- Preparation method of 2-bromo-3-methoxypyridine
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The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of 2-bromine-3-methoxypyridine, which comprises the following reaction steps: (1) preparation of 2-bromine-3-hydroxypyridine, and (2) preparation of 2-bromine-3-methoxypyridine: cooling the sodium hydroxide aqueous solution to -10 DEG C to 0 DEG C by using an ice salt bath, and dropwise adding liquid bromine within the temperature range, dissolving 3-hydroxypyridine in a sodium hydroxide aqueous solution, dropwise adding the solution into the liquid bromine solution, and keepingthe system temperature at 10-15 DEG C, after dropwise adding, stirring the mixed solution for 2.5-3 hours at room temperature, and then adjusting the pH value to 7 by using acid; and recrystallizing the obtained crude product to obtain the 2-bromo-3-hydroxypyridine. The method has the beneficial effects of mild reaction conditions, short route and high yield.
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Paragraph 0014-0015; 0017-0018; 0021-0022
(2020/02/14)
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- A 2 - bromo -3 - methoxy pyridine preparation method
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The invention belongs to the field of organic synthetic technology, in particular to a 2 - bromo - 3 - methoxy pyridine of the preparation method, the reaction steps are as follows: (1) 2 - bromo - 3 - hydroxy pyridine, (2) 2 - bromo - 3 - methoxy pyridine; ice salt bath for the aqueous sodium hydroxide solution cooled to - 10 - 0 °C, in this temperature range, [...]; the 3 - hydroxy pyridine dissolved in the sodium hydroxide solution, then the solution is dropped to the above bromine solution, to maintain the system temperature is 10 - 15 °C; drops, room temperature stirring 2.5 - 3 hours, then use acid to adjust pH to 7; the resulting crude product recrystallized, to 2 - bromo - 3 - hydroxy pyridine. The beneficial effect of the invention is: mild reaction conditions, route is short, high yield.
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Paragraph 0014; 0015; 0017; 0018; 0021; 0022
(2019/05/28)
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- Identification of 4-(4-nitro-2-phenethoxyphenyl)pyridine as a promising new lead for discovering inhibitors of both human and rat 11β-Hydroxylase
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The inhibition of 11β-hydroxylase is a promising strategy for the treatment of Cushing's syndrome, in particular for the recurrent and subclinical cases. To achieve proof of concept in rats, efforts were paid to identify novel lead compounds inhibiting both human and rat CYP11B1. Modifications on a potent promiscuous inhibitor of hCYP11B1, hCYP11B2 and hCYP19 (compound IV) that exhibited moderate rCYP11B1 inhibition led to compound 8 as a new promising lead compound. Significant improvements compared to starting point IV were achieved regarding inhibitory potency against both human and rat CYP11B1 (IC50 values of 2 and 163 nM, respectively) as well as selectivity over hCYP19 (IC50 Combining double low line 1900 nM). Accordingly, compound 8 was around 7-and 28-fold more potent than metyrapone regarding the inhibition of human and rat CYP11B1 and exhibited a comparable selectivity over hCYP11B2 (SF of 3.5 vs 4.9). With further optimizations on this new lead compound 8, drug candidates with satisfying profiles are expected to be discovered.
- Hu, Qingzhong,Kunde, Jessica,Hanke, Nina,Hartmann, Rolf W.
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supporting information
p. 139 - 150
(2015/04/22)
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- 5-HT RECEPTOR MODULATORS
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The invention relates to compounds of formula (I), useful for treating disorders mediated by the 5-hydroxytryptamine (serotonin) receptor IB (5-HT1B), e.g. vascular disorders, cancer and CNS disorders. The invention also provides methods of treating such disorders, and compounds and compositions etc. for their treatment.
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Paragraph 0594; 0595; 0596
(2013/03/26)
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- Synthesis of the phenylpyridal scaffold as a helical peptide mimetic
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Phenylpyridal- and phenyldipyridal-based scaffolds have been designed and synthesized as novel helical peptide mimetics. The synthesis required optimisation and selective alkylation in producing 2,6-functionalized 3-hydroxypyridine derivatives for a convergent scheme. The pyridine analogues were coupled by a series of Suzuki/Stille types cross-coupling reactions. A series of biaryl and ter-aryl substituted heterocycles were produced. The synthetic approach was concise and high yielding allowing large variability at the wanted sidechain attachment points. A number of compounds were synthesised to show the versatility of the strategy.
- Bourne, Gregory T.,Kuster, Daniel J.,Marshall, Garland R.
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supporting information; experimental part
p. 8439 - 8445
(2010/09/08)
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- Mild cleavage of aryl mesylates: Methanesulfonate as potent protecting group for phenols
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A mild protocol for the chemoselective deprotection of aryl methanesulfonates is described. The transformation can be conducted on highly functionalized substrates and renders the methanesulfonate a useful, previously underutilized protecting group for phenols.
