- A direct and high yielding route to 2-(5-tetrazolyl) substituted benzopyran-4-ones: Synthesis of pranlukast
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A direct and high yielding route to 2-(5-tetrazolyl)benzopyran-4-ones 1, including pranlukast 1a is described. This involves the Claisen condensation reaction between the relevant hydroxyacetophenone 2 and the ethyl ester of tetrazole-2-carboxylic acid 5 to give the 1,3-diketone 6, which is then cyclised to give the desired benzopyran-4-ones 1.
- Geen, Graham R.,Giles, Robert G.,Grinter, Trevor J.,Hayler, John D.,Howie, Simon L. B.,Johnson, Graham,Mann, Inderjit S.,Novack, Vance J.,Oxley, Paul W.,Quick, John K.,Smith, Neil
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- Industrial preparation method of anti-asthma drug pranlukast intermediate
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The invention discloses a preparation method of a pranlukast intermediate N-(2-cyano-4-oxo-4H-chromene-8-yl)-4-(4-butoxyphenyl)benzamide (short for formula I), specifically a method for preparing N-(2-cyano-4-oxo-4H-chromene-8-yl)-4-(4-butoxyphenyl)benzamide by carrying out a dewatering reaction on 4-oxo-8-[4-(4-butoxyphenyl)benzamide]-4H-chromene-2-formamide (short for formula II). The preparation method of the pranlukast intermediate represented by the formula I is high in yield, good in product color, high in product purity and beneficial to industrial production.
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Paragraph 0021; 0023; 0024
(2020/04/17)
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- Preparation method for pranlukast
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The invention belongs to the field of medicines and especially relates to a preparation method for pranlukast. The method comprises the following steps: A) adding 4-bromobenzoic acid and thionyl chloride into a solvent and reacting, thereby acquiring 4-bromo-benzoyl chloride; B) adding the 4-bromo-benzoyl chloride acquired in the step A), alkali and 3-amino-2-ethyl iodobenzoate into the solvent and reacting, thereby acquiring 2-iodine-3-(4-bromobenzamide) ethyl benzoate; C) adding the 2-iodine-3-(4-bromobenzamide) ethyl benzoate acquired in the step B), alkali and 1-(1H-tetrazole-5-group) aceton into the solvent and reacting, thereby acquiring 4-bromine-N-(4-oxo-2-(1H-tetrazole-5-group)-4H-benzopyrone-8-group) benzamide; D) adding the 4-bromine-N-(4-oxo-2-(1H-tetrazole-5-group)-4H-benzopyrone-8-group) benzamide acquired in the step C), catalyst and alkali into the solvent and reacting, thereby acquiring the product. The method provided by the invention is simple and practicable in process, low in production cost and high in yield.
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- Novel method for preparing high-purity asthma treatment drug pranlukast
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The invention discloses a novel method for preparing a high-purity asthma treatment drug pranlukast, and relates to the technical field of organic synthesis of drugs. The method comprises the following steps: carrying out neutralization and a salt forming reaction on a reaction raw material 8-amino-4-oxo-2-tetrazole-5-yl-4H-1-benzopyran hydrochloride and an alkaline substance to generate an intermediate, and carrying out an amidation reaction on the obtained intermediate and p-phenylbutoxybenzoyl chloride in a non-polar solvent to prepare the pranlukast. The whole process of the method is simple and clean, is easy to control, allows the purity of the obtained crude product to reach 99% or above, and allows the purity of a one-time purified product to reach 99.9% or more.
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Paragraph 0020; 0022
(2017/07/19)
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- New preparation method of Pranlukast
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The invention provides a new preparation method of drug Pranlukast for treating asthma. The new preparation method includes the specific steps that with 2-aminophenol-4-sulfonic acid as a starting material, a key intermediate 3-amino-2-hydroxyacetophenone is prepared by means of acylation, Fries rearrangement and deprotection, then reacts with 4-(phenylbutoxy)benzoic acid, and then is subjected to condensation with ethyl 1H-tetrazole-5-acetate, and finally preparation is achieved through ring closing under the acidic condition. Compared with the prior art, the raw material used for the new preparation method is low in price and easy to obtain, industrialization of a process can be achieved easily, and the obtained final product is high in purity; and no dangerous process exists, equipment is simple, and the route is novel.
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- METHOD OF REMOVING THE TRIPHENYLMETHANE PROTECTION GROUP
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The present invention relates to a method of removing triphenylmethane protection group. The method for preparing biphenyl benzoic acid derivatives of the present invention is economically advantageous and very excellent in the aspect of improving process in that: process safety is secured by using acidic ion exchange resin in the presence of organic solvent instead of using highly corrosive acid; the reaction takes much less time than do the conventional reactions which use only anhydrous methanol and few sub-reaction does occur; and the ion-exchange resin of the present invention is excellent for mass-processing because the resin can be collected and recycled only by filtration after being used.
