18856-69-4

Upstream product

• 22398-14-7 dimethyl (methoxymethylene)malonate 
• 124-40-3 dimethyl amine 
• 75039-60-0 5-[(dimethylamino)methylene]-2,2-dimethyl-1,3-dioxane-4,6-dione 
• 74-88-4 methyl iodide 
• 4637-24-5 N,N-dimethyl-formamide dimethyl acetal 
• 108-59-8 malonic acid dimethyl ester 
• 68-12-2 N,N-dimethyl-formamide 

Downstream Products

• 1275588-51-6 dimethyl 2-((benzylamino)methylene)malonate 

Relevant academic research and scientific papers

Conformational studies of aminomethylene-malonic acid dimethylester and its N-methyl derivatives using vibrational spectroscopy, X-ray analysis and ab initio calculations

The IR and Raman spectra of aminomethylene-malonic acid dimethylester (AMDME) [NH2{single bond}CH{double bond, long}C(COOCH3)2] and its N-methyl derivatives (MAMDME and DMAMDME) were measured in solid phase and in different solvents at various temperatures. X-ray analysis revealed that AMDME exists in solid phase as EZ conformer, MAMDME as ZZa conformer and DMAMDME as ZE conformer (the first and second E or Z letters express the orientation of the carbonyl oxygen to the C{double bond, long}C double bond for trans and cis methylester group, respectively, and the third letter a denotes anti position of methylamino group with respect to the C{double bond, long}C double bond). In less polar solutions dominantly two ZZ and EZ conformational forms of AMDME and ZZa and EZa of MAMDME are observed, whereas in more polar environments a third conformational form (ZE and ZEa, respectively) also appeared. The behaviour of DMAMDME is different because there is no intramolecular hydrogen bond and in less polar solutions exists in two ZZ and ZE conformational forms. Very weak indications of a third conformational form (probably EZ conformer) were observed only in more polar surroundings. From the solution IR temperature dependent spectra the energy difference between ZE and ZZ conformers of ΔH = 1.8 ± 0.5 kJ mol-1 in chloroform and ΔH = 4.2 ± 0.5 kJ mol-1 in acetonitrile was estimated with the ZZ one being more stable. The geometries and relative energies of the possible conformers of all three compounds were evaluated using ab initio MP2 and DFT B3LYP methods in 6-31G** basis set with PCM solvent effect inclusion. The influence of environment polarity on the conformational equilibrium is discussed.

Preparation method of pyrazole type herbicide intermediate 1-methyl-5-hydroxypyrazole

The invention belongs to the technical field of preparation of pyrazole type herbicide intermediates, and particularly relates to a preparation method of a pyrazole type herbicide intermediate 1-methyl-5-hydroxypyrazole. The preparation method of the 1-methyl-5-hydroxypyrazole comprises the following steps: (1) in the presence of alkali, enabling dimethyl malonate of a compound (1) to react with aformamide compound and an alkylation reagent in a solvent to generate a compound (2); and (2) carrying out cyclization reaction on the obtained compound (2) and methylhydrazine/hydrazine hydrate in asolvent, and carrying out hydrolysis and decarboxylation by using an acid to obtain a compound (3). According to the method, DMF, an alkylation reagent and the compound (1) react to obtain the compound (2), the obtained compound (2) is good in selectivity when being subjected to ring-closure reaction with methylhydrazine (or hydrazine hydrate), and a target product compound (3) with higher yieldand purity can be obtained. Moreover, the raw materials used in the synthesis method disclosed by the invention are relatively weak in corrosivity, easy to recover and relatively low in price, so thatindustrial production is facilitated.

Synthesis method of 2-(aminomethyl)-N1,N1-dimethylpropane-1,3-diamine trihydrochloride

The invention provides a synthesis method of 2-(aminomethyl)-N1,N1-dimethylpropane-1,3-diamine trihydrochloride. The synthesis method comprises the following steps: S1, reacting malonic acid dicarboxylic acid with DMF-DMA to generate an intermediate 1; S2

SUBSTITUTED BICYCLE HETEROCYCLIC DERIVATIVES USEFUL AS ROMK CHANNEL INHIBITORS

Disclosed are compounds of Formula (I) or a salt thereof, wherein R1 is (II) or (III); each W is independently NR1b or O; Z is a bond or CHR1d; and R1, R2, Rd, R3, L1, L2, R1a, R1b, R1c, and n are define herein. Also disclosed are methods of using such compounds as inhibitors of ROMK, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating cardiovascular diseases.

