PATENT CLAIM ANALYSIS

Application Number: 16094707
Application Type: Utility
Filing Date: 2018-10
Publication Date: 2019-04
Patent Classification: ["585", "419000"]

Abstract:
A class of mono-protected 3-amino-2-hydroxypyridine (MPAHP) ligands that enable the meta-C—H arylation of anilines, phenols, phenylacetic acids, and biologically relevant heterocyclic compounds using norbornene as a transient mediator is disclosed. The applicability of this meta-arylation methodology in the pharmaceutical industry is illustrated for heteroaryl substrates and heteroaryl iodide coupling partners, a feat made possible by using the MPAHP ligand. The enabling nature of MPAHP ligands to achieve other meta-C—H functionalization processes is also illustrated by the development of a meta-C—H amination reaction and a meta-C—H alkynylation reaction.

Claim (Index 1):
A method of forming a reaction product containing carbon-to-carbon (C\u2014C) bond to an aryl or heteroaryl substituent at a position meta to a substituent previously present on the ring of an aromatic reactive substrate compound comprising the steps of\n a) heating a reaction mixture to a temperature of about 70\u00b0 to about 120\u00b0 C., said reaction mixture containing i) said aromatic reactive substrate compound of Formula I dissolved or dispersed in a non-aqueous solvent having a boiling point at 1 atmosphere of about 40\u00b0 to about 200\u00b0 C., that further contains dissolved or dispersed therein ii) a catalytic amount of a Pd(II) catalyst, iii) a ligand of Formula III is present at about 10 to about 50 mole percent based on the moles of reactive substrate, iv) an ethylenically unsaturated bicyclic compound of Formula II as a transient mediator present in excess over the amount of reactive substrate, v) about 1.5 to about 5 equivalents of an oxidant based on the amount of said reactive substrate, and vi) about 1.1 to about 10 equivalents of a iodo-substituted aryl or heteroaryl coupling agent (Ar\u2014I); and b) maintaining said temperature for a time period sufficient to carry out the C\u2014C bond formation at a position meta to said substituent and form a reaction product whose structural formula is shown in Formula IA wherein said iodo-substituted aryl or heteroaryl coupling agent being additionally unsubstituted,\n or said iodo-substituted aryl coupling agent being further substituted at the meta and para positions with one or two substituents independently selected from the group consisting of halogen (fluoro, chloro, bromo or iodo), C 1 -C 7 -hydrocarbyl that is straight, branched or cyclic, C 1 -C 7 -hydrocarbyloxy (C 1 -C 7 \u2014O\u2014), C 1 -C 7 -hydrocarbylthioxy (C 1 -C 7 \u2014S\u2014), cyano, nitro, perfluoro-C 1 -C 3 -hydrocarbyl, carboxy C 1 -C 7 -hydrocarbyl, C 1 -C 7 -hydrocarboyl (acyl), protected hydroxyl, protected hydroxyl-substituted C 1 -C 7 -hydrocarbyl that is straight, branched or cyclic, di-(C 1 -C 7 -hydrocarbyl) C 1 -C 7 -hydrocarbylphosphonate, protected amino wherein the protecting group(s) contains up to 10 carbon atoms and the amine nitrogen has no reactive hydrogen, and a fused ring that includes 3 or 4 added ring atoms, and at the ortho position by a carboxy C 1 -C 7 -hydrocarbyl or NH\u2014C 1 -C 7 -hydrocarboyl group; \n or said iodo-substituted heteroaryl coupling agent being further substituted with one or two substituents independently selected from the group consisting of halogen other than iodo, C 1 -C 7 -hydrocarbyl that is straight, branched or cyclic, C 1 -C 7 -hydrocarbyloxy (C 1 -C 7 \u2014O\u2014), C 1 -C 7 -hydrocarbylthioxy (C 1 -C 7 \u2014S\u2014), perfluoro-C 1 -C 3 -hydrocarbyl, carboxy C 1 -C 7 -hydrocarbyl, C 1 -C 7 -hydrocarboyl (acyl), a fused ring that includes 3 or 4 added ring atoms and in which any nitrogen atom present is free of reactive hydrogens; \n said aromatic reactive substrate compound has a structural formula shown in Formula I, below: wherein, Ring A is a heteroaromatic or carbocyclic aromatic ring structure in which the bond shown to X is at the 1-position of the ring and the substituent bonded at the 1-position constitutes the substituent previously present on the ring, the ring position rotated clock-wise from the 1-position is the ortho-position at which a hydrogen (H) is bonded, and the next position clock-wise from the ortho-position at which another hydrogen (H) is bonded is the meta-position