33155-58-7

Usage

Uses

Used in Pharmaceutical Industry:
Tert-butyl 2-(4-bromophenyl)acetate is used as a reactant for the preparation of thiophene-containing biaryl amide derivatives. These derivatives are significant as they serve as glucagon receptor antagonists, playing a crucial role in the development of treatments for diabetes and other metabolic disorders. tert-butyl 2-(4-bromophenyl)acetate's reactivity and structural features make it a valuable building block in the synthesis of these therapeutic agents.

Upstream product

• 41841-16-1 (4-bromo-phenyl)-acetic acid methyl ester 
• 75-65-0 tert-butyl alcohol 
• 1907-33-1 lithium tert-butoxide 
• 1694-31-1 tert-butyl acetoacetate 
• 589-87-7 1,4-bromoiodobenzene 
• 5292-43-3 bromoacetic acid tert-butyl ester 
• 51656-70-3 (2-tert-butoxy-2-oxoethyl)zinc(II) bromide 
• 36805-97-7 N,N-dimethylformamide di-tert-butyl acetal 
• 1878-68-8 2-(4-bromophenyl)-acetic acid 
• 98946-18-0 tert-Butyl 2,2,2-trichloroacetimidate 
• 540-88-5 acetic acid tert-butyl ester 
• 24424-99-5 di-tert-butyl dicarbonate 

Downstream Products

• 116856-62-3 4-<(tert-buthoxycarbonyl)methyl>-β-N-phthalimidostyrene 
• 959121-82-5 butyl 4-(2-tert-butoxy-2-oxoethyl)benzoate 
• 1350707-49-1 tert-butyl (1R,2S)-1-(4-bromophenyl)-2-formyl-2-methylcyclopropanecarboxylate 
• 1350707-51-5 tert-butyl (1S,2R)-2-bromo-1-(4-bromophenyl)-2-formylcyclopropanecarboxylate 
• 1350707-53-7 tert-butyl (1S,2R)-1-(4-bromophenyl)-2-chloro-2-formylcyclopropanecarboxylate 

Relevant academic research and scientific papers

Synthesis and structural characterization of a monocarboxylic inhibitor for GRB2 SH2 domain

A monocarboxylic inhibitor was designed and synthesized to disrupt the protein–protein interaction (PPI) between GRB2 and phosphotyrosine-containing proteins. Biochemical characterizations show compound 7 binds with the Src homology 2 (SH2) domain of GRB2 and is more potent than EGFR1068 phosphopeptide 14-mer. X-ray crystallographic studies demonstrate compound 7 occupies the GRB2 binding site for phosphotyrosine-containing sequences and reveal key structural features for GRB2–inhibitor binding. This compound with a –1 formal charge offers a new direction for structural optimization to generate cell-permeable inhibitors for this key protein target of the aberrant Ras-MAPK signaling cascade.

Catalytic Asymmetric Fluorination of Copper Carbene Complexes: Preparative Advances and a Mechanistic Rationale

The Cu-catalyzed reaction of substituted α-diazoesters with fluoride gives α-fluoroesters with ee values of up to 95 %, provided that chiral indane-derived bis(oxazoline) ligands are used that carry bulky benzyl substituents at the bridge and moderately bulky isopropyl groups on their core. The apparently homogeneous solution of CsF in C6F6/hexafluoroisopropanol (HFIP) is the best reaction medium, but CsF in the biphasic mixture CH2Cl2/HFIP also provides good results. DFT studies suggest that fluoride initially attacks the Cu- rather than the C-atom of the transient donor/acceptor carbene intermediate. This unusual step is followed by 1,2-fluoride shift; for this migratory insertion to occur, the carbene must rotate about the Cu?C bond to ensure orbital overlap. The directionality of this rotatory movement within the C2-symmetric binding site determines the sense of induction. This model is in excellent accord with the absolute configuration of the resulting product as determined by X-ray diffraction using single crystals of this a priori wax-like material grown by capillary crystallization.

Three-Component Synthesis of Isoquinoline Derivatives by a Relay Catalysis with a Single Rhodium(III) Catalyst

A rhodium(III)-catalyzed one-pot three-component reaction of N-methoxybenzamide, α-diazoester, and alkyne was developed, providing an alternative way to synthesize isoquinoline derivatives. Mechanistically, it is a relay catalysis, and the reaction occurred via successive O-alkylation and C-H activation processes, both of which were promoted by the same catalyst.

Rapid Assembly of Saturated Nitrogen Heterocycles in One-Pot: Diazo-Heterocycle “Stitching” by N–H Insertion and Cyclization

Methods that provide rapid access to new heterocyclic structures in biologically relevant chemical space provide important opportunities in drug discovery. Here, a strategy is described for the preparation of 2,2-disubstituted azetidines, pyrrolidines, pi

Discovery of thiophene-containing biaryl amide derivatives as novel glucagon receptor antagonists

A novel series of thiophene-containing biaryl amide glucagon receptor (GCGR) antagonists were designed and synthesized. Two compounds of this series, 14f and 14h, exhibited good GCGR binding (IC50?=?6.1 and 4.4?μm, respectively) and cAMP functional activities (IC50?=?4.4 and 14.4?μm, respectively). The possible binding modes of compounds 14f and 14h with GCGR were explored by molecular simulation.

