- Method of preparing medical compound stendra
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The invention discloses a method of preparing a medical compound stendra and belongs to the technical field of medical compounds. The key point of the technical scheme is as follows: the synthetic route of the method of preparing the medical compound stendra is as follows: a formula as shown in the description. The method has the advantages of being high in yield, low in cost, economical and environment-friendly, suitable for industrialization, high in product impurity and the like, and is a synthetic method which has industrial production value.
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- Preparation method of pharmaceutical compound avanafil
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The invention discloses a preparation method of a pharmaceutical compound avanafil, and belongs to the technical field of synthesis of pharmaceutical compounds. The key point of the technical scheme of the invention is as follows: a synthesis route of the synthetic method of the pharmaceutical compound avanafil is shown in the specification. The synthetic method has the advantages that the yield is high, the cost is low, the method is economical and environmentally friendly and is suitable for industrialization, the product purity is high and the like, and the method is a synthetic method withindustrial production values.
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- A pharmaceutical compound atorvastatin that non-synthetic method (by machine translation)
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The present invention discloses a pharmaceutical compound atorvastatin that non-synthetic method, which belongs to the technical field of pharmaceutical synthesis of the compounds. Technical proposal of the invention points are: a pharmaceutical compound atorvastatin that non-synthetic method, its synthetic route is: The invention has the step is short, high yield, low cost, environmentally friendly and it is suitable for industrial, purity of the product and the like, is a with the value of industrial production of synthetic method. (by machine translation)
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- Preparation method of Stendra
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The invention provides a preparation method of Stendra. The method comprises the following steps that starting materials 4-[(3-chloro-4-methoxyphenyl)methylamino]-2-[(S)-2-hydroxymethyl pyrrole-1-base]pyrimidine-5-carboxylic acid and 2-pyrimidinemethanamine are dissolved into a reactive solvent methylbenzene, a boric acid porphyrin catalyst is aded, heating and stirring are conducted to a reflux state, and the Stendra is obtained through catalysis. Accordingly, boric acid porphyrin serves as the catalyst, catalysis is conducted directly to synthesize the Stendra directly. The dosage of the catalyst is low, the reaction activity is high, operation is relatively simple, after the reaction is finished, a target product is likely to be separated from the catalyst, the difficulty of separationand purification of later products is greatly lowered, the recovered catalyst can be recycled, and the preparation cost can be significantly lowered, and the whole catalytic reaction has the advantages of being simple, environmentally friendly and the like, the input cost such as manpower and raw materials is significantly lowered, and large-scale industrial production is facilitated.
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Paragraph 0032-0058
(2019/06/07)
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- Preparation method of avanafil
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The invention provides a preparation method of avanafil, and specifically relates to the technical field of pharmaceutical chemistry. The preparation method of avanafil comprises the following steps:sequentially carrying out cyclization and chlorination reactions on methyl thiourea sulfuric acid and diethyl ethoxymethylene malonate which serve as initial raw materials to obtain 4-chloro-2-methylthiopyrimidine-5-carboxylic acid ethyl ester; then substituting and hydrolyzing with 3-chloro-4-methoxybenzylamine; condensing with 2-pyrimidinemethanamine to obtain a key intermediate, namely, 4-[(3-chloro-methoxybenzyl)amino]-2-methylthio-N-(2-pyrimidine methyl)-5-pyrimidine formamide; oxidizing the intermediate and reacting with L-prolinol to generate the avanafil. The preparation method has theadvantages of easy availability of raw materials, easiness and convenience in operation, mild reaction conditions and higher product yield.
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- Atorvastatin that non-synthetic method
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The invention provides a synthesis method of avanafil. The synthesis method of avanafil comprises the following steps: carrying out nucleophilic substitution reaction with a compound (13) or a compound (3) by a compound (18), hydrolyzing to prepare a compound (21) or a compound (22), reacting the compound (21) or the compound (22) with sulfonic acid chloride or pivaloyl chloride to obtain mixed anhydride, reacting the mixed anhydride with a compound (23) to prepare a compound (24) or a compound (25), then oxidizing the compound (24), subsequently reacting the compound (24) with a compound (9) to prepare avanafil, or directly reacting the compound (25) with the compound (9) to prepare avanafil. The synthesis method is high in controllability, simple in step, high in yield and low in cost, and is suitable for industrial production. The reaction route is shown in the description.
