33375-06-3

Usage

Uses

Used in Chemical Derivatization:
(R)-(+)-1-Phenylethyl isocyanate is used as a derivatizing agent for alcohols, thiocarbamates, and hydroxy fatty acids. Its ability to form derivatives with these compounds makes it a valuable tool in the synthesis of various chemical products.
Used in Inhibition of BP-DNA Adducts:
(R)-(+)-1-Phenylethyl isocyanate has demonstrated moderate inhibitory effects on BP-DNA adducts, which are harmful chemical compounds that can form covalent bonds with DNA, potentially leading to mutations and other negative effects on cellular function. This application highlights its potential use in the field of pharmaceuticals and biochemistry.

InChI:InChI=1/C9H9NO/c1-8(10-7-11)9-5-3-2-4-6-9/h2-6,8H,1H3/t8-/m1/s1

Upstream product

• 1623-51-4 α-Phenethylcarbamidsaeureethylester 
• 3315-16-0 silver cyanate 
• 585-71-7 (1-bromoethyl)benzne 
• 618-36-0 rac-methylbenzylamine 
• 503-38-8 trichloromethyl chloroformate 
• 75-44-5 phosgene 
• 98-85-1 1-Phenylethanol 
• 39139-87-2 tetrabutylammonium isocyanate 
• 100-42-5 styrene 
• 105966-39-0 2-(1-phenylethoxy)-tetrahydro-2H-pyran 
• 208924-64-5 (±)-N-hydroxy-2-phenylpropanamide 
• 95826-99-6 1-(1H-imidazol-1-yl)-2-phenylpropan-1-one 
• 32315-10-9 bis(trichloromethyl) carbonate 
• 124-38-9 carbon dioxide 

Downstream Products

• 101260-94-0 (1-phenyl-ethyl)-carbamic acid-(2-diethylamino-ethyl ester) 
• 101174-10-1 6β-[3-((Ξ)-1-phenyl-ethyl)-ureido]-penicillanic acid 
• 40589-84-2 1-phenethyl urea 
• 80490-87-5 Piperazine-1,4-dicarboxylic acid bis-[(1-phenyl-ethyl)-amide] 
• 88235-71-6 5-Hydroxyamino-3,4,4-trimethyl-1-(1-phenyl-ethyl)-imidazolidin-2-one 
• 121060-83-1 1-[2-(1-Benzyl-1,2,3,6-tetrahydro-pyridin-4-yl)-4-chloro-phenyl]-3-(1-phenyl-ethyl)-urea 
• 143164-06-1 ((S)-1-Phenyl-ethyl)-carbamic acid (6S,7S)-5,5-dimethyl-7-(2-oxo-piperidin-1-yl)-6,7-dihydro-5H-thieno[3,2-b]pyran-6-yl ester 
• 147169-48-0 (R,S)-N-(tert-butyloxycarbonyl)-α-methylbenzylamine 

Relevant academic research and scientific papers

Resolution of albuterol acetonide

The (R)-enantiomer of albuterol has been isolated via resolution of albuterol acetonide with (2S,3S)-di-O-benzoyl- or (2S,3S)-di-O-toluoyltartaric acid. The absolute configuration of the resolved acetonide was assessed by 1H NMR analysis of its (R)-Mosher's ester, and confirmed by an X-ray crystal structure determination of the (R)-phenylethylurea derivative of the (S)-enantiomer.

Benzylic C-H isocyanation/amine coupling sequence enabling high-throughput synthesis of pharmaceutically relevant ureas

C(sp3)-H functionalization methods provide an ideal synthetic platform for medicinal chemistry; however, such methods are often constrained by practical limitations. The present study outlines a C(sp3)-H isocyanation protocol that enables the synthesis of diverse, pharmaceutically relevant benzylic ureas in high-throughput format. The operationally simple C-H isocyanation method shows high site selectivity and good functional group tolerance, and uses commercially available catalyst components and reagents [CuOAc, 2,2′-bis(oxazoline) ligand, (trimethylsilyl)isocyanate, andN-fluorobenzenesulfonimide]. The isocyanate products may be used without isolation or purification in a subsequent coupling step with primary and secondary amines to afford hundreds of diverse ureas. These results provide a template for implementation of C-H functionalization/cross-coupling in drug discovery.

Amide compound, pharmaceutical composition, preparation method and application thereof

The invention provides an amide compound, a pharmaceutical composition, a preparation method and application thereof and belongs to the field of medicine. Structure of the amide compound is shown as aformula I. The preparation method includes: in an alkaline condition and in an organic solvent, allowing a compound I and a compound II to be in condensation reaction. The amide compound or pharmaceutically acceptable salt thereof have long-acting sensory and/or motion blocking activity, can be used for preparing long-acting local anesthetic or analgesic and is long in efficacy lasting time, little side effect and high in medication safety.