SUBSTITUTED NITROGEN CONTAINING COMPOUNDS

Disclosed are compounds of Formula (I): or a salt thereof, Formula (II) wherein R1 is: or; each W is independently NR1b or O; Z is a bond or CHR1d; and R1, R2, Rd, R3a, R3b, L1, B, V, Y, and n are defined herein. Also disclosed are methods of using such compounds as inhibitors of ROMK, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating cardiovascular diseases.

Preparation method of novel isoquinoline medicine molecule with antibacterial activity

The invention discloses a preparation method of a novel isoquinoline medicine molecule with antibacterial activity and belongs to the technical field of synthesis of medicines. The key points of the technical scheme are characterized in that formulas are

Regioselective synthesis of 1- and 4-substituted 7-oxopyrazolo[1,5-a]pyrimidine-3-carboxamides

The synthesis of 7-substituted pyrazolo[1,5-a]pyrimidine-3-carboxamides was studied. First, methyl 7-hydroxypyrazolo[1,5-a]pyrimidine-3-carboxylate (5) was prepared in three steps from methyl 5-amino-1H-pyrazole-4-carboxylate (3). Treatment of 5 with POCl3 gave the highly reactive 7-chloro derivative 10, which was reacted with amines, benzyl alcohol, and phenylboronic acid in the presence of Pd-catalyst to give the corresponding 7-substituted derivatives 11. Hydrolysis of the esters 5 and 11 followed by amidation gave the corresponding carboxamides 16a-h and 15. Regioselectivity of N-alkylation of 7-hydroxypyrazolo[1,5-a]pyrimidine-3-carboxylic acid derivatives 5 and 16 was tunable by the carboxy function. Alkylation of the secondary amides 16a-f furnished the 1-alkyl derivatives 17a-f, whereas the ester 5 and the tertiary amides 16g,h gave the 4-alkyl derivatives 14a-d and 16m,n, selectively.

The synthesis of ethyl (Z)-2-[2,2-bis(methoxycarbonyl)-ethenyl]aimno-3-dimethylaminopropenoate and its application to the synthesis of fused aminopyrimidinones and aminopyranones+

Ethyl (Z)-2-[2,2-bis(methoxycarbonyl)ethenyl]amino-3-dimethylaminopropenoate (4) was prepared in three steps from dimethyl malonate, and used as a reagent for the preparation of' N-protected 6-amino-5H-thiazolo[3,2-a]pyrimidin-4-one 5a and its benzo analogue 6a, 3-amino-4H-pyrido[1,2-a]pyrimidin-4-ones 7a-9a, 3-amino-2H,5H-pyrano[3,2-c]pyran-2-one 10a and its benzo analogue 11a, 3-amino-2H-1-benzopyran-2-one derivative 12a and 3-amino-4H-quinolizin-4-one derivative 13a. Free amino heterocyclic compounds 5b-9b were prepared from 5a-9a by removal of the 2,2-bis(methoxycarbonyl)ethenyl group as N-protecting group by heating with hydrazine hydrate.

Process for the preparation of aminomethylene compounds

Aminomethylene compounds of the formula STR1 may advantageously be prepared by reacting C--H-acidic compounds of the formula STR2 with formamide acetals of the formula STR3 in which the radicals R1 to R6 have the meaning given in the description, if the process is carried out in the presence of a secondary amine of the formula STR4 in which R7 and R8 have the meaning given in the description.

Process for the preparation of aminomethylene compounds

Aminomethylene compounds of the formula STR1 can be prepared by reaction of C-H-acid compounds of the formula STR2 with salts of the formula STR3 in the presence of simple inorganic bases, where the radicals R1 to R4, R7, R8 and X? have the meanings given in the description.