- Preparation method of 3-nitro-4-benzyloxy-2-bromoacetophenone
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The invention relates to a preparation method of 3-nitro-4-benzyloxy-2-bromoacetophenone. Particularly, 3-nitro-4-hydroxyacetophenone and benzyl bromide are taken as raw materials, and 3-nitro-4-benzyloxy-2-bromoacetophenone is synthesized through hydroxy protection and trimethylphenylammonium tribromide bromination reaction in a high-yield manner. The preparation method of 3-nitro-4-benzyloxy-2-bromoacetophenone in the synthesis route is high in yield, low in cost, easy to operate and suitable for industrialization.
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Paragraph 0016; 0020
(2018/09/08)
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- Benzylether fumaric acid luck not Trow an important intermediate for the synthesis of compound
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The invention discloses a synthetic method of a formoterol fumarate important intermediate benzyl ether compound. The synthetic method comprises the following steps: enabling a compound I to react with a compound II in an organic solvent at 100-120 DEG C for 4-6 hours under the concerted catalysis of a catalyst (I) and a catalyst (II); and by using an inorganic alkaline substance as an acid-binding agent in the reaction process, after the reaction ends, adding water to perform cooling and crystallization, and filtering to obtain the benzyl ether compound. The synthetic steps disclosed by the invention perform concerted catalysis on benzyl etherification reaction between a substitute and benzyl chloride by adopting the two catalysts at the same time, and can be used for increasing the reaction speed, shortening the reaction time, shortening the total reaction time to 4 hours from 48 hours, and greatly improving the production efficiency; and after the reaction ends, the qualified benzyl ether compound (of which the content is more than 98%) can be obtained without refining; the synthetic method disclosed by the invention is more suitable for the large-scale industrial production of formoterol fumarate.
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Paragraph 0059; 0062
(2017/01/23)
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- Design, synthesis and evaluation of dual pharmacology β2- adrenoceptor agonists and PDE4 inhibitors
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A novel series of formoterol-phthalazinone hybrids were synthesised and evaluated as dual pharmacology β2-adrenoceptor agonists and PDE4 inhibitors. Most of the hybrids displayed high β2-adrenoceptor agonist and moderate PDE4 inhibitory activities. The most potent compound, (R,R)-11c, exhibited agonist (EC50 = 1.05 nM, pEC50 = 9.0) and potent PDE4B2 inhibitory activities (IC50 = 0.092 μM).
- Huang, Ling,Shan, Wenjun,Zhou, Qi,Xie, Jiaxing,Lai, Kefang,Li, Xingshu
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p. 249 - 253
(2014/01/17)
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- Dual β2-adrenoceptor agonists-PDE4 inhibitors for the treatment of asthma and COPD
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We designed and synthesized a novel class of dual pharmacology bronchodilators targeting both b2-adrenoceptor and PDE4 by applying a multivalent approach. The most potent dual pharmacology molecule, compound 29, possessed good inhibitory activity on PDE4B2 (IC50 = 0.278 μM, which was more potent than phthalazinone, IC50 = 0.520 lM) and possessed excellent relaxant effects on tracheal rings precontracted by histamine (pEC50 = 9.3).
- Shan, Wen-Jun,Huang, Ling,Zhou, Qi,Jiang, Huai-Lei,Luo, Zong-Hua,Lai, Ke-Fang,Li, Xing-Shu
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supporting information; experimental part
p. 1523 - 1526
(2012/04/04)
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- P-Hydroxyphenacyl photoremovable protecting groups Robust photochemistry despite substituent diversity
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A broadly based investigation of the effects of a diverse array of substituents on the photochemical rearrangement of p-hydroxyphenacyl esters has demonstrated that common substituents such as F, MeO, CN, CO2R, CONH2, and CH3 have little effect on the rate and quantum efficiencies for the photo-Favorskii rearrangement and the release of the acid leaving group or on the lifetimes of the reactive triplet state. A decrease in the quantum yields across all substituents was observed for the release and rearrangement when the photolyses were carried out in buffered aqueous media at pHs that exceeded the ground-state pKa of the chromophore where the conjugate base is the predominant form. Otherwise, substituents have only a very modest effect on the photoreaction of these robust chromophores.
- Givens, Richard S.,Stensrud, Kenneth,Conrad, Peter G.,Yousef, Abraham L.,Perera, Chamani,Senadheera, Sanjeewa N.,Heger, Dominik,Wirz, Jakob
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scheme or table
p. 364 - 384
(2011/06/22)
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- Development of an enabling route to PF-00610355: A novel inhaled β2-adrenoreceptor agonist
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The initial route used to prepare PF-00610355 (8) for early clinical development is described. Through careful choice of solvent, an efficient, telescoped route to carboxylic acid 23 was developed, affording this late-stage intermediate in 80% yield over 4 steps. Deprotection of 23 to give sodium salt 24a and coupling with amine 6·HCl afforded the desired API. Effective synthetic routes to two of the starting materials, chiral bromide 1 and amine 6, are also described.
