Syntheses of metabolites of ethyl 4-(3,4-dimethoxyphenyl)-6,7-dimethoxy-2-(1,2,4-triazol-1-ylmethyl)quinoline-3-carboxylate (TAK-603)

Convenient and efficient syntheses of ethyl 4-(3-hydroxy-4-methoxyphenyl)-6,7-dimethoxy-2-(1,2,4-triazol-1-ylmethyl)quinoline-3-carboxylate (1d) and 10-(3,4-dimethoxyphenyl)-7,8-dimethoxy-2H-pyridazino[4,5-b]quinolin-1-one (1e), metabolites of TAK-603 (1), have been achieved. Use of the methanesulfonyl as a protective group of the phenolic hydroxy for Friedel-Crafts reaction enabled a new simpler synthetic route of 1d in high yield. Chloromethyl derivative (23) was converted to formyl derivative (32) using the Kröhnke reaction, followed by cyclization with hydrazine, which formed a novel compound 1e.     

Study of some reactions of ethyl 4-phenyl-3-benzoyl-2-pyrazoline-5-carboxylate

Several reactions of the pyrazoline 1a were investigated. With bromine water, potassium permanganate, hydrogen peroxide, or potassium hydroxide, different pyrazole derivatives were formed. While the reaction with hydroxylamine or some hydrazines gave the corresponding pyrazoline Schiff bases, with aroylhydrazines, pyrazole Schiff bases were formed.     

Enzyme-catalysed improved resolution of (RS)-4-cyano-4-(3,4-dimethoxyphenyl)-4-isopropyl-1-butanol

Resolutions of (RS)-4-cyano-4-(3,4-dimethoxyphenyl)-4-isopropyl-1-butanol 1 using various enzymes were performed. Among them, Pseudomonas fluorescens resolved it with moderate stereoselectivity (E=13) and reacted faster with the (S)-enantiomer. To optimize enzyme-catalysed reaction conditions for the resolution, the effect of solvents and additives was studied. In n-hexane:ethyl acetate (9:1), both reaction rate and selectivity were high. When pyridine, potassium carbonate and molecular sieves were used as additives, the enantiomeric excess of the (R)-enantiomer was 99, 99 and 98% at 52–60% conversion, respectively. However, in diisopropyl ether, the enantiomeric excess of unreacted alcohol (R)-1 was up to 99% at 70% conversion without additives.     

1-苯基-5-(3,4-二甲氧基苯基)-3-羟基吡唑的合成和晶体结构

标题化合物(I)是由 1-苯基-5-(3, 4-二甲氧基苯基)-3-吡唑烷酮在 FeCl3催化下被氧气氧化得到的。它的结构经过了元素分析、IR、1H NMR 的表征,用 X-射线衍射法测定了化合物的晶体结构。C17H16N2O3(I)的晶体学参数分别为:三斜晶系,P1空间群,a = 6.6600(13),b = 8.4200(17),c = 14.060(3) ?,α= 85.61(3), β= 76.89(3), γ= 81.18(3)?, Z = 2, Dc= 1.298g/cm3, V = 758.1(3) ?3, Mr = 296.32,μ= 0.090 mm–1, F(000) = 312, R = 0.048,wR = 0.1231。结构测定表明化合物的吡唑环存在着一个大的共轭体系,含有一个稳定的烯醇结构,分子通过分子间的氢键形成了网状的结构。     

Regioselective cycloaddition of C-carbamoylnitrones to methyl (E)-2-(2-phenylcyclopropylidene)acetate and methyl (E)-2-methylidene-3-phenylcyclopropane-1-carboxylate

N-Aryl-C-(arylcarbamoyl)nitrones regioselectively add to methyl 2-(2-phenylcyclopropylidene)-acetate and methyl 2-methylidene-3-phenylcyclopropanecarboxylate to give in each case two diastereoisomeric 5-oxa-6-azaspiro[2.4]heptane-4-carboxylates.     

Synthesis and Crystal Structure of 2-Amino-3-cyano- 4-（3,4-dimethoxyphenyl）-4H-benzo[h]chromenes

1INTRODUCTION4H-Chromeneisaconstructionunitofsomenaturalproducts.4H-Chromeneswithaminoandcyanogroupsarealsosynthonofsomespecialnaturalproducts[1,2].Thesubstituted4H-chromenespossessawiderangeofpharmacologicalactivi-ties[3～5].Inordertoinvestigatetheactivi…     

Synthesis and Crystal Structure of 2-Amino-3-cyano-4-(3,4-dimethoxyphenyl)-4H-benzo[h]chromenes

The title compound (C22H18N2O3) has been synthesized by the reaction of 3,4-dimethoxybenzaldehyde,malononitrile and 1-naphthol in ethanol in the presence of piperidine,and its structure was characterized by elemental analysis,IR,1H NMR and X-ray single-crystal diffraction.The crystal belongs to monoclinic,space group C2/c with a=24.221(6),b=9.016(2),c=17.003(5)A,β=93.16(1)°,V=3707(2)A3,Mr=358.38,Z=8,Dc=1.284g/cm3,μ(MoKα)=0.087mm-1,F(000)=1504,the final R=0.0432 and wR=0.1085.X-ray analysis reveals that the atoms of C(1),C(2),C(3),C(4),C(5) and O(1) form a boat-form six-membered ring in which the C(1)-C(2)(1.349(3)A) is a C=C double bond.     

An unusual product of the reaction of 1-phenyl-3-(3,4-dimethoxyphenyl)-3-(2-oxocyclohexyl)-1-propanone with hydrogen sulfide and acids: 2α-phenyl-2,4-ortho-(14,15-dimethoxybenzo)-cis-1-thiadecalin

The reaction of 1-phenyl-3-(3,4-dimethoxyphenyl)-3-(2-oxocyclohexyl)-1-propanone with hydrogen sulfide and acids gives an intramolecular rearrangement product, 2-phenyl-2,4-ortho-(14,15-dimethoxybenzo)-cis-1-thiadecalin in addition to the usual products of disproportionation of intermediate 2-phenyl-4-(3,4-dimethoxyphenyl)-5,6-tetramethylene-4H-thiopyran, namely, 5,6-tetramethylenethiopyrilium salts and 2-phenyl-4-(3,4-dimethoxyphenyl)-cis-1-thiadecalin. The configurational and conformational assignments for the sulfides, their sulfoxides, and sulfones were made by ¹³C NMR spectroscopy.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 199–205, February, 1986.