- Novel method and technology for synthesizing cyclopropyl ammonia
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The invention discloses a synthesis process route of a cyclopropane synthetic route. In the process route, cyanocyclopropane 1 - formic acid (-1 -) and (1) are subjected to hydrolysis under the action of a strong base to generate 1-cyanocyclopropane 1 - formic acid (-1 -), (2) decarboxylation to generate cyclopropanecarboxamide (2 3), and (4 4 3) subjected to Hoffman rearrangement to obtain the target product cyclopropysite. The process route is longer than the production process in the present stage, the reaction route is long, the use of high-temperature and high-pressure is avoided, the danger is reduced, and the safety is improved. The requirement of the reaction equipment is reduced, the used raw materials are easy to obtain, operation is easy, safety and environmental protection are achieved, and industrial production can be realized.
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Paragraph 0018
(2021/09/21)
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- Modular Continuous Flow Synthesis of Imatinib and Analogues
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A modular continuous flow synthesis of imatinib and analogues is reported. Structurally diverse imatinib analogues are rapidly generated using three readily available building blocks via a flow hydration/chemoselective C-N coupling sequence. The newly developed continuous flow hydration and amidation modules each exhibit a broad scope with good to excellent yields. Overall, the method described does not require solvent switches, in-line purifications, or packed-bed apparatuses due to the judicious manipulation of flow setups and solvent mixtures.
- Fu, Wai Chung,Jamison, Timothy F.
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supporting information
p. 6112 - 6116
(2019/08/26)
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- Method for preparing amide by metallic sodium catalyzed ester ammonolysis reaction
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The invention discloses a method for preparing amide by metallic sodium catalyzed ester ammonolysis reaction. The method is characterized in that ester and liquid ammonia are taken as raw materials, and metallic sodium is taken as a catalyst to perform reaction at a temperature of 90-140 DEG C in a high-pressure kettle; a molar ratio of the ester to ammonium is 1: (1.2 to 5.0); molar weight of the metallic sodium is 4-10% that of the ester; when reaction pressure is not lowered any longer, reaction is stopped to recycle the ammonium which is not reacted; and an obtained reaction product is post-treated to obtain a product. The method can be used for efficiently preparing the amide; and moreover, the raw materials are cheap and are low in toxicity, reaction activity is relatively high, dose of the catalyst is small, reaction speed is high, a reaction conversion rate is high, and the product is easily separated.
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Paragraph 0066
(2017/08/30)
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- Efficient Hydration of Nitriles Promoted by Gallic Acid Derived from Renewable Bioresources
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An efficient gallic acid promoted nitriles hydration at room temperature with ethanol/water as a solvent has been developed. The present protocol offers a wide range of amides in moderate to good yields. Moreover, galla chinensis extract can serve as the promoter to perform the hydration, which also shows the potential utilization of natural feedstocks.
- Deng, Tao,Wang, Cheng-Zhang
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p. 1349 - 1353
(2017/04/14)
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- Corresponding amine nitrile and method of manufacturing thereof
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The invention relates to a manufacturing method of nitrile. Compared with the prior art, the manufacturing method has the characteristics of significantly reduced using amount of an ammonia source, low environmental pressure, low energy consumption, low production cost, high purity and yield of a nitrile product and the like, and nitrile with a more complex structure can be obtained. The invention also relates to a method for manufacturing corresponding amine from nitrile.
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Paragraph 0133-0136; 0165-0169; 0199-0202
(2017/10/22)
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- Clean synthesis of primary to tertiary carboxamides by CsOH-catalyzed aminolysis of nitriles in water
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Using CsOH as the only catalyst and utilizing its "cesium effect", a clean synthesis of a wide range of primary, secondary, and tertiary carboxamides was achieved by aminolysis reactions of nitriles with ammonia, primary, or secondary amines in water. Studies on the control reactions revealed that the reactions with ammonia most probably proceed via an aminolysis path by the initial addition of ammonia to Cs-activated nitriles to form unsubstituted amidine intermediates, while the reactions with primary or secondary amines may proceed via a hydration/transamidation path by the initial hydration of the Cs-activated nitriles to form primary carboxamide intermediates followed by their transamidation with amines through the formation of substituted amidine intermediates.
- Li, Yang,Chen, Haonan,Liu, Jianping,Wan, Xujun,Xu, Qing
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supporting information
p. 4865 - 4870
(2016/10/06)
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- Efficient and selective nitrile hydration reactions in water catalyzed by an unexpected dimethylsulfinyl anion generated in situ from CsOH and DMSO
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Unexpected dimethylsulfinyl anions (I), generated in situ from the superbase system CsOH-DMSO, was found to be a highly active catalyst for controllable nitrile hydration reactions in water, which selectively afforded the versatile amides via interesting Cs-activated I-catalyzed direct and indirect hydration mechanisms involving an O-transfer process from DMSO onto the nitriles. the Partner Organisations 2014.
