1212342-08-9

Basic information

• Product Name: N-CBZ-TRANS-4-FLUORO-L-PROLINONITRILE
• Synonyms: N-CBZ-TRANS-4-FLUORO-L-PROLINONITRILE;Z-TRANS-4-FLUORO-L-PROLINONITRILE;1-Benzyloxycarbonyl-(2S,4R)-2-cyano-4-fluoropyrrolidine, 97%
• CAS NO: 1212342-08-9
• Molecular Formula: C13H13FN2O2
• Molecular Weight: 248.25
• Mol File: 1212342-08-9.mol
• Article Data: 3

Chemical Properties

• Appearance: /
• CAS DataBase Reference: N-CBZ-TRANS-4-FLUORO-L-PROLINONITRILE(CAS DataBase Reference)
• NIST Chemistry Reference: N-CBZ-TRANS-4-FLUORO-L-PROLINONITRILE(1212342-08-9)
• EPA Substance Registry System: N-CBZ-TRANS-4-FLUORO-L-PROLINONITRILE(1212342-08-9)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• Hazardous Substances Data: 1212342-08-9(Hazardous Substances Data)

Upstream product

• 13504-85-3 (2S,4R)-1-(benzyloxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid 
• 1235447-42-3 (2S,4S)-N-Cbz-4-fluoropyrrolidine-2-carbonyl fluoride 

Relevant articles and documents

4-fluoropyrrolidine-2-carbonyl fluorides: Useful synthons and their facile preparation with 4-tert-butyl-2,6-dimethylphenylsulfur trifluoride

4-Fluoropyrrolidine derivatives are useful in medicinal chemistry applications such as dipeptidyl peptidase IV inhibitors. As attractive synthons for these, N-protected (2S,4S)-4-fluoropyrrolidine-2-carbonyl fluorides were synthesized in high yield by double fluorination of N-protected (2S,4R)-4-hydroxyproline with 4-tert-butyl-2,6-dimethylphenylsulfur trifluoride (Fluolead). The 4-fluoropyrrolidine-2-carbonyl fluorides were converted to useful intermediates such as 4-fluoropyrrolidine-2-carboxamides, -N-methoxy-N-methylcarboxamide (Weinreb amide), -carboxylate methyl esters, and -carbonitriles in excellent yields. The crystalline N-Fmoc-cis-4- fluoropyrrolidine-2-carbonyl fluoride 2a is a particularly useful synthon due to its high yield of preparation and easy isolation as an enantiomerically pure compound by crystallization. Thus, the methodology using the synthons prepared by the stereospecific double fluorination has enabled a significant decrease in the synthetic steps needed for the preparation of the 4-fluoropyrrolidine derivatives useful for medicinal applications.

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.