157007-54-0

Usage

Uses

Used in Pharmaceutical Research and Development:
(R)-1-BOC-2-METHYL-PYRROLIDINE is used as a building block in the synthesis of pharmaceutical intermediates and active ingredients. Its chiral nature and BOC protecting group contribute to the development of enantiomerically pure compounds, which are essential for the efficacy and safety of many drugs.
Used in Organic Synthesis:
As a versatile chemical compound, (R)-1-BOC-2-METHYL-PYRROLIDINE is used as a chiral auxiliary in asymmetric synthesis. This allows for the selective formation of specific enantiomers, which is crucial in obtaining desired biological activities and minimizing potential side effects in synthesized compounds.
Used in Agrochemical Production:
(R)-1-BOC-2-METHYL-PYRROLIDINE finds applications in the production of agrochemicals, where its chemical reactivity and chiral properties are utilized to create effective and selective pesticides or other agricultural chemicals.
Used in Specialty Chemicals Industry:
Due to its unique properties, (R)-1-BOC-2-METHYL-PYRROLIDINE is also employed in the synthesis of specialty chemicals, which are used in various industries such as coatings, adhesives, and fragrances, where specific chemical and physical properties are required.

Upstream product

• 77-78-1 dimethyl sulfate 
• 132482-09-8 tert-butyl (2S)-2-{[(methylsulfonyl)oxy]methyl}-pyrrolidine-1-carboxylate 
• 69610-40-8 N-(tert-butoxycarbonyl)-L-prolinol 
• 24424-99-5 di-tert-butyl dicarbonate 
• 765-38-8 (R)-(-)-2-methylpyrrolidine 
• 86953-79-9 tert-butyl pyrrolidine-1-carboxylate 
• 15761-39-4 1-(tert-butoxycarbonyl)-L-proline 
• 338945-22-5 (S)-2-iodomethyl-pyrrolidine-1-carboxylic acid tert-butyl ester 
• 74-88-4 methyl iodide 

Downstream Products

• 878809-88-2 4-((R)-4-(5-bromo-3-methylpyridin-2-yl)-2-methylpiperazin-1-yl)-6-(4-fluorophenyl)-2-((R)-2-methylpyrrolidin-1-yl)pyrimidine 
• 204387-55-3 (R)-(+)-2-methylpyrrolidine p-toluenesulfonate 
• 765-38-8 (R)-(-)-2-methylpyrrolidine 
• 204386-76-5 rovatirelin 
• 460746-46-7 4-{2-[2-(2R-methylpyrrolidin-1-yl)ethyl]benzofuran-5-yl}benzonitrile 
• 41720-98-3 (R)-2-methylpyrrolidine hydrochloride 

Relevant academic research and scientific papers

Efficient and practical synthesis of (R)-2-methylpyrrolidine

An efficient, practical, and high yielding synthesis of (R)-2-methylpyrrolidine is described. The sequence allows for the scalable preparation of the target compound in just four synthetic steps and proceeds in 83% overall yield and >99% optical purity from readily available starting materials.

Synthesis and evaluation of in vivo anti-hypothermic effect of all stereoisomers of the thyrotropin-releasing hormone mimetic: Rovatirelin Hydrate

We discovered the orally active thyrotropin-releasing hormone (TRH) mimetic: (4S,5S)-5-methyl-N-{(2S)-1-[(2R)-2-methylpyrrolidin-1-yl]-1-oxo-3-(1,3-thiazol-4-yl)propan-2-yl}-2-oxo-1,3-oxazolidine-4-carboxamide 1 (rovatirelin). The central nervous system (CNS) effect of rovatirelin after intravenous (iv) administration is 100-fold higher than that of TRH. As 1 has four asymmetric carbons in its molecule, there are 16 stereoisomers. We synthesized and evaluated the anti-hypothermic effect of all stereoisomers of 1, which has the (4S),(5S),(2S),(2R) configuration from the N-terminus to the C-terminus, in order to clarify the structure?activity relationship (SAR) of stereoisomers. The (4R),(5R),(2R),(2S)-isomer 16 did not show any anti-hypothermic effect. Only the (4S),(5S),(2S),(2S)-isomer 10, which has the (2S)-2-methylpyrrolidine moiety at the C-terminus showed the anti-hypothermic effect similar to 1. Stereoisomers, which have the (5R) configuration of the oxazolidinone at the N-terminus and the (2R) configuration at the middle-part, showed a much lower anti-hypothermic effect than that of 1. On the other hand, stereoisomers, which have the (4R) configuration of the oxazolidinone at the N-terminus or the (2S) configuration of the C-terminus, have little influence on the anti-hypothermic effect.

Asymmetric lithiation trapping of N -boc heterocycles at temperatures above -78°C

The asymmetric lithiation trapping of N-Boc heterocycles using s-BuLi/chiral diamines at temperatures up to -20°C is reported. Depending on the N-Boc heterocycle, lithiation is accomplished using s-BuLi and (-)-sparteine or the (+)-sparteine surrogate in the temperature range -50 to -20°C for short reaction times (2-20 min). Subsequent electrophilic trapping or transmetalation-Negishi coupling delivered functionalized N-Boc heterocycles in 47-95% yield and 77:23-93:7 er. With N-Boc pyrrolidine, trapped products can be generated in ～90:10 er even at -20°C.