- Ritter, Tobias,Stanek, Kyrill,Larrosa, Igor,Carreira, Erick M.
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p. 1513 - 1514
(2007/10/03)
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- Quinuclidines-substituted-multi-cyclic-heteroaryls for the treatment of disease
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The invention provides compounds of Formula I: 1where in W is 2These compounds may be in the form of pharmaceutical salts or compositions, racemic mixtures, or pure enantiomers thereof. The compounds of Formula I are useful to treat diseases or conditions in which α7 is known to be involved.
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- Mild regioselective halogenation of activated pyridines with N-bromosuccinimide
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Regioselective mono and dihalogenations of amino, hydroxy and methoxy pyridines (2-, 3-, and 4-substituted) as well as 2,6-dimethoxy pyridine with N-bromosuccinimide in different solvents have been studied. Reactivity of the substrates decreases in the order amino>hydroxy>methoxy and regioselectivity depends on the position of the substituent (2-substituted > 3-substituted). In most of the cases we obtained monobrominated derivatives regioselectively and in high yields. Hydroxy and amino pyridines can also be dibrominated in almost quantitative yield with 2 equivalents of NBS.
- Canibano,Rodriguez,Santos,Sanz-Tejedor,Carreno,Gonzalez,Garcia-Ruano
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p. 2175 - 2179
(2007/10/03)
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- Certain 3-hydroxy-6-hydroxymethyl-pyridine intermediates
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The compounds of the invention are tri-substituted pyridine intermediates, useful in the preparation of final products, wherein said final products are involved in the preparation of medicaments. Said medicaments are useful for the treatment of various diseases including psoriasis. A compound of the formula (II): STR1 wherein R1 is hydrogen, benzyl or a group of the formula (A): STR2 in which n is 1 to 20; and R5 is hydrogen, C1-6 alkyl, C1-6 alkoxy or trifluoromethyl; and R7 is a leaving group consisting of halogen, OTf or (Trifluorate, e.g. OSO2 CF3), OSO2 alkyl and OSO2 Ar wherein Ar represents optionally substituted aryl.
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- Palladium catalyzed vinylic substitution reactions with 2-substituted-pyridines
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This invention involves a coupling reaction involving an organo-metallic catalyst, preferably a palladium catalyst involving reacting 2-halo-3-hydroxy-6-hydroxymethylpyridine, acrylic acid or its alkali metal salt and benzyl or a phenylalkyl derivative in presence of a dipolar aprotic solvent producing none other than the expected 2-propenoate-3-benzyl or phenylalkylether-6-hydroxymethyl-pyridine product. Said products are converted into medicaments useful for treating psoriasis.
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- Synthesis of Orelline
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Orelline (1), a metabolite of the toadstool Cortinarius Orellanus Fries with 2,2'-bipyridine structure, has been synthesized by the following method.The easily accessible 2-bromo-3-hydroxypyridine (3) was converted into the corresponding methyl (SEM) ether 4 and coupled with Zn and NiCl2/Ph3P to form the bipyridine derivative 5 in 79percent yield.Due to the chelating effect of the two SEM-ether groups in 5, it was possible to form selectively the dilithium compound 6 by an exchange reaction with BuLi at -50 deg C in Et2O.Reaction of 6 with electrophiles at -20 deg C afforded the 4- and 4,4'-substituted bipyridines 7-14 in excellent-to-reasonable yield.Oxidations of 6 with 2-(phenylsulfonyl)-3-phenyloxaziridin and with bis(trimethylsilyl)peroxide gave the 4,4'-diol 9 in 22 and 10percent yield, respectively.Methanolysis of 9 directly afforded crystalline 1 in high yield, with properties identical with those of natural orelline.Formylation of 6 with N-formylmorpholine gave 45percent of the dicarbaldehyde 13.Removal of the SEM groups in 13 by hydrolysis afforded the dihydroxydicarbaldehyde 15 that could be oxidized to 1 with alkaline H2O2.Attempts to oxidize 1 to orellanine (2) with 35percent H2O2 according to a known procedure were unsuccessful (cf.Exper.Part).Compound 7 with two Me3Si groups in 4,4'-position gave after methanolysis the fluorescence dye 16 with an appreciable Stokes shift in cyclohexane.
- Hasseberg, Hans-Albrecht,Gerlach, Hans
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p. 957 - 963
(2007/10/02)
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- Synthetic Uses of the Sequential Ring Positional Reactivity in Pyridin-3-ol and Derivatives
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A series of ring-substituted pyridin-3-ols has been prepared.The key to the scheme is the introduction of a bromo group to a specific ring position as a temporary blocking agent.As well as hydrogenolysis of the bromo function, nucleophilic displacement has also been investigated.
- Clark, Gary J.,Deady, Leslie W.
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p. 927 - 932
(2007/10/02)
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