57816-95-2

Upstream product

• 302-17-0 chloral hydrate 
• 643-28-7 2-isopropylaniline 

Downstream Products

• 154551-48-1 2-amino-3-(propan-2-yl)benzoic acid 
• 57816-97-4 7-isopropylindoline-2,3-dione 

Relevant academic research and scientific papers

Enantioselective synthesis of tunable chiral pyridine-aminophosphine ligands and their applications in asymmetric hydrogenation

A small library of tunable chiral pyridine-aminophosphine ligands were enantioselectively synthesized based on chiral 2-(pyridin-2-yl)-substituted 1,2,3,4-tetrahydroquinoline scaffolds, which were obtained in high yields and with excellent enantioselectivities via ruthenium-catalyzed asymmetric hydrogenation of 2-(pyridin-2-yl)quinolines. The protocol features a wide substrate scope and mild reaction conditions, enabling scalable synthesis. These chiral P,N ligands were successfully applied in the Ir-catalyzed asymmetric hydrogenation of benchmark olefins and challenging seven-membered cyclic imines including benzazepines and benzodiazepines. Excellent enantio- and diastereoselectivity (up to 99% ee and >20:1 dr), and/or unprecedented chemoselectivity were obtained in the asymmetric hydrogenation of 2,4-diaryl-3H-benzo[b]azepines and 2,4-diaryl-3H-benzo[b][1,4]diazepines.

Hydrogen bonding behavior of amide-functionalized α-diimine palladium complexes

A class of (N,N′-diaryl-α-diimine)Pd complexes bearing amide substituents on the N-aryl rings is described. Hydrogen bonding interactions involving the amide groups influence the structures, isomer distributions, and ligand coordination behavior of these compounds. The amide-functionalized α-diimine ligands (2,6-iPr2-Ph)N=CMeCMe=N(2-C(=O)NMe2-6-iPr-Ph) (4a), (2,6-iPr2-Ph)N=CMeCMe=N(2,6-(C(=O)NMe2)2-Ph) (4b), and (2-C(=O)NMe2-6-iPr-Ph)N=CMeCMe=N(2-C(=O)NMe2-6-iPr-Ph) (4c) were prepared by condensation reactions of 2,3-butanedione and the appropriate anilines. The attempted preparation of (2,6-iPr2-Ph)N=CMeCMe=N(2-C(=O)NHMe-6-iPr-Ph) (4d) yielded the corresponding 1,2-dihydroquinazolinone derivative 4d′ formed by nucleophilic attack of the amide nitrogen at the proximal imine carbon. 4a and 4b react with (cod)PdMeCl to yield square planar (α-diimine)PdMeCl complexes 5a,a′ and 5b,b′, respectively, which exist as two isomers that differ in the orientation (trans/cis) of the Pd-Me ligand and the amide-substituted arylimine unit. 4c reacts with (MeCN)2PdCl2 and (cod)PdMeCl to yield (4c)PdCl2 (6c-anti,syn) and (4c)PdMeCl (5c-anti,syn), which exhibit anti/syn isomerism due to hindered rotation of the Caryl-N bonds. In the solid state, the amide oxygen atoms in 6c-anti and 5c-syn engage in hydrogen bonding with cocrystallized CH2Cl2 solvent molecules. 4d′ reacts with (MeCN)2PdCl2 via ring-opening metalation to afford the α-diimine complex (4d)PdCl2 (6d). Transmetalation of 6d with SnMe4 yields (4d)PdMeCl (5d,d′) as a mixture of trans and cis isomers. The reaction of 5d,d′ with AgOAc yields (4d)PdMe(OAc) (7d) as a single isomer in which the Pd-Me group is trans to the amide-functionalized arylimine unit. 5d, 6d, and 7d exhibit intramolecular N-H···Cl and N-H···O hydrogen bonding interactions involving the amide NH units. The reactions of 5a,a′, 5c-anti, and 5d,d′ with AgSbF6 in the presence of pyrazole yield the corresponding (α-diimine)PdMe(pz)+SbF6- salts (8a,c,d; pz = pyrazole), which exhibit an intramolecular hydrogen bond between the amide oxygen and the pyrazole NH unit. 8a,c,d undergo partial dissociation of pyrazole in CD3CN solution to generate the corresponding CD3CN complexes 9a,c,d. The non-hydrogen-bonded complex {(2,6-iPr2-Ph)N=CMeCMe=N(2,6-iPr2-Ph)}PdMe(pz)+SbF6- (8e) and its pyrazole dissociation product {(2,6-iPr2-Ph)N=CMeCMe=N(2,6-iPr2-Ph)}PdMe(CD3CN)+SbF6- (9e) were generated in a similar fashion. The pyrazole dissociation constants, Keq = [(α-diimine)PdMe(CD3CN)+] × [pz] × [(α-diimine)PdMe(pz)+]-1, vary in the order 8e > 8d > 8a > 8c, span more than 2 orders of magnitude, and reflect the enhancement of pyrazole binding in 8a,c,d by amide-pyrazole hydrogen bonding. The intramolecular hydrogen bonding in 8c strengthens pyrazole binding by a factor of ca. 120 (i.e., ΔΔG = 2.8(1) kcal mol-1) relative to the case of 8e.

Discovery of 2-[1-(4-Chlorophenyl)cyclopropyl]-3-hydroxy-8- (trifluoromethyl)quinoline-4-carboxylic acid (PSI-421), a P-selectin inhibitor with improved pharmacokinetic properties and oral efficacy in models of vascular injury

Previously, we reported the discovery of PSI-697 (1a), a C-2 benzyl substituted quinoline salicylic acid-based P-selectin inhibitor. It is active in a variety of animal models of cardiovascular disease. Compound 1a has also been shown to be well tolerated and safe in healthy volunteers at doses of up to 1200 mg in a phase 1 single ascending dose study. However, its oral bioavailability was low. Our goal was to identify a back up compound with equal potency, increased solubility, and increased exposure. We expanded our structure-activity studies in this series by branching at the α position of the C-2 benzyl side chain and through modification of substituents on the carboxylic A-ring of the quinoline. This resulted in discovery of PSI-421 with marked improvement in aqueous solubility and pharmacokinetic properties. This compound has shown oral efficacy in animal models of arterial and venous injury and was selected as a preclinical development compound for potential treatment of such diseases as atherosclerosis and deep vein thrombosis.

Deamination of 1-alkyl-9-aminomethyltriptycenes. Participation of a neighboring 1-alkyl substituent

Deamination reactions of 1-alkyl-9-aminomethyltriptycenes (alkyl = Me, Et, i-Pr, and t-Bu) and 9-(1-aminoethyl)-1-methyltriptycene were performed in CHCl3 and in AcOH, and product distributions were studied. The results suggest that the loss of