2975-41-9

-

Direct and selective synthesis of primary amines from easily available precursors is attractive yet challenging. Herein, we report the rapid synthesis of primary amines from alkenes via metal-free regioselective hydroamination at room temperature. Ammonium carbonate was used as ammonia surrogate for the first time, allowing for efficient conversion of terminal and internal alkenes into linear, α-branched, and α-tertiary primary amines under mild conditions. This method provides a straightforward and powerful approach to a wide spectrum of advanced, highly functionalized primary amines which are of particular interest in pharmaceutical chemistry and other areas.

Half-sandwich iridium complexes bearing bidentate urea-phosphorus ligands were found to catalyze the direct reductive amination of aromatic and aliphatic ketones under mild conditions at 0.5 mol % loading with high selectivity towards primary amines. One of the complexes was found to be active in both the Leuckart–Wallach (NH4CO2H) type reaction as well as in the hydrogenative (H2/NH4AcO) reductive amination. The protocol with ammonium formate does not require an inert atmosphere, dry solvents, as well as additives and in contrast to previous reports takes place in hexafluoroisopropanol (HFIP) instead of methanol. Applying NH4CO2D or D2 resulted in a high degree of deuterium incorporation into the primary amine α-position.

The invention provides a novel method for synthesizing 2-amine indene. The novel method includes carrying out nucleophilic substitution reaction on bisbenzene and ethyl cyanoacetate and carrying out decarboxylation procedures to obtain compounds 15; carrying out hydrolysis to obtain compounds 16; ultimately carrying out Hofmann degradation reaction to obtain the 2-amine indene which is a target product. The bisbenzene is a chemical material and is used as a main raw material for the 2-amine indene. Compared with the prior art, the novel method has the advantages that the novel method is shortin reaction path and suitable for industrial large-scale production, raw materials are low in cost and are easily available, reaction conditions are mild, the productivity can be obviously improved, and the production cycle can be obviously shortened.

The invention relates to a synthetic route of indan-2-amine. 2-indanone is taken as a raw material to efficiently synthesize indan-2-amine by a one-pot method. The provided preparation method of indan-2-amine is high in yield and low in cost, is environmentally friendly, is easy to operate, and is suitable for industrialization.

An innovative approach to position-selective polyhalogenation of aliphatic hydrocarbon bonds is presented. The reaction proceeded within the Hofmann-L?ffler manifold with amidyl radicals as the sole mediators to induce selective 1,5- and 1,6-hydrogen-atom transfer followed by halogenation. Multiple halogenation events of up to four innate C?H bond functionalizations were accomplished. The broad applicability of this new entry into polyhalogenation and the resulting synthetic possibilities were demonstrated for a total of 27 different examples including mixed halogenations.

The invention relates to a synthetic method for indan-2-amine. According to the synthetic method, the target product indan-2-amine is obtained by the following steps: adopting 2-indanone as a raw material, performing substitution reaction on 2-indanone and a halogenated agent to obtain a compound I, performing reduction reaction on the compound I to obtain a compound II, and finally performing amination reaction. Compared with the prior art, the synthetic method provided by the invention has the advantages that the related reactions are simple, the after-treatment is convenient, the raw material is cheap and easy to obtain, the yield is relatively high, and the reaction conditions are mild, thereby being relatively ideal for indan-2-amine preparation.

The invention provides a substituted cyclic compound as well as a use method and application thereof. The compound is a compound as shown in a formula (I) or stereoisomers, stereomers, tautomers, nitric oxides, solvates, metabolites and pharmaceutically acceptable salts or prodrugs of the compound as shown in the formula (I). The invention further provides a medicament composition containing the compound. The compound and the medicament composition are capable of regulating the activity of protein kinase in a biological sample body and are used for protecting, treating or relieving proliferative diseases of patients. The formula (I) is as shown in the specification.

The present invention provides novel substituted alkynyl compounds, pharmaceutical acceptable salts and formulations thereof useful in modulating the protein tyrosine kinase activity, and in modulating cellular activities such as proliferation, differentiation, apoptosis, migration and invasion. The invention also provides pharmaceutically acceptable compositions comprising such compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.

This invention comprises the novel compounds of formula (I) wherein R1, R2, R3, R4, R5, R6, X1 and X2 have defined meanings, having cell cycle kinase inhibiting enzymatic activity, their preparation, compositions containing them and their use as a medicine.

1,2,4-Triphenylbenzene and 2,2′-methylenedioxy-1,1′ -binaphthalene successfully photosensitized the aminations of 1,2-benzo-1,3-cycloalkadienes, arylcyclopropanes, and quadricyclane with ammonia and primary amines in the presence of m- or p-dicyanobenzene, which gave the 4-amino-1,2-benzocycloalkenes, 3-amino-1-arylpropanes, and 7-amino-5-(p-cyanophenyl)bicyclo[2.2.1]hept-2-ene, respectively. A key pathway for the photosensitized amination is the hole transfer from the cation radicals of the sensitizers that were generated by photoinduced electron transfer to the electron acceptors to the substrates. Therefore, it was found that the relationships in oxidation potentials between the sensitizers and the substrates and the positive charge distribution of the cation radicals of the substrates were important factors for the efficient amination.

