133627-47-1

Basic information

• Product Name: 3-PyridineCarboxamide,Nevirapine
• Synonyms: 3-PyridineCarboxamide,Nevirapine;N-(2-Lhioro-4-Methyi-J-Pyndinyl)-2-(Cyclopropyi Amino)-3-Pyridine Carboxamide;N-(2-Chioro-4-Methyi-3-Pyndinyl)-2-(Cyclopropyi AMino)-3-Pyridine CarboxaMide;N-(2-chloro-4-methylpyridin-3-yl)-2-(cyclopropylamino)pyridine-3-carboxamide
• CAS NO: 133627-47-1
• Molecular Formula: C₁₅H₁₅ClN₄O
• Molecular Weight: 302.7588
• Mol File: 133627-47-1.mol

Chemical Properties

• Melting Point: 127-129 °C
• Boiling Point: 428.9±45.0 °C(Predicted)
• Appearance: /
• Density: 1.429±0.06 g/cm3(Predicted)
• Storage Temp.: Keep in dark place,Inert atmosphere,Room temperature
• PKA: 11.17±0.70(Predicted)
• CAS DataBase Reference: 3-PyridineCarboxamide,Nevirapine(CAS DataBase Reference)
• NIST Chemistry Reference: 3-PyridineCarboxamide,Nevirapine(133627-47-1)
• EPA Substance Registry System: 3-PyridineCarboxamide,Nevirapine(133627-47-1)

Safety Data

• Hazardous Substances Data: 133627-47-1(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
3-PyridineCarboxamide,Nevirapine is used as a synthetic intermediate for the development of antiviral and antiretroviral drugs, specifically for the production of Nevirapine. It plays a crucial role in the synthesis process, contributing to the overall effectiveness of the final drug product.
As an impurity in Nevirapine:
3-PyridineCarboxamide,Nevirapine is also recognized as an impurity in Nevirapine (N391275). It is essential to monitor and control the levels of this impurity during the manufacturing process to ensure the safety, efficacy, and quality of the final drug product. The presence of impurities can affect the drug's performance and may lead to potential side effects or reduced therapeutic outcomes.

Upstream product

• 133627-46-0 2-chloro-N-(2-chloro-4-methyl-3-pyridinyl)-3-pyridinecarboxamide 
• 765-30-0 Cyclopropylamine 
• 49609-84-9 2-Chloronicotinoyl chloride 
• 2942-59-8 2-chloronicotinic acid 
• 23056-39-5 2-chloro-3-nitro-4-methylpyridine 
• 133627-45-9 3-Amino-2-chloro-4-methylpyridine 
• 639807-18-4 2-(cyclopropylamino)pyridine-3-carboxylic acid 
• 65169-38-2 2-chloro-4-methyl-3-pyridinecarbonitrile 
• 152362-01-1 2-chloro-4-methyl-3-pyridinecarboxamide 
• 6602-54-6 2-chloro-3-pyridinecarbonitrile 
• 52583-90-1 2-cyclopropylaminonicotinonitrile 
• 71493-72-6 2-(4-(dimethylamino)but-3-en-2-ylidene)malononitrile 
• 111-96-6 diethylene glycol dimethyl ether 
• 13166-10-4 isopropylidenemalonodinitrile 

Downstream Products

• 129618-40-2 Nevirapine 

Relevant articles and documents

Increasing global access to the high-volume HIV drug nevirapine through process intensification

Access to affordable medications continues to be one of the most pressing issues for the treatment of disease in developing countries. For many drugs, synthesis of the active pharmaceutical ingredient (API) represents the most financially important and technically demanding element of pharmaceutical operations. Furthermore, the environmental impact of API processing has been well documented and is an area of continuing interest in green chemical operations. To improve drug access and affordability, we have developed a series of core principles that can be applied to a specific API, yielding dramatic improvements in chemical efficiency. We applied these principles to nevirapine, the first non-nucleoside reverse transcriptase inhibitor used in the treatment of HIV. The resulting ultra-efficient (91% isolated yield) and highly-consolidated (4 unit operations) route has been successfully developed and implemented through partnerships with philanthropic entities, increasing access to this essential medication. We anticipate an even broader global health impact when applying this model to other active ingredients.

