33641-15-5Relevant articles and documents
Preparation method of pyrazole type herbicide intermediate 1-methyl-5-hydroxypyrazole
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Paragraph 0035; 0038-0040; 0043-0045; 0048-0049, (2021/03/31)
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 1-methyl-5-hydroxy pyrazole
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Paragraph 0014; 0030-0046, (2021/03/13)
The invention relates to a synthesis method of 1-methyl-5-hydroxy pyrazole, which comprises the following steps of dropwisely adding tetrahydropyrrole into diethyl ethoxymethylene malonate at room temperature, and reacting at 15-80 DEG C for 2-6 hours to obtain a reaction solution A containing a compound represented by a formula (II), dropwise adding a methylhydrazine aqueous solution into the reaction solution A, and reacting at 15-80 DEG C for 2-6 hours to obtain a reaction solution B containing a compound shown as a formula (III), dropwise adding an acidic solution into the reaction solution B, and heating and refluxing for 4-8 hours at 90-120 DEG C after dropwise adding to obtain a reaction solution C containing a compound shown as a formula (IV), and carrying out post-treatment on thereaction solution C to obtain the target compound 1-methyl-5-hydroxy pyrazole. The synthesis method has the advantages of higher activity, higher reaction rate, better selectivity, higher total yield, cheap and accessible raw materials and simple post-treatment, and can obtain the solid 1-methyl-5-hydroxy pyrazole with higher purity.
Flexible analogues of WAY-267,464: Synthesis and pharmacology at the human oxytocin and vasopressin 1a receptors
Jorgensen, William T.,Gulliver, Damien W.,Werry, Eryn L.,Reekie, Tristan,Connor, Mark,Kassiou, Michael
, p. 730 - 740 (2016/01/09)
A previously identified, non-peptidic oxytocin (OT) receptor agonist WAY-267,464 (1) and nine novel derivatives (3, 4a-7a, 4b-7b) were synthesised and evaluated in vitro with the aim of systematically exploring hydrogen bonding interactions and ligand flexibility. All analogues were subjected to competition radioligand binding assays at human oxytocin (OT) and arginine vasopressin 1a (V1a) receptors. Physiological activity was determined using whole cell IP1 accumulation assays. Under these conditions, WAY-267,464 had higher affinity for the V1a receptor compared to the OT receptor (8.5x more selective) with poor functional selectivity (2x selective for OT receptor agonism over V1a receptor antagonism). Methylation of the resorcinol moiety (3) reversed the OT receptor pharmacological profile, removing agonist activity and inducing antagonist activity, without altering V1a receptor pharmacology. All flexible tethered derivatives removed OT receptor affinity and activity resulting in the generation of highly selective V1a receptor ligands.