Asymmetric synthesis of chiral cyclic amine from cyclic imine by bacterial whole-cell catalyst of enantioselective imine reductase

Streptomyces sp. GF3587 and 3546 were found to be imine-reducing strains with high R- and S-selectivity by screening using 2-methyl-1-pyrroline (2-MPN). Their whole-cell catalysts produced 91 mM R-2-methylpyrrolidine (R-2-MP) with 99.2%e.e. and 27.5 mM S-2-MP (92.3%e.e.) from 2-MPN at 91-92% conversion in the presence of glucose, respectively.

MODULATORS OF THE HISTAMINE H3-RECEPTOR USEFUL FOR THE TREATMENT OF DISORDERS RELATED THERETO

The present invention relates to certain biphenyl sulfonamide derivatives of Formula (Ia) and pharmaceutical compositions thereof that modulate the activity of the histamine H3-receptor. Compounds and pharmaceutical compositions thereof are directed to methods useful in the treatment of histamine H3-receptor associated disorders, such as, cognitive disorders, epilepsy, brain trauma, depression, obesity, disorders of sleep and wakefulness such as narcolepsy, hypersomnia, somnolence syndrome, jet lag, sleep apnea and the like, attention deficit hyperactivity disorder (ADHD), schizophrenia, allergies, allergic responses in the upper airway, allergic rhinitis, nasal congestion, dementia, Alzheimer's disease and the like.

An efficient and convergent synthesis of the potent and selective H3 antagonist ABT-239

An efficient and convergent process for the preparation of a potent and selective H3 receptor antagonist, ABT-239, 1A was accomplished with an overall yield of 64%. The key step in the synthesis is a Sonogashira coupling/cyclization reaction of 1-but-3-ynyl-2-(R)-methylpyrrolidine (9) with 4′-hydroxy-3′-iodo-biphenyl-4-carbonitrile (3). Additionally, the key amine component 2-(R)-methylpyrrolidine (7) was effectively synthesized from the readily available Boc-l-prolinol with a simple catalytical hydrogenolysis as the key step. This column chromatography-free process is highlighted by several simple work-up and purification procedures and is amendable to the large-scale preparation of 1A.

OXAZOLE DERIVATIVES AS HISTAMINE H3 RECEPTOR AGENTS, PREPARATION AND THERAPEUTIC USES

The present invention discloses novel aryl oxazole compounds of Formula I (I), or pharmaceutically acceptable salts thereof, which have histamine-H3 receptor antagonist or inverse agonist activity, as well as methods for preparing and using such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising compounds of Formula I as well as methods of using these compositions to treat obesity, cognitive deficiencies, narcolepsy, and other histamine H3 receptor-related diseases. Formula I (I) or a pharmaceutically acceptable salt thereof, wherein: m is independenlly at each occurrence 1, 2, or 3, Z independently represents carbon (substituted with hydrogen or the optional substituents indicated herein) or nitrogen, provided that when Z is nitrogen then R6 is not attached to Z; R1 and R2 are independently -(C1-C7) alkyl(optionally substituted with one to three halogens), or R1 and R2 and the nitrogen to which they are attached form an azetidinyl ring, a pyrrolidinyl ring, or a piperidinyl ring, wherein further the azetidinyl, pyrrolidinyl, or piperidinyl ring so formed may be optionally substituted one to three times with R5; R6 is independently at each occurrence -H, -halogen, or -CH3.

Process for preparing 2-methylpyrrolidine and specific enantiomers thereof

The invention relates to a process for preparing 2-methylpyrrolidine and, more particularly, specific enantiomers of 2-methylpyrrolidine. Novel intermediates also are described.

Process for preparing 2-methylpyrrolidine and specific enantiomers thereof

The invention relates to a process for preparing 2-methylpyrrolidine and, more particularly, specific enantiomers of 2-methylpyrrolidine. Novel intermediates also are described.

Complex-induced proximity effects: The effect of varying directing-group orientation on carbamate-directed lithiation reactions

A series of selected bicyclic carbamates in which the range of accessible angles and distances between the carbonyl group and the proton removed in an α-lithiation reaction are structurally defined have been investigated. Oxazolidinones 7-10 undergo stereoselective lithiation-substitution reactions to provide cis-18-27 and cis-31-35 as the major diastereomers. Two series of competition experiments show that the conformationally restricted carbamates 7, 10, 11, and 15 undergo lithiation via complexes more efficiently than Boc amines 4-6. These results along with semiempirical calculations suggest that a small dihedral angle and a calculated distance of 2.78 A between the carbamate carbonyl oxygen and the proton to be removed are favorable for a carbamate-directed lithiation. A series of tin-lithium exchange experiments on cis- and trans-18 and (S)-39 indicate that the configurational stability of a carbamate-stabilized organolithium species may be enhanced by restrictive geometry.