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- Method for preparing avanafil raw material medicine
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The invention relates to the technical field of medicine synthesis, and discloses a method for preparing an avanafil raw material medicine. The method comprises the following steps: taking a midbody -MI as an initial raw material, and performing an oxidation reaction, a condensation reaction with L-proline, a hydrolysis reaction and a dehydration condensation reaction in sequence, thereby obtaining avanafil. Aiming at the problems that a monitoring and analysis method of a conventional avanafil preparation method is not available, the invention provides a set of effective monitoring and detection method, the quality of middle products and final products can be effectively controlled, meanwhile due to adjusted purification methods of different steps, the purity of the middle products and the final products can be at a relatively high level, and the method is particularly applicable to industrial large-scale production.
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Paragraph 0047; 0072; 0073; 0074
(2017/08/28)
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- Atorvastatin that non-preparation method
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The invention relates to a preparation method of avanafil and a new compound provided in a preparation process. According to the method, 5-uracil carboxylic acid or an ester thereof is taken as the raw material, and the avanafil meeting the clinical requirements can be synthesized at a relatively cost; besides, the preparation method is simple and convenient to operate, mild in reaction conditions, high in yield, low in cost, environmentally friendly and suitable for industrial large-scale production of the avanafil.
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- A process for the preparation of atorvastatin that non-intermediate and its preparation method
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The invention provides a novel intermediate IV which is used for preparation of avanafil. The intermediate has a general formula IV as described in the specification; and in the general formula IV, R represents a C1-20 alkylsulfinyl group or a C1-20 alkylsulfonyl group. The intermediate has high purity, is suitable for industrial production and can be subjected to a one-step chemical reaction to prepare avanafil. The invention also provides a preparation method for the intermediate and a method for preparing avanafil from the intermediate.
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Paragraph 0049; 0050; 0051; 0065; 0066; 0067; 0081-0083
(2017/08/25)
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- A 4 - [(3-chloro-4-benzyl) amino] - 2 - [2 - (hydroxymethyl) - 1-pyrrolidinyl] pyrimidine-5-carboxylic acid ethyl ester preparation method
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The invention discloses a preparation method of 4-[(3-chlorine-4-methoxyl benzyl) amino]-2-[2-(hydroxymethyl)-1-pyrrolidyl]-pyrimidine-5-nonanoic acid-ethyl ester. The method comprises the following steps: dissolving 4-(3-chlorine-4-methoxyl benzyl amido)-2-methylmercapto pyrimidine-5-nonanoic acid-ethyl ester in an organic solvent; dissolving L-Prolinol in the same organic solvent; respectively controlling flow velocity to put a material liquid into a micro reactor; preheating, mixing, reacting and cooling in the micro reactor to obtain a reactant material liquid, and then discharging the reactant material liquid out of the micro reactor; dripping water into the reactant material liquid for crystallization and then performing suction filtration, washing and drying to obtain the 4-[(3-chlorine-4-methoxyl benzyl) amino]-2-[2-(hydroxymethyl)-1-pyrrolidyl]-pyrimidine-5-nonanoic acid-ethyl ester. By adopting the micro reactor for reaction, instant full mixing of reactant materials of each reaction unit and precise control on reaction temperature can be realized, so that higher reaction yield and selectivity can be obtained, continuity and automation of a reaction process are realized, and the product is high in yield and good in quality.