4-Methoxy acetophenone oximes substituted at the oxygen with TMS, TBS, TIPS and MDPS groups were reduced with borane-THF obtaining the 4-methoxy-N-ethyl aniline as the principal product, up to a 95% yield in the case of the more hindered TIPS group. The 2-methoxy- and 2,4-methoxyacetophenone O-TBS oximes produced only the rearranged secondary aniline. Reduction of 1-indanone O-TBS oximes afforded only the tetrahydroquinoline, whereas the 2-indanone analog provided only 2-aminoindan. (C) 2000 Elsevier Science Ltd.

The photocyclization of N-(2-arylethyl)phthalimides to 4-aryl-2-benzazepine-1,5-diones is described.We found that the presence of electron donating substituents on the aryl ring (as in 10a and b) is necessary for the cyclization process to occur.The procedure also allowed synthesis of 2-benzazepinediones with a carboxylate group at C3 (11c and d) which were obtained as 1:1 mixture of diastereoisomers.The results of irradiating phthalimides 12, which bear an oxygenated substituent at the benzylic position, depended on the nature of the substituent.Attempts to photocyclize N-(indan-2-yl)phthalimides 16 and the electron-rich phthalimide 23 failed.

N,N-Dichloro-t-butylcarbamate (1) reacts with alkenes (2) in a regio- and stereo-selective manner to give the trans-chlorocarbamate adducts (3).Treatment of (3) with base gives aziridines (5), and reaction of (3) and (5) with sodium azide leads selectively to the versatile diamine precursors (6) and (7).In situ reduction of (3) with Zn/NH4OAc leads directly to Boc-protected amines (10).

Cr(ClO4)2 has been shown to be a highly efficient reductant of the anticancer agent, mitomycin C (1). Two different Cr(ClO4)2-mediated reductive techniques were developed and utilized in buffered water and methanolic solutions. In the first procedure, Cr(ClO4)2 (1-2 equiv) was directly added to 1 at various "pH" values. Key observations included the following: (1) Consumption of mitomycin C was rapid and generated as the major products trans- and cis-10-decarbamoyl-1-hydroxy-2,7-diaminomitosenes (11 and 12), and trans- and cis-10-decarbamoyl-1,10-dimethoxymitosenes (16 and 17) in acidic-to-neutral aqueous and methanolic solutions, respectively. (2) Between "pH" 6.0 and 7.0, the difunctionalized mitosene adducts accounted for nearly half of the product profile even though noticeable amounts of unreacted 1 remained. (3) Significant amounts of C-1 electrophilic products were not observed under acidic conditions. The product profiles observed with the second Cr(ClO4)2-mediated reductive procedure were markedly different. Activation of 1 was accomplished by the prior addition of Cr(ClO4)2 to excess cis-10-decarbamoyl-1,10-dimethoxy mitosene (17) to generate the putative mitosene monochromate 20 and mitosene dichromate 21 species in situ, followed by the addition of 1 (1 equiv per Cr(ClO4)2). The products obtained by using this protocol were similar to those observed with conventional reductants in which C-1 electrophilic adducts predominated in acid, C-1 nucleophilic products were the major products under neutral and basic conditions, and little modification of the C-10 site was detected throughout the "pH" range examined. The product profiles coupled with select auxiliary experiments have provided information concerning the mechanism of both reductive procedures. The major products furnished by using the direct Cr(ClO4)2-mediated procedure under acidic and neutral conditions have been attributed to the two one-electron reductions of 1 to give the bis-CrIII-bound species 22. Complexation of the C-5 and C-8 phenolic-type oxygens in reduced 1 is believed to facilitate the loss of methanol at C-9 and C-9a in 1 and the nucleophilic substitution processes at C-1 and C-10 as well as inhibit the electrophilic transformations at both DNA bonding sites. Explanations and supporting data have also been provided to account for the other products detected in these reactions. Correspondingly, the second procedure is conjectured to occur by an outer-sphere electron-transfer process from 20 and/or 21 to 1 to give the uncomplexed hydroquinone (or semiquinone) mitomycin C species 2. Subsequent loss of methanol at C-9 and C-9a yields the activated mitosene capable of furnishing the C-1 functionalized adducts 7 and 9 + 10. The distinctive product profiles observed with the direct addition of Cr(ClO4)2 to 1 and the remarkable high yields of C-1, C-10 dinucleophilic substitution adducts suggest that similar pathways may be operative in the in vivo process to provide the DNA-mitomycin C cross-link adducts. These notions are discussed in light of the DNA sequence selectivity recently observed for the drug monoalkylation bonding process.