- De Koning, Pieter D.,Gladwell, Iain R.,Moses, Ian B.,Panesar, Maninder S.,Pettman, Alan J.,Thomson, Nicholas M.
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experimental part
p. 1247 - 1255
(2012/01/19)
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- The asymmetric synthesis of (R,R)-formoterol via transfer hydrogenation with polyethylene glycol bound Rh catalyst in PEG2000 and water
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(R,R)-formoterol was synthesized in seven steps with 4-hydroxyl-3-nitro- acetophenone as the starting material. The key intermediate, the chiral secondary alcohol 4, was prepared via Rh-catalyzed asymmetric transfer hydrogenation with (S,S)-PEGBsDPEN as the ligand and sodium formate as the hydrogen donor under mild conditions. With a mixture of PEG 2000 and water as the reaction media, the catalyst system could be recycled four times.
- Huang, Ling,Liu, Juntao,Shan, Wenjun,Liu, Bao,Shi, Anding,Li, Xingshu
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experimental part
p. 206 - 211
(2010/11/18)
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- PHENYL SUBSTITUTED PYRAZINOYLGUANIDINE SODIUM CHANNEL BLOCKERS POSSESSING BETA AGONIST ACTIVITY
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The present invention relates to sodium channel blockers. The present invention also includes a variety of methods of treatment using these inventive sodium channel blockers.
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Page/Page column 41; 69
(2008/06/13)
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- ALIPHATIC PYRAZINOYLGUANIDINE SODIUM CHANNEL BLOCKERS WITH BETA AGONIST ACTIVITY
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The present invention provides sodium channel blockers possessing beta-adrenergic receptor agonist activity.
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Page/Page column 51
(2010/11/29)
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- An efficient enantioselective synthesis of (R,R)-formoterol, a potent bronchodilator, using lipases
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The potent β2-adrenergic receptor agonist formoterol (R,R)-1 has been obtained in enantiomerically pure form by a convenient chemoenzymatic approach by coupling of epoxide (R)-6 with the unprotected primary amine (R)-9. Both chiral precursors have been prepared by enantiodifferentiation processes involving Pseudomonas cepacia (lipase PS) and Candida antarctica lipase (CALB), respectively. For the resolution of amine 9, we have found that utilization of triethylamine as non-reactive base enhances the reaction rate and the enantioselectivity of the process. The key coupling reaction of (R)-6 and (R)-9 has been conducted through derivatization of the amine with the labile trimethylsilyl group, which liberates the amino group of the resulting amino alcohol (R,R)-11 upon column chromatography purification. In this way, the overall approach is shorter than others previously described. Copyright (C) 2000 Elsevier Science Ltd.
- Campos, Francisco,Bosch, M. Pilar,Guerrero, Angel
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p. 2705 - 2717
(2007/10/03)
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- Desformoterol and process for its preparation
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The (R,R)-, (S,S)-, (R,S)-, (R,S)- isomers of 3-amino-4-hydroxy-α-[[[2-(4-methoxyphenyl)-1-methylethyl]amino]methyl]-benzenemethanol (D) STR1 are disclosed, as well as an efficient method for their stereoselective synthesis. A method and composition are also disclosed utilizing desformoterol (D) as a bronchodilator, having high selectivity for β2 receptors.
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- An Intermediate in the Synthesis of Formoterol
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In the title compound, 4-benzyloxy-3-nitrophenacyl bromide, C15H12BrNO4, the two planar nitrophenyl and benzyloxy groups are inclined at a dihedral angle of 17.1(1) deg.The NO2 group is twisted out of the plane of the phenyl ring by 20.4(3) deg to minimize steric hindrance between O(4) and O(3); the O(4)...O(3) separation is 2.600(5) Angstroem and the angle O(4)...O(3)-N(1) is 88.2(4) deg.
- Mohan, K. Chandra,Ravikumar, K.,Vittal, T. V. S. K.,Gido, C. K.
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p. 627 - 629
(2007/10/02)
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- 2-(3-Benzyloxy-4-nitrophenyl)oxirane, an Intermediate in the Synthesis of Formoterol
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In the title compound, C15H13NO4, the two planar nitrophenyl and benzyloxy groups are inclined at 152.3(2) deg.The torsion angle about the central C-O bond is 177.5(5) deg, giving an extended C-C-O-C chain.The nitro group is twisted out of the plane of the phenyl ring by 28.4(3) deg to diminish steric hindrance; O atoms of the nitro and benzyloxy groups are separated by only 2.625(7) Angstroem.The dihedral angles between the epoxy ring and the two aromatic rings are 98.3(3) and 102.6(3) deg.There is a possible C-H...O intermolecular interaction.
- Mohan, K. Chandra,Ravikumar, K.,Vittal, T. V. S. K.,Gido, C. K.
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p. 1294 - 1295
(2007/10/02)
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