- Chen, Haonan,Dai, Wujie,Chen, Yi,Xu, Qing,Chen, Jianhui,Yu, Lei,Zhao, Yajuan,Ye, Mingde,Pan, Yuanjiang
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supporting information
p. 2136 - 2141
(2014/04/17)
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- HETEROCYCLIC COMPOUNDS AS PROTEIN KINASE INHIBITORS
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The present invention provides a heterocyclic compound of formula (I), a pharmaceutically acceptable salt thereof, a prodrug thereof or a hydrate thereof, wherein A, A′ B, D, R1, R2 and R3 are as defined herein, a pharmaceutical composition comprising a compound of formula (I) as an active ingredient, methods of production, and methods of use thereof. Particularly, the present invention provides a compound of formula (I) useful for treating or preventing a disease, condition or disorder associated with protein kinases, preferably Janus Kinase family.
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Paragraph 0365
(2014/06/23)
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- HETEROCYCLIC COMPOUNDS AS PROTEIN KINASE INHIBITORS
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The present invention provides a heterocyclic compound of formula (I), a pharmaceutically acceptable salt thereof, a prodrug thereof or a hydrate thereof, wherein A, A' B, D, R1, R2 and R3 are as defined herein, a pharmaceutical composition comprising a compound of formula (I) as an active ingredient, methods of production, and methods of use thereof. Particularly, the present invention provides a compound of formula (I) useful for treating or preventing a disease, condition or disorder associated with protein kinases, preferably Janus Kinase family.
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Page/Page column 59-60
(2012/12/13)
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- 1,2-DISUBSTITUTED CYCLOPROPANES
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Compounds of Formula I wherein the substituents are as described in the specification or pharmaceutically acceptable salts or stereochemically isomeric forms thereof, useful for treating diseases related to calcium imbalance and metabolism.
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- Process for the preparation of cyclopropanecarboxamide
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Cyclopropanecarboxamide can be prepared by reaction of a cyclopropanecarboxylic ester with NH3, in which the ester alcohol has 4-8 C atoms and can be straight-chain or branched and which process is carried out in the presence of catalytic amounts of an alkali metal alcoholate of a monohydric C1-C8 alcohol at 60°-200° C. in the absence of a hydrocarbon solvent.
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- Catalytic Hydration of Nitriles to Amides with Manganese Dioxide on Silica Gel
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Hydration of representative nitriles with silica gel supported manganese dioxide at the reflux temperature of hydrocarbon solvents gives the corresponding amides in good to excellent yield.Phenylacetonitrile, however, was partially oxidized to benzoylformamide.Other manganese catalyst systems were also evaluated.
- Liu, Kwang-Ting,Shih, Mei-Hsiu,Huang, Hsiau-Wen,Hu, Chia-Juei
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p. 715 - 717
(2007/10/02)
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- DIAZEPINOINDOLES USEFUL FOR TREATING DEPRESSION, SCHIZOPHRENIA, SOCIAL WITHDRAWAL OR ANXIETY AND PHARMACEUTICAL COMPOSOTIONS CONTAINING THEM
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Diazepinoindoles or pharmaceutically acceptable acid addition salts thereof are useful as antidepressant, conflict reducing or neuroleptic agents.
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- Scope, Limitation, and Mechanism of the Homoconjugate Electrophilic Addition of Hydrogen Halides
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Hydrogen halides (HCl, HBr, HI) add by a homoconjugate 1,5 mechanism to cyclopropanes carrying certain electron-withdrawing substituents.When the substituent is COCH3, COC6H5, CO2H, or CN, the reaction gives the 1,3-disubstituted propane in high yield.Addition of DCl gives a product with deuterium only in the position α to the substituent.The order of rates is not in agreement with a mechanism whereby the cyclopropane ring is protonated initially, since the rate of such a process should be slowed by electron-withdrawing groups.The ketones, however, react much more rapidly than benzylcyclopropane, a model for the direct protonation mechanism.The homoconjugate mechanism involves rapid protonation of the side chain, followed by nucleophilic attack on the cyclopropane ring.The reaction is limited to substrates that can be protonated on the side chain to produce an intermediate with charge ajacent to the cyclopropane ring.This charge must be able to be transmitted by resonance to the unsubstituted ring positions in order to facilitate the nucleophilic step.
- Lambert, Joseph B.,Napoli, James J.,Johnson, Katharine Kappauf,Taba, Kalulu N.,Packard, Beverly Sue
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p. 1291 - 1295
(2007/10/02)
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- Nonapeptide and decapeptide analogs of LHRH, useful as LHRH agonist
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Synthetic nonapeptide and decapeptide LHRH agonists analogs having a novel gaunadino-substituted, amidine, tertiary or quatrinary aminoacyl residue at position 6 are disclosed herein.