Alkyl Isocyanates via Manganese-Catalyzed C-H Activation for the Preparation of Substituted Ureas

Organic isocyanates are versatile intermediates that provide access to a wide range of functionalities. In this work, we have developed the first synthetic method for preparing aliphatic isocyanates via direct C-H activation. This method proceeds efficiently at room temperature and can be applied to functionalize secondary, tertiary, and benzylic C-H bonds with good yields and functional group compatibility. Moreover, the isocyanate products can be readily converted to substituted ureas without isolation, demonstrating the synthetic potential of the method. To study the reaction mechanism, we have synthesized and characterized a rare MnIV-NCO intermediate and demonstrated its ability to transfer the isocyanate moiety to alkyl radicals. Using EPR spectroscopy, we have directly observed a MnIV intermediate under catalytic conditions. Isocyanation of celestolide with a chiral manganese salen catalyst followed by trapping with aniline afforded the urea product in 51% enantiomeric excess. This represents the only example of an asymmetric synthesis of an organic urea via C-H activation. When combined with our DFT calculations, these results clearly demonstrate that the C-NCO bond was formed through capture of a substrate radical by a MnIV-NCO intermediate.

Structure-activity relationship studies of pyrazolo[3,4-d]pyrimidine derivatives leading to the discovery of a novel multikinase inhibitor that potently inhibits FLT3 and VEGFR2 and evaluation of its activity against acute myeloid leukemia in vitro and in vivo

We describe the structural optimization of a hit compound, 1-(4-(1H-pyrazolo[3,4-d]pyrimidin-4-ylamino)phenyl)-3-(3-methoxyphenyl)urea (1), which exhibits inhibitory activity but low potency against FLT3 and VEGFR2. A series of pyrazolo[3,4-d]pyrimidine derivatives were synthesized, and structure-activity relationship analysis using cell- and transgenic-zebrafish- based assays led to the discovery of a number of compounds that exhibited both high potency against FLT3-driven human acute myeloid leukemia (AML) MV4-11 cells and a considerable antiangiogenic effect in transgenic-zebrafish-based assays. The compound 1-(4-(1H-pyrazolo[3,4-d]pyrimidin -4-yloxy)phenyl)-3-(4-chloro-3- (trifluoromethyl)phenyl)urea (33), which exhibited the highest activity in preliminary in vivo anti-AML assays, was chosen for further anti-AML studies. The results demonstrated that compound 33 is a multikinase inhibitor that potently inhibits FLT3 and VEGFR2. In an MV4-11 xenograft mouse model, a once-daily dose of compound 33 at 10 mg/kg for 18 days led to complete tumor regression without obvious toxicity. Western blot and immunohistochemical analyses were performed to determine the mechanism of action of compound 33.

N-methylimidazole-catalyzed synthesis of carbamates from hydroxamic acids via the lossen rearrangement

An efficient, one-pot, N-methylimidazole (NMI) accelerated synthesis of aromatic and aliphatic carbamates via the Lossen rearrangement is reported. NMI is a catalyst for the conversion of isocyanate intermediates to the carbamates. Moreover, the utility of arylsulfonyl chloride in combination with NMI minimizes the formation of often-observed hydroxamate-isocyanate dimers during the sequence. Under the present conditions, lowering of temperatures is also possible, enabling a mild protocol.

One-pot sequential synthesis of isocyanates and urea derivatives via a microwave-assisted Staudinger-aza-Wittig reaction

A fast and efficient protocol for the synthesis of N,N'-disubstituted urea derivatives from alkyl halides and primary or secondary amines has been developed. The synthetic pathway combines nucleophilic substitutions and a Staudinger-aza-Wittig reaction in the presence of polymer-bound diphenylphosphine under 14 bar of CO2 pressure and has been performed in a one-pot two-step process. The protocol has been optimized under microwave irradiation and the scale-up experiment has been conducted under conventional conditions in a Parr reactor. The final compounds were isolated after simple filtration in almost quantitative overall yields which makes this procedure facile and rapid to execute.

Design, synthesis and evaluation of 1,2-benzisothiazol-3-one derivatives as potent caspase-3 inhibitors

A number of 1,2-benzisothiazol-3-one derivatives were prepared through structural modification of the original compound from high-throughput screening. Some analogues (e.g., 6b, 6r, 6s and 6w) were identified as novel and potent caspase inhibitors with IC50 of nanomolar. Structure-activity relationship (SAR) studies for caspase-3 inhibition were evaluated in vitro. Molecular modeling studies provided further insight into the interaction of this class of compounds with activated caspase-3. The present small molecule caspase-3 inhibitor with novel structures different from structures of known caspase inhibitors revealed a new direction for therapeutic strategies directed against diseases involving abnormally up-regulated apoptosis.

Carbonyldiimidazole-mediated lossen rearrangement

[Chemical Equation Presented] Carbonyldiimidazole (CDI) was found to mediate the Lossen rearrangement of various hydroxamic acids to isocyanates. This process is experimentally simple and mild, with imidazole and CO 2 being the sole stoichiometric byproduct. Significant for large-scale application, the method avoids the use of hazardous reagents and thus represents a green alternative to standard processing conditions for the Curtius and Hofmann rearrangements.

Triphenylphosphine/2,3-dichloro-5,6-dicyanobenzoquinone (DDQ)/[n-Bu4N]OCN as a useful system for the efficient conversion of tetrahydropyranyl (THP) ethers to the corresponding alkyl isocyanates

Triphenylphosphine/2,3-dichloro-5,6-dicyanobenzoquinone/tetrabutylammonium cyanate was used as an efficient system for the conversion of tetrahydropyranyl ethers to the corresponding alkyl isocyanates. Taylor & Francis Group, LLC.