518047-40-0

Basic information

• Product Name: tert-butyl 3-cyanomorpholine-4-carboxylate
• Synonyms: tert-butyl 3-cyanomorpholine-4-carboxylate;N-Boc-3-cyanomorpholine;4-Boc-3-cyanomorpholine;3-Cyano-4-morpholinecarboxylic acid tert-butyl ester;4-Morpholinecarboxylic acid, 3-cyano-, 1,1-diMethylethyl ester;3-Cyano-Morpholine-4-carboxylicacidtert-butylester
• CAS NO: 518047-40-0
• Molecular Formula: C₁₀H₁₆N₂O₃
• Molecular Weight: 212.24564
• Mol File: 518047-40-0.mol

Chemical Properties

• Melting Point: 100-101℃
• Boiling Point: 340℃
• Flash Point: 160℃
• Appearance: /
• Density: 1.13
• Refractive Index: 1.488
• Storage Temp.: 2-8°C
• CAS DataBase Reference: tert-butyl 3-cyanomorpholine-4-carboxylate(CAS DataBase Reference)
• NIST Chemistry Reference: tert-butyl 3-cyanomorpholine-4-carboxylate(518047-40-0)
• EPA Substance Registry System: tert-butyl 3-cyanomorpholine-4-carboxylate(518047-40-0)

Safety Data

• Hazardous Substances Data: 518047-40-0(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Tert-butyl 3-cyanomorpholine-4-carboxylate is used as a reactant for the synthesis of HIV integrase inhibitors. These inhibitors play a crucial role in the treatment of HIV by blocking the integration of the viral DNA into the host's genome, thereby preventing the replication and spread of the virus. tert-butyl 3-cyanomorpholine-4-carboxylate's structural properties make it an ideal candidate for the development of potent and selective integrase inhibitors, which can be further optimized for improved efficacy and safety.

InChI:InChI=1/C10H16N2O3/c1-10(2,3)15-9(13)12-4-5-14-7-8(12)6-11/h8H,4-5,7H2,1-3H3

Upstream product

• 518047-39-7 tert-butyl 3-(aminocarbonyl)morpholine 4-carboxylate 
• 24424-99-5 di-tert-butyl dicarbonate 
• 97039-63-9 morpholine-3-carbonitrile 
• 212650-43-6 4-(tert-butoxycarbonyl)morpholine-3-carboxylic acid 
• 19158-51-1 P-toluenesulfonyl cyanide 
• 220199-85-9 morpholine-4-carboxylic acid tert-butyl ester 
• 7677-24-9 trimethylsilyl cyanide 
• 195964-53-5 tert-butyl 3-methoxymorpholine-4-carboxylate 

Downstream Products

• 66937-99-3 morpholine-3-carboxylic acid hydrochloride 
• 475106-18-4 tert‐butyl N‐[(morpholin‐3‐yl)methyl]carbamate 
• 518058-62-3 tert-butyl 3-[amino(hydroxyimino)methyl]morpholine-4-carboxylate 
• 519030-38-7 N-(4-fluorobenzyl)-5,6-dihydroxy-2-(morpholin-3-yl)pyrimidine-4-carboxamide 
• 518058-62-3 tert-butyl 3-[amino(hydroxyimino)methyl]morpholine-4-carboxylate 

Relevant articles and documents

C(sp3)?H Cyanation Promoted by Visible-Light Photoredox/Phosphate Hybrid Catalysis

Inspired by the reaction mechanism of photo-induced DNA cleavage in nature, a C(sp3)?H cyanation reaction promoted by visible-light photoredox/phosphate hybrid catalysis was developed. Phosphate radicals, generated by one-electron photooxidation of phosphate salt, functioned as a hydrogen-atom-transfer catalyst to produce nucleophilic carbon radicals from C(sp3)?H bonds with a high bond-dissociation energy. The resulting carbon radicals were trapped by a cyano radical source (TsCN) to produce the C?H cyanation products. Due to the high functional-group tolerance and versatility of the cyano group, the reaction will be useful for realizing streamlined building block syntheses and late-stage functionalization of drug-like molecules.