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- Organic compounds substituted heptadeca-5,9- and 5,10-dienoic acid
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The present invention provides novel substituted heptadeca-5,9- and 5,10-dienoic acid and similar fatty acid compounds which are derivatives of certain prostaglandins and are potent thromboxane A2 inhibitors. By virtue of this pharmacological property, they represent useful pharmacological agents for a wide variety of purposes.
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- Nonapeptide and decapeptide analogs of LHRH, useful as LHRH antagonists
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Nonapeptide and decapeptide analogs of LHRH which have the formula: STR1 and the pharmaceutically acceptable salts thereof, wherein: X is a D-alanyl residue wherein one hydrogen on C-3 is replaced by:(a) a carbocyclic aryl-containing radical selected from the group consisting of phenyl substituted with three or more straight chain lower alkyl groups, naphthyl, anthryl, fluorenyl, phenanthryl, biphenylyl and benzhydryl; or(b) a saturated carbocyclic radical selected from the group consisting of cyclohexyl substituted with three or more straight chain lower alkyl groups, perhydronaphthyl, perhydrobiphenylyl, perhydro-2,2-diphenylmethyl, and adamantyl; or(c) a heterocyclic aryl containing radical selected from the group consisting of radicals represented by the following structural formulas: STR2 wherein A"" and A'' are independently selected from the group consisting of hydrogen, lower alkyl, chlorine, and bromine, and G is selected from the group consisting of oxygen, nitrogen, and sulfur;A is an aminoacyl residue selected from the group consisting of L-pyroglutamyl, D-pyroglutamyl, N-acyl-L-prolyl, N-acyl-D-prolyl, N-acyl-D-tryptophanyl, N-acyl-D-phenylalanyl, N-acyl-D-p-halophenylalanyl, and N-acyl-X wherein X is as defined previously;B is an amino acyl residue selected from the group consisting of D-phenylalanyl, D-p-halophenylalanyl, 2,2-diphenylglycyl, and X wherein X is as defined previously;C is an amino acyl residue selected from the group consisting of L-tryptophanyl, D-tryptophanyl, D-phenylalanyl and X wherein X is as defined above;E is glycinamide or --NH--R 1, wherein R 1 is lower alkyl, cycloalkyl, fluoro lower alkyl or STR3 wherein R 2 is hydrogen or lower alkyl; are disclosed. These compounds are LHRH antagonists.
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- Nonapeptide and decapeptide agonists of luteinizing hormone releasing hormone containing heterocyclic amino acid residues
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Nonapeptide and decapeptide analogs of LH-RH of the formula STR1 and the pharmaceutically acceptable salts thereof wherein: V is tryptophyl, phenylalanyl or 3-(1-naphthyl)-L-alanyl; W is tyrosyl, phenylalanyl or 3-(1-pentafluorophenyl)-L-alanyl; X is a D-amino acid residue of the formula: STR2 wherein R is a heterocyclic aryl containing radical selected from the group consisting of radicals represented by the following structural formulas: STR3 wherein A and A' are independently selected from the group consisting of hydrogen, lower alkyl, chlorine, and bromine, and G is selected from the group consisting of oxygen, nitrogen, and sulfur; Y is leucyl, isoleucyl, nor-leucyl or N-methyl-leucyl; Z is glycinamide or --NH--R1, wherein: R1 is lower alkyl, cycloalkyl, fluoro lower alkyl or STR4 wherein R2 is hydrogen or lower alkyl, are disclosed. These compounds exhibit potent LH-RH agonist properties.
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- Nonapeptide and decapeptide derivatives of luteinizing hormone releasing hormone
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Nonapeptide and decapeptide analogs of LH-RH of the formula and the pharmaceutically acceptable salts thereof wherein: V is tryptophyl, phenylalanyl or 3-(1-naphthyl)-L-alanyl; W is tyrosyl, phenylalanyl or 3-(1-pentafluorophenyl)-L-alanyl; X is a D-amino acid residue STR1 wherein R is (a) a carbocyclic aryl-containing radical selected from the group consisting of naphthyl, anthryl, fluorenyl, phenanthryl, biphenylyl, benzhydryl and phenyl substituted with three or more straight chain lower alkyl groups; or (b) a saturated carbocyclic radical selected from the group consisting of cyclohexyl substituted with three or more straight chain lower alkyl groups, perhydronaphthyl, perhydrobiphenylyl, perhydro-2,2-diphenylmethyl and adamantyl; Y is leucyl, isoleucyl, nor-leucyl or N-methyl-leucyl; Z is glycinamide or --NH--R1, wherein R1 is lower alkyl, cycloalkyl, fluoro lower alkyl or STR2 wherein R2 is hydrogen or lower alkyl, are disclosed. These compounds exhibit potent LH-RH agonist properties.
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