19733-56-3

Usage

Uses

Used in Pharmaceutical Industry:
4-Piperidin-3-ylaniline is used as a reagent for the large-scale synthesis of oral PARP inhibitors. It plays a crucial role in the development of these inhibitors, which are important for their potential therapeutic applications in treating various types of cancer. Its structural properties allow it to be incorporated into the molecular framework of PARP inhibitors, contributing to their efficacy and selectivity in targeting cancer cells.

Upstream product

• 2945-08-6 methyl (4-nitrophenyl)acetate 
• 104-03-0 4-nitrobenzeneacetic acid 
• 100-00-5 4-chlorobenzonitrile 
• 19733-55-2 3-(4-nitrophenyl)piperidine 
• 92137-91-2 3-(4-nitrophenyl)piperidine-2,6-dione 
• 119023-00-6 methyl 4-cyano-4-(4-nitrophenyl)butanoate 
• 30698-33-0 methyl 2-cyano-2-(4-nitrophenyl)acetate 
• 40114-49-6 1-benzyl-3-piperidone 
• 358-23-6 trifluoromethylsulfonic anhydride 
• 171364-83-3 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)nitrobenzene 
• 586-78-7 para-nitrophenyl bromide 
• 1692-25-7 3-pyridylboronic acid 
• 4282-46-6 3-(4'-nitrophenyl)pyridine 

Downstream Products

• 1196713-22-0 (3S)-3-(4-aminophenyl)piperidinium (2R,3R)-3-carboxy-2,3-dihydroxypropanoate 
• 1171197-20-8 (3S)-3-(4-aminophenyl)piperidine-1-carboxylic acid tert-butyl ester 
• 875798-79-1 3-(4-aminophenyl)piperidine-1-carboxylic acid tert-butyl ester 
• 1038915-60-4 (3S)-3-[4-{7-(aminocarbonyl)-2H-indazol-2-yl}phenyl]piperidine 
• 1312106-32-3 18-(nitrobenzylideneamino)phenylpiperidine-1-carboxylate 
• 1038916-08-3 2-{4-[(3S)-1-(tert-butoxycarbonyl)piperidin-3-yl]phenyl}-2H-indazole-7-carboxylic acid 
• 1196713-21-9 (3S)-3-(4-aminophenyl)piperidine 
• 1038916-11-8 tert-butyl (3S)-3-{4-[7-(aminocarbonyl)-2H-indazol-2-yl]phenyl}piperidine-1-carboxylate 
• 1196713-67-3 2-[4-((3S)-(tertbutoxycarbonyl)piperidin-3-yl)phenyl]-2H-indazole-7-carboxylic acid methyl ester 
• 1263284-59-8 (+)-(R)-tert-butyl 3-(4-aminophenyl)piperidine-1-carboxylate 
• 1038915-64-8 (3S)-3-[4-[7-(aminocarbonyl)-2H-indazol-2-yl]phenyl]piperidinium chloride 

Relevant academic research and scientific papers

PROCESSES FOR THE PREPARATION OF NIRAPARIB AND INTERMEDIATES THEREOF

The present invention relates to novel procedures and novel intermediates useful in the synthesis of Niraparib or any salt thereof.

Method for preparing Niraparib of PARP (poly-ADP-ribose polymerase) inhibitor

The invention discloses a method for preparing 2-(4-((3S)-3-piperidyl) phenyl)-2H-indazole-7-formamide of a compound. Benzyl protected-piperidone is generated into piperidone of 3-triflic anhydride under the action of triflic anhydride, the piperidone and nitrobenzoic acid are subjected to Suzuki reaction to obtain a coupled product, 3-(4-aminophenyl) piperidine is obtained under the action of a palladium reagent, (S)-3-(4-halogenated phenyl) piperidine is prepared with a chirality resolution reagent, the (S)-3-(4-halogenated phenyl) piperidine is condensed with 3-formyl-2-methyl nitrobenzoate to form pyrazolone ring under the action of sodium azide, and the Niraparid (with the molecular entity of 2-(4-((3S)-3-piperidyl) phenyl)-2H-indazole-7-formamide) is prepared via aminolysis.