and is the position at which the new C\u2014C bond is formed, said Ring A containing a single ring or two fused rings having a total of 5 to 10 ring atoms and in which the ring bonded to X is aromatic and any other ring fused to that aromatic ring is independently aromatic or aliphatic, and in which a heteroaromatic ring structure contains one, two or three heteroatoms that can independently be nitrogen, oxygen or sulfur atoms, said Ring A optionally further containing 1, 2 or 3 substituents other than hydrido (H) bonded to the ring atoms, which substituents are selected from the group consisting of halo other than iodo (fluoro, chloro or bromo), C 1 -C 7 -hydrocarbyl that is straight, branched or includes a 4- to 6-membered ring bonded to a straight or branched chain, C 1 -C 7 -hydrocarbyloxy (C 1 -C 7 \u2014O\u2014), C 1 -C 7 -hydrocarbylthioxy (C 1 -C 7 \u2014S\u2014), C 1 -C 2 -hydrocarbyldioxy, cyano, nitro, perfluoro-C 1 -C 3 -hydrocarbyl, carboxy C 1 -C 7 -hydrocarbyl, C 1 -C 7 -hydrocarboyl (acyl), protected amino wherein the protecting group(s) contains up to 10 carbon atoms, and a fused ring; n is zero (0) or one, such that the methylene group Y within the brackets is absent when n is zero, and present when n is one, X is O (oxygen) or NPG (a nitrogen bonded to a protecting group) when n is 1, and NPG or CH 2  (methylene) when n is zero, Ring B is a heteroaromatic single 6-membered ring or a fused 6,6- or 5,6-membered ring system containing the depicted nitrogen atom and 1 or 2 other nitrogen ring atoms, Z is carbon when n is zero or 1, and Z is nitrogen (a) when n is zero, and (b) the double bond depicted is absent and replaced by a double bond at the position of the dashed line, said Ring B optionally further containing 1, 2 or 3 substituents other than hydrido (H) bonded to the ring atoms, which substituents are selected from the group consisting of C 1 -C 7 -hydrocarbyl that is straight, branched or includes a 4- to 6-membered ring bonded to a straight or branched chain C 1 -C 3 -substituent, C 1 -C 7 -hydrocarbyloxy, trifluoromethyl-C 1 -C 3 -hydrocarbyl, trifluoromethyl-C 1 -C 3 -hydrocarbyloxy, and a fused ring; said transient mediator is an ethylenically unsaturated bicyclic compound of Formula II wherein A is CH 2 , C\u2550O or O, each of R 5 , R 6 , R 7 , R 8 , R 9 , and R 10  is independently H, C 1 -C 6 -hydrocarbyl, C 1 -C 6 -hydrocarbyloxy, C 1 -C 6 -hydrocarbyl carboxylate, C 1 -C 6 -hydrocarboyl, one or both of R 5  plus R 6  and R 7  plus R 8  together with the carbon atom to which they are bonded form one or two carbonyl groups, or one each of R 5  and R 6 , or R 7  and R 8  together with the atoms to which they are bonded form a further 4- to 6-membered aliphatic or aromatic ring that itself can be independently substituted with one or two substituent groups selected from the group consisting of a C 1 -C 6 -hydrocarbyl, a C 1 -C 6 -hydrocarbyloxy, a C 1 -C 6 -hydrocarbyl carboxylate and a nitro group; and said ligand having the structure of Formula III wherein R 15  is an acyl group containing 2 to about 12 carbon atoms or a perfluorinated acyl group containing 2 to about 6 carbon atoms, R 16  is hydrido or C 1 -C 6 -hydrocarbyl, R 17  is hydrido, C 1 -C 6 -hydrocarbyl or trifluoromethyl, R 18  is hydrido or C 1 -C 6 -hydrocarbyl, or R 16  and R 17  or R 17  and R 18  together with the carbon atoms to which they are bonded form a 6-membered ring with the depicted pyridine ring, m and p are the same and are zero or 1, such that when m and p are zero, the bracketed carbon atoms are absent and the NHR 15  group is bonded directly to the depicted pyridine ring, and when m and p are both one, R 19  and R 20  together with the carbons to which they are bonded form a phenyl ring.

Metadata:
- Claim Count in Document: 44.0
- Percentile: 97.0
- Lexical Diversity: 1.47692
- Patent Class: 585.0
- Transitional Phrase Type: open
- Component Type: 1
- Foreign Priority: False
- Related Applications: ['15547014', '14648624', '14770002', '13833976', '12719624']

Analysis Scores:
- 35 USC 101 Eligibility (BERT): 0.6714632660922278
- 35 USC 102 Novelty (BERT): 0.5777758996134814
- Combined Prediction Score: 0.6620945294443532
- Mean Citation Score: 353.11749999999995
- Max Citation Score: 471.93164
- Similarity Product: 389.2460730294609

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

Dataset: test