Synthesis of 3-oxadiazolyl/triazolyl morpholines: Novel scaffolds for drug discovery

Synthesis of isomeric 3-oxadiazolyl/triazolyl morpholines was performed based on a common intermediate on the gram scale. The target compounds were designed as novel scaffolds for the medicinal chemistry. The key reaction was an electrochemical CH-oxidati

Photoinduced direct cyanation of C(sp3)-H bonds

A general and practical synthetic protocol for the direct transformation of unreactive C(sp3)-H bonds to C(sp3)-CN bonds has been developed. The homolytic cleavage of the C-H bond is initiated by photo-excited benzophenone, and the resulting carbon radical subsequently reacts with tosyl cyanide to afford the corresponding nitrile in a highly efficient manner. The present methodology is widely applicable to various starting materials including ethers, alcohols, amine derivatives, alkanes, and alkylbenzenes. This newly developed C-H cyanation protocol provides a powerful tool for selective one-carbon elongation for the construction of architecturally complex molecules. Georg Thieme Verlag Stuttgart - New York.

Dihydroxypyrimidine-4-carboxamides as novel potent and selective HIV integrase inhibitors

Human immunodeficiency virus type-1 (HIV-1) integrase, one of the three constitutive viral enzymes required for replication, is a rational target for chemotherapeutic intervention in the treatment of AIDS that has also recently been confirmed in the clinical setting. We report here on the design and synthesis of N-benzyl-5,6-dihydroxypyrimidine-4-carboxamides as a class of agents which exhibits potent inhibition of the HIV-integrase-catalyzed strand transfer process. In the current study, structural modifications on these molecules were made in order to examine effects on HIV-integrase inhibitory potencies. One of the most interesting compounds for this series is 2-[1-(dimethylamino)-1-methylethyl]-N-(4-fluorobenzyl)-5,6-dihydroxypyrimidine- 4-carboxamide 38, with a CIC95 of 78 nM in the cell-based assay in the presence of serum proteins. The compound has favorable pharmacokinetic properties in preclinical species (rats, dogs, and monkeys) and shows no liabilities in several counterscreening assays, highlighting its potential as a clinically useful antiviral agent.

Discovery and synthesis of HIV integrase inhibitors: Development of potent and orally bioavailable N-methyl pyrimidones

The human immunodeficiency virus type-1 (HIV-1) encodes three enzymes essential for viral replication: a reverse transcriptase, a protease, and an integrase. The latter is responsible for the integration of the viral genome into the human genome and, therefore, represents an attractive target for chemotherapeutic intervention against AIDS. A drug based on this mechanism has not yet been approved. Benzyl-dihydroxypyrimidine-carboxamides were discovered in our laboratories as a novel and metabolically stable class of agents that exhibits potent inhibition of the HIV integrase strand transfer step. Further efforts led to very potent compounds based on the structurally related N-Me pyrimidone scaffold. One of the more interesting compounds in this series is the 2-N-Me-morpholino derivative 27a, which shows a CIC95 of 65 nM in the cell in the presence of serum. The compound has favorable pharmacokinetic properties in three preclinical species and shows no liabilities in several counterscreening assays.

4,5-Dihydroxypyrimidine carboxamides and N-alkyl-5-hydroxypyrimidinone carboxamides are potent, selective HIV integrase inhibitors with good pharmacokinetic profiles in preclinical species

The dihydroxypyrimidine carboxamide 4a was discovered as a potent and selective HIV integrase strand transfer inhibitor. The optimization of physicochemical properties, pharmacokinetic profiles, and potency led to the identification of 13 in the dihydroxypyrimidine series and 18 in the N-methylpyrimidinone series having low nanomolar activity in the cellular HIV spread assay in the presence of 50% normal human serum and very good pharmacokinetics in preclinical species.

POLYHETEROCYCLIC COMPOUNDS AND THEIR USE AS METABOTROPIC GLUTAMATE RECEPTOR ANTAGONISTS

The present invention relates to new compounds of formula (I), wherein P, Q, X1, X2, X3, X4, X5, X6, R1, R2, R3, m, n, and p are as defined as in formula (I), or salts, or hydrates thereof, processes for their preparation and new intermediates used in the preparation thereof, pharmaceutical compositions containing said compounds and to the use of said compounds in therapy.