LOWCOST, HIGH YIELD SYNTHESIS OF NEVIRAPINE

Improved methods of producing the HIV drug substance, nevirapine are provided. The methods employ a cost effective and high yield synthetic methods for preparing the nevirapine building block 2-chloro-3-amino-4-picoline (CAPIC) and 2-cyclopropyl amino nicotinate (Me-CAN), and improvements in other steps of nevirapine synthesis.

Process for preparing Nevirapine

An improved process for preparing 11-cyclopropyl-5,11-dihydro-4-methyl-6H-dipyrido[3,2-b:2′,3′-e][1,4]diazepin-6-one of Formula (I).

PREPARATION AND UTILITY OF NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS

Disclosed herein are non-nucleoside reverse transcriptase inhibitors having structural Formula ( I ), processes of preparation thereof, pharmaceutical compositions thereof, and the methods of their use thereof. Formula ( I )

AN IMPROVED PROCESS FOR PREPARING NEVIRAPINE

An improved process for preparing 11-cyclopropyl-5,11-dihydro-4-methyl-6H-dipyrido [3,2-b:2',3'-e][1,4] diazepin-6-one of Formula (I).

AN IMPROVED PROCESS FOR INDUSTRIAL MANUFACTURE OF NEVIRAPINE

An improved cost-effective, environmental friendly, industrial method for manufacture of Nevirapine.Formula (I):

Method for making nevirapine

A process for making nevirapine, comprising the following steps: (a) reacting a 2-halo-3-pyridinecarbonitrile of the formula ?wherein X is a fluorine, chlorine, bromine or iodine atom, preferably chlorine or bromine, with cyclopropylamine, to yield 2-(cyclopropylamino)-3-pyridinecarbonitrile; (b) hydrolyzing the 2-(cyclopropylamino)-3-pyridinecarbonitrile to yield 2-(cyclopropylamino)-3-pyridine carboxylic acid; (c) isolating the 2-(cyclopropylamino)-3-pyridine carboxylic acid from the reaction medium; (e) treating the 2-(cyclopropylamino)-3-pyridine carboxylic acid with a chlorinating agent, to yield 2-(cyclopropylamino)-3-pyridinecarbonyl chloride; (f) reacting the 2-(cyclopropylamino)-3-pyridine carbonyl chloride with a 2-halo-4-methyl-3-pyridinamine of the formula ?wherein X is a fluorine, chlorine, bromine or iodine atom, preferably chlorine or bromine, to produce an N-(2-halo-4-methyl-3-pyridinyl)-2-(cyclopropylamino)-3-pyridinecarboxamide; and (g) cyclizing the N-(2-halo-4-methyl-3-pyridinyl)-2-(cyclopropylamino)-3-pyridinecarboxamide by treatment with a strong base, to yield nevirapine.

Novel Non-Nucleoside Inhibitors of HIV-1 Reverse Transcriptase. 1. Tricyclic Pyridobenzo- and Dipyridodiazepinones

Novel pyridobenzodiazepinones (I), pyridobenzodiazepinones (II), and dipyridodiazepinones (III) were found to inhibit human immunodeficiency virus type 1 (HIV-1) reverse transcriptase in vitro at concentrations as low as 35 nM.In all three series, small substituents (e.g., methyl, ethyl, acetyl) are preferred at the lactam nitrogen, whereas slightly larger alkyl moieties (e.g., ethyl, cyclopropyl) are favored at the other (N-11) diazepinone nitrogen.In general, lipophilic substituents are preferred on the A ring, whereassubstitution on the C ring generally reduces potency relative to the corresponding compounds with no substituents on the aromatic rings.Maximum potency is achieved with methyl substitution at the position ortho to the lactam nitrogen atom; however, in this case an unsubstituted lactam nitrogen is preferred.Additional substituents on the A ring can be readily tolerated.The dipyridodiazepinone derivative 11-cyclopropyl-5,11-dihydro-4-methyl-6H-dipyridodiazepin-6-one (96, nevirapine) is a potent (IC50 = 84 nM) and selective non-nucleoside inhibitor of HIV-1 reverse transcriptase, and has been chosen for clinical evaluation.