Copper-catalyzed coupling of aryl iodides and tert-butyl keto esters: Efficient access to α-aryl ketones and α-arylacetic acid tert-butyl esters

CuI/trans-4-hydroxy-l-proline catalyzed coupling of aryl iodides with tert-butyl keto esters proceeded smoothly at 40 °C in DMF, providing α-aryl ketones after acid-promoted deprotection and decarboxylation of tert-butyl ester group. While CuI/2-picolinic acid catalyzed coupling of aryl iodides with tert-butyl acetoacetate at 70 °C in dioxane delivered α-arylacetic acid tert-butyl esters upon spontaneous deacylation. A wide range of functional groups, such as acetyl, methoxy, nitrile, nitro, bromo, and chloro were compatible with the reaction conditions.

A chemoselective Reformatsky-Negishi approach to α-haloaryl esters

A practical synthesis of α-haloaryl esters has been achieved via a chemoselective Negishi coupling of poly-halogenated aromatics and Reformatsky reagents in the presence of catalytic Pd(dba)2 and Xantphos. This chemistry tolerates a variety of aryl halides and was successfully applied to the synthesis of Ibuprofen. The α-haloaryl ester products, exemplified by ethyl 2-(4-bromo-2-chlorophenyl)acetate (3a), can be further functionalized via palladium or copper catalysis to afford an array of α-aryl esters.

CARBAMOYL COMPOUNDS AS DGAT1 INHIBITORS 190

DGAT-1 inhibitor compounds of formula (I), pharmaceutically-acceptable salts and pro- drugs thereof are described, together with pharmaceutical compositions, processes for making them and their use in treating, for example, obesity wherein, for example, Ring A is optionally substituted 2,6-pyrazindiyl; X is =O; Ring B is optionally substituted 1,4-phenylene; Y1 is a direct bond or -O-; Y2 is -(CH 2) r- wherein r is 2 or 3; n is 0 or n is 1 when Y1 is a direct bond between Ring B and Ring C and when Ring B is 1,4-phenylene and Ring C is (4-6C)cycloalkane; Ring C is optionally substituted (4-6C)cycloalkane, (7-10C)bicycloalkane, (8-12C)tricycloalkane, phenylene or pryidindiyl; L is a direct bond or -O-; p is 0, 1 or 2 and when p is 1 or 2 RA1 and RA2 are each independently hydrogen or (1-4C)alkyl; Z is carboxy or a mimic or bioisostere thereof.

GLUCAGON RECEPTOR ANTAGONIST COMPOUNDS, COMPOSITIONS CONTAINING SUCH COMPOUNDS AND METHODS OF USE

Glucagon receptor antagonist compounds are disclosed. The compounds are useful for treating type 2 diabetes and related conditions. Pharmaceutical compositions and methods of treatment are also included.

MATRIX METALLOPROTEINASE INHIBITORS

Compounds of Formula (I), wherein R1 represents optionally substituted -C4-12 alkyl, -C2-10alkylcycloalkyl, -C2-6 alkyl heterocycloalkyl, -C2-6alkylaryl, optionally substituted 5- or 6- membered aryl or heteroaryl, except pyridinyl. Z represents a bond, CH2, O, S, SO, SO2, NR4, OCR4R5, CR4R5O, or Z, R1 and Q together form an optionally substituted fused tricyclic group; Q represents an optionally substituted 5- or 6- membered aryl or heteroaryl ring; X represents COR3; R2 represents CONH2, CO2H, CO2R7, SO2R7 or SO2NR8R9, except that R2; may not represent CO2R7 when X is CONH2 ; R3 represents OR6, or NR8R9; R4 and R5 each independently represents H, C1-6 alkyl or C1-4 alkylaryl; R6 represents H or C1-6 alkyl; R7 represents C1-6 alkyl; R8 and R9 each independently represents H or C1-6 alkyl or R8 and R9 together with the nitrogen atom to which they are attached form a 5- or 6- membered ring which may optionally include 1 or more further heteroatoms selected from O, S and N; and physiologically functional derivatives thereof with the exception of [3-(acetylamino)-4-cyclohexylphenyl]-butanedioic acid and 3-(acetylamino)-4-cyclohexylphenyl]-butanedioic acid diethyl ether; butanedioic acid [3-methoxy-4-(phenylmethoxy)phenyl]; butanedioic acid [4-(phenylmethoxy)phenyl]; with the proviso that when R1 represents C4-12 alkyl, Z is other than a bond, O or CH2; and physiologically functional derivatives thereof , processes for their preparation, pharmaceutical formulations containing them and their use as inhibitors of matrix metallproteinase enzymes (MMPs) are described.