186249-76-3

Upstream product

• 31562-43-3 tert-butylsulfinyl chloride 
• 100-52-7 benzaldehyde 
• 196929-78-9 (R)-2-methylpropane-2-sulfinamide 
• 1279696-96-6 (2R,4S)-3-[(4-methylphenyl)sulfonyl]-4-(phenylmethyl)-1,2,3-oxathiazolidine 2-oxide 
• 677-22-5 tert-butylmagnesium chloride 
• 4039-32-1 lithium hexamethyldisilazane 
• 159263-57-7 (R)-3-deoxy-1,2:5,6-di-O-isopropylidene-α-D-glucofuranos-3-yl tert-butanesulfinate 

Downstream Products

• 196929-93-8 (R_S,R)-N-(2-methyl-1-phenylpropyl)-2-methylpropane-2-sulfinamide 
• 196929-98-3 (R_S,S)-N-(2-methyl-1-phenylpropyl)-2-methylpropylsulfinamide 
• 1023743-85-2 (R_S,R)-N-(1-phenylallyl)-2-methylpropylsulfinamide 
• 10277-86-8 (R)-1-phenylethylamine hydrochloride 
• 17279-30-0 (S)-(-)-α-methylbenzylamine hydrochloride 
• 19068-33-8 (R)-1-phenylpropan-1-amine hydrochloride 
• 19146-52-2 (1S)-1-phenylpropan-1-amine hydrochloride 
• 1181394-16-0 (R)-1-phenylprop-2-en-1-amine hydrochloride 
• 1181394-16-0 (S)-1-phenylprop-2-en-1-amine hydrochloride 
• 439695-64-4 (R(S))-N-((R)-1-(4-chlorophenyl)-1-phenylmethyl)-2-methylpropane-2-sulfinamide 
• 439695-63-3 (R_S,S)-(1-(4-chlorophenyl)-1-phenylmethyl)-2-methylpropanesulfinamide 
• 451503-36-9 (R_S,R)-(1-(4-methoxyphenyl)-1-phenylmethyl)-2-methylpropanesulfinamide 
• 451503-35-8 (R_S,R)-(1-(4-methylphenyl)-1-phenylmethyl)-2-methylpropanesulfinamide 

Relevant academic research and scientific papers

Synthesis of enantiomerically pure N-tert-butanesulfinyl imines (tert- butanesulfinimines) by the direct condensation of tert-butanesulfinamide with aldehydes and ketones

Experimental details for the first general methods for the one-step preparation of N-tert-butanesulfinyl imines (tert-butanesulfinimines) (2) from aldehydes and ketones is described. To effect the condensations of tert- butanesulfinamide (1) with aldehydes, the Lewis acidic dehydrating agents MgSO4, CuSO4, or Ti(OEt)4 are employed. Aldehyde condensations mediated by MgSO4 proceed in high yields (84-96%) when an excess of aldehyde is used. In contrast, only a slight excess of aldehyde (1.1 equiv) relative to tert- butanesulfinamide provides sulfinimines in high yields when the more Lewis acidic dehydrating agent CuSO4 is used. The CuSO4-mediated procedure is effective for a wide range of aldehydes, including sterically demanding aldehydes, such as isobutyraldehyde (90%), and electron-rich aldehydes, such as p-anisaldehyde (81%). The still more Lewis acidic Ti(OEt)4 and TI(O-i- Pr)4 also afford N-tert-butanesulfinyl aldimines from especially unreactive aldehydes, such as pivaldehyde (82%). In addition, Ti(OEt)4 is effective for the condensation of 1 with ketones to afford a wide range of N-tert- butanesulfinyl ketimines in good yields (77-91%). For sulfinyl ketimines derived from methyl or n-alkyl phenyl ketones and methyl or n-alkyl isopropyl ketones, only the E isomer is detected by 1H and 13C NMR in CDCl3. For those cases where the difference in steric demand about the imine is very small, such as for 2-hexanone, high E/Z ratios are still observed (5:1).

Diastereoselectivity of the Addition of Propargylic Magnesium Reagents to Fluorinated Aromatic Sulfinyl Imines

The addition of propargylmagnesium bromide to fluorinated aromatic sulfinyl imines gave homopropargyl amines with total regio- and diastereoselection. Complete reversal of diastereoselectivity can be achieved in some cases using coordinating (THF) or noncoordinating (DCM) solvents. Substituted propargylic magnesium reagents have been also tested toward fluorinated aryl sulfinyl imines affording chiral homoallenyl amines with good yields and selectivity control. DFT calculations helped to rationalize the origin of the experimental regio- and diastereoselectivities observed in each case.

