PATENT CLAIM ANALYSIS

Application Number: 15780328
Application Type: Utility
Filing Date: 2018-05
Publication Date: 2018-12
Patent Classification: ["514", "228200"]

Abstract:
The present disclosure provides for methods for preparing tricyclic PI3K inhibitor compounds in high yield and purity in aqueous solvent systems.

Claim (Index 1):
A process for preparing a compound of Formula III from a compound of Formula II in a reaction mixture according to the following reaction scheme: the process comprising:\n (i) forming a reaction mixture comprising the compound Formula II, organoboron-R 4 , the solvent system comprising at least 5 v/v % water, the base and the catalyst; \n (ii) reacting the reaction mixture at a temperature of less than 100\u00b0 C. to form a reaction product mixture comprising compound Formula III; and \n (iii) isolating the compound Formula III, a stereoisomer, geometric isomer, tautomer, or a pharmaceutically acceptable salt thereof, from the reaction product mixture, \n wherein\n the catalyst comprises palladium and the reaction mixture comprises less than 0.05 equivalents of catalyst per equivalent of compound Formula II; \n X 1  is S, O, N, NR 6 , CR 1 , C(R 1 ) 2 , or \u2014C(R 1 ) 2 O\u2014; \n X 2  is C, CR 2  or N; \n X 3  is C, CR 3  or N; \n X 4  is halogen; \n A is a 5, 6, or 7-membered carbocyclyl or heterocyclyl ring fused to X 2  and X 3 , optionally substituted with one or more R 5 , R 10  or R 15  groups; \n R 6  is H, C 1 -C 12  alkyl, C 2 -C 8  alkenyl, C 2 -C 8  alkynyl, \u2014(C 1 -C 12  alkylene)-(C 3 -C 12  carbocyclyl), \u2014(C 1 -C 12  alkylene)(\u2014C 2 -C 20  heterocyclyl), \u2014(C 1 -C 12  alkylene)-C(\u2550O)\u2014(C 2 -C 20  heterocyclyl), (C 1 -C 12  alkylene)-(C 6 -C 20  aryl), and \u2014(C 1 -C 12  alkylene)-(C 1 -C 20  heteroaryl), where alkyl, alkenyl, alkynyl, alkylene, carbocyclyl, heterocyclyl, aryl, and heteroaryl are optionally substituted with one or more groups independently selected from F, Cl, Br, I, \u2014CH 3 , \u2014CH 2 CH 3 , \u2014C(CH 3 ) 3 , \u2014CH 2 OH, \u2014CH 2 CH 2 OH, \u2014(CH 3 ) 2 OH, \u2014CH 2 OCH 3 , \u2014CN, \u2014CO 2 H, \u2014COCH 3 , \u2014COC(CH 3 ) 3 , \u2014CO 2 CH 3 , \u2014CONH 2 , \u2014CONHCH 3 , \u2014CON(CH 3 ) 2 , \u2014C(CH 3 ) 2 CONH 2 , \u2014NO 2 , \u2014NH 2 , \u2014NHCH 3 , \u2014N(CH 3 ) 2 , \u2014NHCOCH 3 , \u2014NHS(O) 2 CH 3 , \u2014N(CH 3 )C(CH 3 ) 2 CONH 2 , \u2014N(CH 3 )CH 2 CH 2 S(O) 2 CH 