, now 10,040,770, issued on Aug. 7, 2018.
Application 15/616,039 is a continuation of application No. 14/814,633, filed on Jul. 31, 2015, granted, now 9,701,643, issued on Jul. 11, 2017.
Application 14/814,633 is a continuation of application No. 13/451,574, filed on Apr. 20, 2012, granted, now 9,139,534, issued on Sep. 22, 2015.
Claims priority of provisional application 61/555,339, filed on Nov. 3, 2011.
Claims priority of provisional application 61/478,076, filed on Apr. 22, 2011.
Prior Publication US 2023/0116093 A1, Apr. 13, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 239/48 (2006.01); A61K 31/505 (2006.01); C07D 239/38 (2006.01); C07D 239/47 (2006.01); C07D 401/04 (2006.01); C07D 401/12 (2006.01); C07D 403/12 (2006.01); C07D 405/12 (2006.01); C07D 409/12 (2006.01)
CPC C07D 239/48 (2013.01) [A61K 31/505 (2013.01); C07D 239/38 (2013.01); C07D 239/47 (2013.01); C07D 401/04 (2013.01); C07D 401/12 (2013.01); C07D 403/12 (2013.01); C07D 405/12 (2013.01); C07D 409/12 (2013.01)] 6 Claims
 
1. A method for preparing a compound of formula (IIb):

OG Complex Work Unit Chemistry
the method comprising contacting a compound of formula (IIc):

OG Complex Work Unit Chemistry
with NH4Cl in the presence of a coupling agent and a base, in a solvent, wherein:
R1 is substituted or unsubstituted C1-8 alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted non-aromatic heterocyclyl, substituted or unsubstituted alkyl-(saturated or partially saturated cycloalkyl), or substituted or unsubstituted alkylheterocyclyl, provided that R1 is not 1-aminocyclohexyl;
Rx is a C1-2 alkyl; and
wherein when a C1-8 alky group is substituted, the C1-8 alkyl group is substituted with halogen, alkyl, hydroxyl, alkoxy, alkoxyalkyl, amino, alkylamino, carboxy, nitro, cyano, thiol, thioether, imine, imide, amidine, guanidine, enamine, aminocarbonyl, acylamino, phosphonato, phosphine, thiocarbonyl, sulfonyl, sulfone, sulfonamide, ketone, aldehyde, ester, urea, urethane, oxime, hydroxyl amine, alkoxyamine, aralkoxyamine, N-oxide, hydrazine, hydrazide, hydrazone, azide, isocyanate, isothiocyanate, cyanate, thiocyanate, B(OH)2, or O(alkyl)aminocarbonyl,
wherein when a group, other than a C1-8 alkyl group, is substituted, the group is substituted with halogen, alkyl, hydroxyl, alkoxy, alkoxyalkyl, amino, alkylamino, carboxy, nitro, cyano, thiol, thioether, imine, imide, amidine, guanidine, enamine, aminocarbonyl, acylamino, phosphonato, phosphine, thiocarbonyl, sulfonyl, sulfone, sulfonamide, ketone, aldehyde, ester, urea, urethane, oxime, hydroxyl amine, alkoxyamine, aralkoxyamine, N-oxide, hydrazine, hydrazide, hydrazone, azide, isocyanate, isothiocyanate, cyanate, thiocyanate, oxo, B(OH)2, O(alkyl)aminocarbonyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, aryloxy, aralkyloxy, heterocyclyloxy or heterocyclylalkoxy, and
wherein the coupling agent is selected from the group consisting of HATU, CDI, HBTU, and ethyl chloroformate, and the base is selected from the group consisting of DIEA, TEA, and potassium carbonate.