COVALENT RAS INHIBITORS AND USES THEREOF

The disclosure features compounds, or pharmaceutically acceptable salts thereof, alone and in combination with other therapeutic agents, pharmaceutical compositions, and protein conjugates thereof, capable of modulating biological processes including Ras, and their uses in the treatment of cancers.

RAS INHIBITORS

The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.

Design and Synthesis of TY-Phos and Application in Palladium-Catalyzed Enantioselective Fluoroarylation of gem-Difluoroalkenes

The first example of highly enantioselective fluoroarylation of gem-difluoroalkenes with aryl halides is presented by using a new chiral sulfinamide phosphine (Sadphos) type ligand TY-Phos. N-Me-TY-Phos can be easily synthesized on a gram scale from readily available starting materials in three steps. Salient features of this work including readily available starting materials, good yields, high enantioselectivities as well as broad substrate scope make this approach very practical and attractive. Notably, the asymmetric synthesis of an analogue of a biologically active molecule is also reported.

Indium mediated allylation of WteRR-butanesulftnyl imines with 1,3-dibromopropene: Stereoselective synthesis of aziridines

- The reaction of TV-fer?-butanesulfinyl imines 1 with 1,3-dibromopropene (2), in the presence of indium metal, in saturated aqueous solution of sodium bromide, produced bromohomoallylamine derivatives 3 with total facial diastereoselectivity for the imine addition, and moderate yields. These compounds were easily transformed into the corresponding vinyl aziridines 5 upon deprotonation with KHMDS in THF, the intramolecular cyclization taking place in a stereospecific manner in moderate to high yields.

Asymmetric radical alkylation of: N -sulfinimines under visible light photocatalytic conditions

In this communication, a new photocatalytic strategy for the addition of alkyl-radical derivatives to N-sulfinimines with complete diastereoselectivity and moderate to good yields is presented. This is the first asymmetric photocatalytic addition to N-sulfinimines under visible light irradiation with smooth conditions and functional group tolerance.

Stereoselective Coupling of N-tert-Butanesulfinyl Aldimines and β-Keto Acids: Access to β-Amino Ketones

The reaction of chiral N-tert-butanesulfinyl aldimines with β-keto acids under basic conditions at room temperature proceeds with high levels of diastereocontrol, leading to β-amino ketones in high yields. Based on DFT calculations, an eight-membered cyclic transition state involving coordination of the lithium atom to the oxygens of carboxylate and sulfinyl units was proposed, being in agreement with the observed experimental diastereomeric ratios. The synthesis of the piperidine alkaloid (-)-pelletierine was successfully undertaken in order to demonstrate the utility of this methodology.

2,2- and 2,6-diarylpiperidines by aryl migration within lithiated urea derivatives of tetrahydropyridines

2-Aryltetrahydropyridines formed by anionic cyclization or ring-closing metathesis were converted to their N′-aryl urea derivatives. Depending on the position of the unsaturation within the tetrahydropyridine ring, metalation by deprotonative lithiation or carbolithiation led to migration of the N′-aryl substituent to the 2- or 6-position via intramolecular nucleophilic attack of a benzylic organolithium on the aryl ring. The products are a range of 2,2-, 2,2,3-, and 2,6-polysubstituted piperidine derivatives. Related chemistry was observed in pyrroline homologues.

DMAP-Catalysed Sulfinylation of Diacetone- D -Glucose: Improved Method for the Synthesis of Enantiopure tert-Butyl Sulfoxides and tert-Butanesulfinamides

An improved method for the tert-butanesulfinylation of diacetone glucose with tert-butanesulfinyl chloride is reported. The method is based on a beneficial effect of catalytic DMAP, which enhances both the rate of the reaction and the enantioselectivity of the process to give (R S)-diastereomer 2 R S with a 94 % de and in quantitative yield. (R S)-DAG sulfinate ester 2 R S is an excellent intermediate for the synthesis of enantiopure tert-butyl sulfoxides. Grignard agents and organolithium reagents can displace smoothly the diacetone glucose moiety to give synthetically relevant enantiopure sulfoxides, including highly functionalized derivatives, in high yields and with high enantioselectivities. (R S)-DAG sulfinate ester 2 R S is also an excellent N-sulfinylating agent; simple addition of LiHMDS (lithium hexamethyldisilazide) in THF gives (S S)-tert-butanesulfinamide, and N-tert-butanesulfinylimines are then formed in a two-step one-pot manner. N-Alkylated tert-butanesulfinamides are formed by the condensation of 2 R S with lithium amides.