Preparation method of 4-(3-piperidino) aniline and tartrate thereof

The invention belongs to the field of organic synthesis and particularly relates to a preparation method of 4-(3-piperidino) aniline and tartrate thereof. The preparation method is characterized by comprising the following steps: taking p-nitrophenylaceti

Method for preparing 4-(piperidine-3-yl)aniline

The invention discloses a method for preparing 4-(piperidine-3-yl)aniline. The method is characterized by comprising the steps that a salifying reaction is carried out, wherein 3-(4-nitrophenyl)pyridine and 3-halogenated propylene react to obtain N-allyl-3-(4-nitrophenyl)pyridine quaternary ammonium salt; a reduction reaction is carried out, wherein N-allyl-3-(4-nitrophenyl)pyridine quaternary ammonium salt is mixed with zinc chloride, and then sodium borohydride is added for reduction to obtain 4-(piperidine-3-yl)aniline. According to the method, use of precious metal is avoided, production cost of the intermediate 4-(piperidine-3-yl)aniline is greatly lowered, conditions are mild, nitryl and a pyridine ring are subjected to reduction at a time, a good yield is obtained, and the method is especially suitable for large-scale industrial production.

Preparation method of niraparib intermediate 4-(piperidyl-3-yl)aniline

The invention belongs to the field of medicine synthesis, and relates to a preparation method of niraparib intermediate 4-(piperidyl-3-yl)aniline. According to the method, halogenated 1-benzyl-3-(4-nitrophenyl)pyridinium used as the initial raw material is subjected to catalytic hydrogenation in the presence of Pd/C to obtain the 4-(piperidyl-3-yl)aniline. The method has the advantages of low cost, high yield, high safety and environment friendliness, can effectively avoid the generation of the N-(4-(pyridyl-3-yl)phenyl)hydroxylamine impurity, is easy to operate and suitable for large-scale production, and provides technical supports for further preparation of high-purity niraparib.

A prepares Nepal to pull handkerchief Nepal method (by machine translation)

The invention discloses a compound 2 - [4 - ((3S) - 3 - piperidinyl) phenyl] - 2H - indazole - 7 - carboxamide preparation method, through the 4 - nitro phenylpyridyl with reaction produced animal pen halogenphenmethyl season ammonium salt, by sodium borohydride reduction of the pyridine quaternary ammonium salt, in the palladium reagent obtained under the action of the 3 - (4 - aminophenyl) piperidine, in the chiral reagent obtained under the action of the (S)- 3 - (4 - halophenyl) piperidine, with 3 - formyl - 2 - nitro-benzoic acid methyl ester condensation and in sodium azide formed under the action of powder medicine, after preparing the amine Niraparib (molecular entity is: 2 - [4 - ((3S) - 3 - piperidinyl) phenyl] - 2H - indazole - 7 - carboxamide). (by machine translation)

Development of a fit-for-purpose large-scale synthesis of an oral PARP inhibitor

Compound (1) a poly(ADP-ribose)polymerase (PARP) inhibitor has been made by a fit-for-purpose large-scale synthesis using either a classical resolution or chiral chromatographic separation. The development and relative merits of each route are discussed,

Discovery of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (MK-4827): A novel oral poly(ADP-ribose)polymerase (PARP) inhibitor efficacious in BRCA-1 and -2 mutant tumors

We disclose the development of a novel series of 2-phenyl-2H-indazole-7- carboxamides as poly(ADP-ribose) polymerase (PARP) 1 and 2 inhibitors. This series was optimized to improve enzyme and cellular activity, and the resulting PARP inhibitors display antiproliferation activities against BRCA-1 and BRCA-2 deficient cancer cells, with high selectivity over BRCA proficient cells. Extrahepatic oxidation by CYP450 1A1 and 1A2 was identified as a metabolic concern, and strategies to improve pharmacokinetic properties are reported. These efforts culminated in the identification of 2-{4-[(3S)-piperidin-3-yl] phenyl}-2H-indazole-7-carboxamide 56 (MK-4827), which displays good pharmacokinetic properties and is currently in phase I clinical trials. This compound displays excellent PARP 1 and 2 inhibition with IC50 = 3.8 and 2.1 nM, respectively, and in a whole cell assay, it inhibited PARP activity with EC50 = 4 nM and inhibited proliferation of cancer cells with mutant BRCA-1 and BRCA-2 with CC50 in the 10-100 nM range. Compound 56 was well tolerated in vivo and demonstrated efficacy as a single agent in a xenograft model of BRCA-1 deficient cancer.