3 , \u2550O, \u2014OH, \u2014OCH 3 , \u2014S(O) 2 N(CH 3 ) 2 , \u2014SCH 3 , \u2014S(O) 2 CH 3 , cyclopropyl, cyclobutyl, oxetanyl, morpholino, and 1,1-dioxo-thiopyran-4-yl; \n R 1 , R 2 , and R 3  are independently selected from H, F, Cl, Br, I, \u2014CH 3 , \u2014CH 2 CH 3 , \u2014C(CH 3 ) 3 , \u2014CH 2 OH, \u2014CH 2 CH 2 OH, \u2014C(CH 3 ) 2 OH, \u2014CH 2 OCH 3 , \u2014CN, \u2014CF3, \u2014CO 2 H, \u2014COCH 3 , \u2014COC(CH 3 ) 3 , \u2014CO 2 CH 3 , \u2014CONH 2 , \u2014CONHCH 3 , \u2014CON(CH 3 ) 2 , \u2014C(CH 3 ) 2 , \u2014CONH 2 , \u2014NO 2 , \u2014NH 2 , \u2014NHCH 3 , \u2014N(CH 3 ) 2 , \u2014NHCOCH 3 , \u2014NHS(O) 2 CH 3 , \u2014N(CH 3 )C(CH 3 ) 2 CONH 2 , \u2014N(CH 3 )CH 2 CH 2 S(O) 2 CH 3 , \u2550O, \u2014OH, \u2014OCH 3 , \u2014S(O) 2 N(CH 3 ) 2 , \u2014SCH 3 , \u2014S(O) 2 CH 3 , cyclopropyl, cyclobutyl, oxetanyl, morpholino, and 1,1-dioxo-thiopyran-4-yl; \n R 4  is selected from C 6 -C 20  aryl, C 2 -C 20  heterocyclyl and C 1 -C 20  heteroaryl, each of which are optionally substituted with one or more groups independently selected from F, CI, Br, I, \u2014CH 3 , \u2014CH 2 CH 3 , \u2014CH(CH 3 ) 2 , \u2014CH 2 CH(CH 3 ) 2 , \u2014CH 2 CH 3 , \u2014CH 2 CN, \u2014CN, \u2014CF 3 , \u2014CH 2 OH, \u2014CO 2 H, \u2014CONH 2 , CONH(CH 3 ), \u2014CON(CH 3 ) 2 , \u2014NO 2 , \u2014NH 2 , \u2014NHCH 3 , \u2014NHCOCH 3 , \u2014OH, \u2014OCH 3 , \u2014OCH 2 CH 3 , \u2014OCH(CH 3 ) 2 , \u2014SH, \u2014NHC(O)NHCH 3 , \u2014NHC(O)NHCH 2 CH 3 , \u2014NHS(O) 2 CH 3 , \u2014N(CH 3 )C(O)OC(CH 3 ) 3 , \u2014S(O) 2 CH 3 , benzyl, benzyloxy, morpholinyl, morpholinomethyl, and 4-methylpiperazin-1-yl; \n Each R 5 , R 10  and R 15  is independently selected from C 1 -C 12  alkyl, C 2 -C 8  alkenyl, C 2 -C 8  alkynyl, \u2014(C 1 -C 12  alkylene)-(C 3 -C 12  carbocyclyl), \u2014(C 1 -C 12  alkylene)-(C 2 -C 20  heterocyclyl), \u2014(C 1 -C 12  alkylene)-C(O)\u2014(C 2 -C 20  heterocyclyl), \u2014(C 1 -C 12  alkylene)-(C 6 -C 20  aryl), and \u2014(C 1 -C 12  alkylene)-(C 1 -C 20  heteroaryl); or two geminal R 5 , R 10  and/or R 15  groups form a 3, 4, 5, or 6-membered carbocyclyl or heterocyclyl ring, where alkyl, alkenyl, alkynyl, alkylene, carbocyclyl, heterocyclyl, aryl, and heteroaryl are optionally substituted with one or more groups independently selected from F, Cl, Br, I, \u2014CH 3 , \u2014CH 2 CH 3 , \u2014C(CH 3 ) 3 , \u2014CH 2 OH, \u2014CH 2 CH 2 OH, \u2014C(CH 3 ) 2 OH, \u2014CH 2 OCH 3 , \u2014CN, \u2014CH 2 F, \u2014CHF 2 , \u2014CF 3 , \u2014CO 2 H, \u2014COCH 3 , \u2014COC(CH 3 ) 3 , \u2014CO 2 CH 3 , \u2014CONH 2 , \u2014CONHCH 3 , \u2014CON(CH 3 ) 2 , \u2014C(CH 3 ) 2 CONH 2 , \u2014NO 2 , \u2014NH 2 , \u2014NHCH 3 , \u2014N(CH 3 ) 2 , \u2014NH\u2014COCH 3 , \u2014NHS(O) 2 CH 3 , \u2014N(CH 3 )C(CH 3 ) 2 CONH 2 , \u2014N(CH 3 )CH 2 CH 2 S(O) 2 CH 3 , \u2550O, \u2014OH, \u2014OCH 3 , \u2014S(O) 2 N(CH 3 ) 2 , \u2014SCH 3 , \u2014S(O) 2 CH 3 , cyclopropyl, cyclobutyl, oxetanyl, morpholino, and 1,1-dioxo-thiopyran-4-yl; and \n mor is selected from: \n wherein mor is optionally substituted with one or more R 7  groups independently selected from F, Cl, Br, I, \u2014CH 3 , \u2014CH 2 CH 3 , \u2014CH 2 CH 2 CH 3 , \u2014CH(CH 3 ) 2 , \u2014C(CH 3 ) 3 , \u2014CH 2 OCH 3 , \u2014CHF 2 , \u2014CN, \u2014CF 3 , \u2014CH 2 OH, \u2014CH 2 OCH 3 , \u2014CH 2 CH 2 OH, \u2014CH 2 C(CH 3 ) 2 OH, \u2014CH(CH 3 )OH, \u2014CH(CH 2 CH 3 )OH, \u2014CH 2 CH(OH)CH 3 , \u2014C(CH 3 ) 2 OH, \u2014C(CH 3 ) 2 OCH 3 , \u2014CH(CH 3 )F, \u2014C(CH 3 )F 2 , \u2014CH(CH 2 CH 3 )F, \u2014C(CH 2 CH 3 ) 2 F, \u2014CO 2 H, \u2014CONH 2 , \u2014CON(CH 2 CH 3 ) 2 , \u2014COCH 3 , \u2014CON(CH 3 ) 2 , \u2014NO 2 , \u2014NH 2 , \u2014NHCH 3 , \u2014N(CH 3 ) 2 , \u2014NHCH 2 CH 3 , \u2014NHCH(CH 3 ) 2 , \u2014NHCH 2 CH 2 OH, \u2014NHCH 2 CH 2 OCH 3 , \u2014NHCOCH 3 , \u2014NHCOCH 2 CH 3 , \u2014NHCOCH 2 OH, \u2014NHS(O) 2 CH 3 , \u2014N(CH 3 )S(O) 2 CH 3 , \u2550O, \u2014OH, \u2014OCH 3 , \u2014OCH 2 CH 3 , \u2014OCH(CH 3 ) 2 , \u2014SH, \u2014NHC(O)NHCH 3 , \u2014NHC(O)NHCH 2 CH 3 , \u2014S(O)CH 3 , \u2014S(O)CH 2 CH 3 , \u2014S(O) 2 CH 3 , \u2014S(O) 2 NH 2 , \u2014S(O) 2 NHCH 3 , \u2014S(O) 2 N(CH 3 ) 2 , and \u2014CH 2 S(O) 2 CH 3 .

Metadata:
- Claim Count in Document: 22.0
- Percentile: 93.0
- Lexical Diversity: 1.1
- Patent Class: 514.0
- Transitional Phrase Type: open
- Component Type: 1
- Foreign Priority: False
- Related Applications: ['14524204', '14972333', '13018068', '12586241', '14930929']

Analysis Scores:
- 35 USC 101 Eligibility (BERT): 0.7960282687083905
- 35 USC 102 Novelty (BERT): 0.5194370927254809
- Combined Prediction Score: 0.7683691511100995
- Mean Citation Score: 302.856558
- Max Citation Score: 309.51782000000014
- Similarity Product: 193.7934990437305

Labels:
- Claim Label 101: 1
- Claim Label 102: 1
- Claim Label 103: 0
- Claim Label 112: 1
- Combined Label: 1
- Label 101 Adjusted: 1

Dataset: test