36635-66-2

Basic information

• Product Name: (1-PHENYL-1-TOSYL)METHYL ISOCYANIDE
• Synonyms: A-TOSYLBENZYL ISOCYANIDE;ALPHA-TOSYLBENZYL ISOCYANIDE;(1-PHENYL-1-TOSYL)METHYL ISOCYANIDE;1-([ISOCYANO(PHENYL)METHYL]SULPHONYL)-4-METHYLBENZENE;alfa-Tosylbenzylisocyanide;1-(isocyano(p-tolyl)methylsulfonyl)-4-methylbenzene;Isocyano(phenyl)methyl 4-methylphenyl sulphone;Benzene,1-[(isocyanophenylMethyl)sulfonyl]-4-Methyl-
• CAS NO: 36635-66-2
• Molecular Formula: C₁₅H₁₃NO₂S
• Molecular Weight: 271.33
• EINECS: 200-258-5
• Product Categories: pharmacetical
• Mol File: 36635-66-2.mol
• Article Data: 11

Chemical Properties

• Melting Point: 106 °C(dec.)
• Appearance: /
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• CAS DataBase Reference: (1-PHENYL-1-TOSYL)METHYL ISOCYANIDE(CAS DataBase Reference)
• NIST Chemistry Reference: (1-PHENYL-1-TOSYL)METHYL ISOCYANIDE(36635-66-2)
• EPA Substance Registry System: (1-PHENYL-1-TOSYL)METHYL ISOCYANIDE(36635-66-2)

Safety Data

• Hazard Codes: Xi
• Hazardous Substances Data: 36635-66-2(Hazardous Substances Data)

Usage

Preparation

A 1-L, three-necked, roundbottomed flask fitted with an overhead stirrer, a 100 mL addition funnel, and a temperature probe was charged with THF (200 mL) and 1615 (27.6 g, 94.8 mmol). Phosphoryl chloride (17.7 mL, 190 mmol) was added and the resulting solution was stirred for 5 min at 25 C°. After cooling the solution to 0 C°, triethylamine (79.3 mL, 569 mmol) was added slowly over 30–45 min while keeping the internal reaction temperature below 10 C°. After the addition of triethylamine was complete, the reaction mixture was warmed to 5–10 C° and maintained at this temperature for 30–45 min. Ethyl acetate (140 mL) and water (140 mL) were added sequentially to the reaction mixture, stirring was continued for 5 min, and then the mixture was transferred to a separatory funnel and the aqueous layer was removed. The organic layer was washed with water (2×140 mL), saturated sodium hydrogen carbonate solution (140 mL), and brine (70 mL). The organic layer was transferred to a 500-mL, round-bottomed flask and concentrated on a rotary evaporator. The residue was diluted with 1-propanol (140 mL) and this solution was concentrated on a rotary evaporator to half of its original volume. The residue was cooled to 5–10 C° for 30 min and the beige solid that crystallized was collected by filtration through a Buchner funnel. The filter cake was rinsed with 1-propanol (2×75 mL). The beige solid was dried in vacuo for 3–4 h to give 18.1–19.7 g (70– 76%) of a-tosylbenzyl isocyanide 1616. Structurally analogous to TosMIC 1600 is PhosMIC 1617, which has a phosphonate residue instead of a sulfonate residue. Some representatives have been described by Bartlett.

InChI:InChI=1/C15H13NO2S/c1-12-8-10-14(11-9-12)19(17,18)15(16-2)13-6-4-3-5-7-13/h3-11,15H,1H3

Upstream product

• 536-57-2 p-toluene sulfinic acid 
• 100-52-7 benzaldehyde 
• 37643-54-2 N-[(4-methylbenzene-1-sulfonyl)(phenyl)methyl]formamide 
• 88333-03-3 Benzyl isocyanide 
• 455-16-3 p-toluenesulfonyl fluoride 

Downstream Products

• 97388-59-5 1,6-diisocyano-1,6-diphenyl-1,6-ditosylhexane 
• 40167-39-3 methyl 4,5-diphenyl-1H-pyrrole-3-carboxylate 
• 88333-03-3 Benzyl isocyanide 
• 874097-07-1 2-(5-but-3-enyl-4-phenyl-imidazol-1-yl)-hex-4-ynoic acid methyl ester 
• 873890-37-0 5-(2-azido-phenyl)-1-but-2-ynyl-4-phenyl-1H-imidazole 
• 873890-38-1 5-(2-azido-phenyl)-4-phenyl-1-(3-phenyl-prop-2-ynyl)-1H-imidazole 
• 1004527-61-0 4-(1-methyl-4-phenyl-1H-imidazol-5-yl)piperidine 
• 459447-62-2 2-Chloro-5-(4-phenyl-oxazol-5-yl)-pyridine 

Relevant articles and documents

Selective N-Terminal BET Bromodomain Inhibitors by Targeting Non-Conserved Residues and Structured Water Displacement**

Bromodomain and extra-terminal (BET) family proteins, BRD2-4 and T, are important drug targets; however, the biological functions of each bromodomain remain ill-defined. Chemical probes that selectively inhibit a single BET bromodomain are lacking, although pan inhibitors of the first (D1), and second (D2), bromodomain are known. Here, we develop selective BET D1 inhibitors with preferred binding to BRD4 D1. In competitive inhibition assays, we show that our lead compound is 9–33 fold selective for BRD4 D1 over the other BET bromodomains. X-ray crystallography supports a role for the selectivity based on reorganization of a non-conserved lysine and displacement of an additional structured water in the BRD4 D1 binding site relative to our prior lead. Whereas pan-D1 inhibitors displace BRD4 from MYC enhancers, BRD4 D1 inhibition in MM.1S cells is insufficient for stopping Myc expression and may lead to its upregulation. Future analysis of BRD4 D1 gene regulation may shed light on differential BET bromodomain functions.

The base-free van Leusen reaction of cyclic imines on water: Synthesis of N-fused imidazo 6,11-dihydro β-carboline derivatives

Construction of imidazoles has been demonstrated on water under base-free conditions. The reaction of dihydro β-carboline imines and p-toluenesulfonylmethyl isocyanides furnished the corresponding substituted N-fused imidazo 6,11-dihydro β-carboline derivatives in very good yields under ambient conditions. The use of deuterium oxide (D2O) as a solvent enabled the incorporation of deuterium isotopes in the imidazole ring.

Catalytic Enantio- and Diastereoselective Mannich Addition of TosMIC to Ketimines

Chiral amines bearing a stereocenter in the α position are ubiquitous compounds with many applications in the pharmaceutical and agrochemical sectors, as well as in catalysis. Catalytic asymmetric Mannich additions represent a valuable method to access such compounds in enantioenriched form. This work reports the first enantio- and diastereoselective addition of commercially available p-toluenesulfonylmethyl isocyanide (TosMIC) to ketimines, affording 2-imidazolines bearing two contiguous stereocenters, one of which is fully-substituted, with high yields and excellent stereocontrol. The reaction, catalyzed by silver oxide and a dihydroquinine-derived N,P-ligand, is broad in scope, operationally simple, and scalable. Derivatization of the products provides enantioenriched vicinal diamines, precursors to NHC ligands and sp3-rich heterocyclic scaffolds. Computations are used to understand catalysis and rationalize stereoselectivity.