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Page/Page column 11
(2010/07/02)
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- METHODS FOR PREPARING AMIDE DERIVATIVES
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The present invention provides a novel method for preparing an amide derivative. The method of the present invention enables to economically prepare various amide derivatives containing pranlukart by reacting a carboxylic acid derivative 5 and an amine derivative through a brief procedure compared with a conventional technology, and permits to obtain a final product at a high yield rate because it is feasible to eliminate by-products after termination of reactions. Accordingly, the present method is to be quite suitable for massive production.
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Page/Page column 17-18
(2010/04/03)
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- PROCESS FOR PREPARING SUBSTITUTED BENZOPYRAN COMPOUNDS
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The present invention relates to a novel method of synthesizing substituted benzopyran compounds, their novel intermediates and a method of their preparation thereof.
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Page/Page column 7; 14; 18
(2008/06/13)
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- Process for the production of tetrazolylbenzopyrans
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PCT No. PCT/EP97/07341 Sec. 371 Date Jul. 6, 1999 Sec. 102(e) Date Jul. 6, 1999 PCT Filed Dec. 30, 1997 PCT Pub. No. WO98/30559 PCT Pub. Date Jul. 16, 1998A process for preparing certain substituted benzopyran compounds of formula (I) is disclosed.
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- Production process and intermediate of tetrazole compound
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There are disclosed an industrially favorable process for producing a tetrazole compound of general formula (1): STR1 characterized in that a nitrile of general formula (2): is reacted with hydrazine or a salt thereof in the presence of a catalyst, followed by reaction with a nitrous acid compound of general formula (3): or a nitrile of general formula (2) is reacted with hydrogen sulfide, followed by reaction with an alkyl halide of general formula (4): with hydrazine or a salt thereof, and then with a nitrous acid compound of general formula (3); and an intermediate of general formula (5): which is useful for the production of the tetrazole compound (in which R1 to R6, A and J in the above formulas are as defined in the specification).
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- Process for preparing benzopyran compounds
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The present invention relates to a process for preparing compounds of structure (I), and the intermediate compound of formula (II).
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- Production process of 2-(tetrazol-5-yl)-4-oxo-4H-benzopyran
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There is disclosed a process for producing a 2-(tetrazol-5-yl)-4-oxo-4H-benzopyran of general formula (1): STR1 which comprises reacting a hydroxyacetophenone of general formula (2): STR2 with a tetrazole compound of general formula (3): STR3 in the presence of a base in a solvent composed mainly of at least one selected from hydrocarbons, halogenated hydrocarbons and alcohols, and then treating the reaction mixture under acidic conditions.
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- New potent antagonists of leukotrienes C4 and D4. 1. Synthesis and structure-activity relationships
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(p-Amylcinnamoyl)anthranilic acid (3a) had moderate antagonist activities against LTD4-induced smooth muscle contraction on guinea pig ileum and LTC4-induced bronchoconstriction in anesthetized guinea pigs. Modifications were made in the hydrophobic part (cinnamoyl moiety) and the hydrophilic part (anthranilate moiety) of 3a. A series of 8-(benzoylamino)-2-tetrazol-5-yl-1,4-benzodioxans and 8-(benzoylamino)-2-tetrazol-5-yl-4-oxo-4H-1-benzopyrans were revealed to be potent antagonists of leukotrienes C4 and D4. Among both series, ONO-RS-347 (18k) and ONO-RS411 (19h) were the most potent and orally active antagonists, respectively. Structure-activity relationships are discussed.
- Nakai,Konno,Kosuge,Sakuyama,Toda,Arai,Obata,Katsube,Miyamoto,Okegawa,Kawasaki
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- (FUSED) BENZ(THIO)AMIDES AND PHARMACEUTICAL USE
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A (fused) benz(thio)amide of the formula: (I) wherein B represents (i) a carbocyclic ring of from 4 to 8 members being unreplaced or replaced one, two or three of optional carbon atom(s) by oxygen, nitrogen and/or sulphur atom(s) or (ii) a divalent group of the formula: R1 represents a group of formula: (i) (ii) (iii) (iv) a straight or branched alkyl, alkenyl, or alkynyl of from 1 to 20 carbon atoms, R4 represents (i) when B represents a closed ring, a group of the formula: U(CH2)nCOOR8 (CH2)pCOOR8 or (ii) when B does not represent a ring, a group of formula: (CH2)pCOOR8 or with the proviso that compounds of formula: wherein A' is a vinylene or an ethylene group optionally substituted by straight or branched alkyl groups of from 1 to 4 carbon atom(s); R4' is -(CH2)n-COOR8 - and R1' is (i) a group of the formula: or (ii) a group of the formula: are excluded, wherein A, R2, R3, R5, R6, R7, R8, U, n, m, p, q, R5', and R6' are defined as in the above specification, possessing antagonistic activity on leukotrienes (SRS), inhibitory activity on 5 alpha -reductase, on phospholipase and on aldose reductase and being useful for the prevention and/or treatment of diseases induced by leukotrienes, 5 alpha -reductase, phospholipase and aldose reductase in mammals, especially in human beings
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