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Paragraph 0036-0038
(2017/04/05)
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- A arab League cuts down that non-intermediate and its preparation method and application
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The invention discloses an avanafil intermediate as well as a preparation method and application thereof. The avanafil intermediate is a compound having a general formula as shown in the description, wherein R in the general formula is selected from C1-C4 alkyl. The preparation method of the intermediate comprises the steps a-d in the synthesis route as shown in the description. The invention also discloses an application of the intermediate. Each reaction step for preparing avanafil from the intermediate has the advantages of simple operation, mild reaction conditions, easily available reaction raw materials, high reaction yield and the like, the products are easy to separate and purify; the total yield of prepared avanafil is increased to 40% and the HPLC purity reaches up to 99.8%; the preparation cost of avanafil is greatly reduced, the quality of avanafil is ensured, and thus the intermediate is very much in line with industrial production requirements and has practical value.
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- ivah that must
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The invention provides an avanafil intermediate A and an avanafil intermediate B, and a synthetic method of the avanafil intermediates A and B and avanafil. The synthetic method of the avanafil comprises the following steps: reacting a compound with the formula (I) with 2-methylaminopyrimidine at a temperature ranging from -10 DEG C to 5 DEG C to obtain the avanafil intermediate A; agitating the avanafil intermediate A with 3-chloro-4-methoxybenzylamine at the temperature ranging from 0 DEG C to 3 DEG C and reacting for 0.2-0.4 hour to obtain the avanafil intermediate B; and agitating the avanafil intermediate B with L-prolinol at the room temperature and reacting for 18-22 hours to obtain the avanafil. The structural formulas of the avanafil intermediates A and B and the compound with the formula (I) are shown in the specification. The avanafil intermediates A and B provided by the invention are simple in structure and good in product quality; the cost of the synthetic method is low; the synthetic route of the whole process is short and reaction steps are few, so that the reaction time is shortened and the yield and the purity of the avanafil intermediates A and B, and the avanafil are also improved.
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- AVANAFIL PREPARATION METHOD
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Disclosed is a method for preparing avanafil (I) by using cytosine as the starting material. The preparation steps comprise: using cytosine as the raw material, and enabling the cytosine to react with side chain 3-chlorine-4-methoxybenzyl halogen, N-(2-methylpyrimidine) methanamide and S-hydroxymethyl pyrrolidine, to prepare the target product avanafil (I). For the preparation method, the raw material is easily obtained, and the process is simple, economical, and environmentally friendly, so the method meets the requirement of industrial boost.
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Paragraph 0035
(2016/04/09)
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- A PROCESS FOR THE PREPARATION OF AVANAFIL AND ITS NOVEL INTERMEDIATES
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The present invention relates to a novel compound of Formula (II), and its use in preparation of Avanafil, [Formula should be inserted here] wherein R is -OH, -CI or -OR1 and R1 is C1 to C3 alkyl group.
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Page/Page column 20; 21
(2015/12/11)
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- PROCESS FOR THE PREPARATION OF (S)-4-[(3-CHLORO-4-METHOXYBENZYL)AMINO]-2-[2- (HYDROXYMETHYL)-1-PYRROLIDINYL]-N-(2-PYRIMIDINYL METHYL-5-PYRIMIDINE CARBOXAMIDE
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The present invention relates to an improved process for the preparation of (S)-4-[(3- chloro-4-methoxybenzyl)amino]-2-[2-(hydroxymethyl)-1-pyrrolidinyl]-N-(2-pyrimidinyl ethyl)- 5-pyrimidine carboxamide compound of formula-1 represented by the following structural formula.
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- The discovery of avanafil for the treatment of erectile dysfunction: A novel pyrimidine-5-carboxamide derivative as a potent and highly selective phosphodiesterase 5 inhibitor
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Novel pyrimidine-5-carboxamide derivatives bearing a 3-chloro-4-methoxybenzylamino group at the 4-position were identified as potent and highly selective phosphodiesterase 5 inhibitors. Among them, we successfully found 10j (avanafil) which exhibited a potent relaxant effect on isolated rabbit cavernosum (EC30 = 2.1 nM) and a high isozyme selectivity.
- Sakamoto, Toshiaki,Koga, Yuichi,Hikota, Masataka,Matsuki, Kenji,Murakami, Michino,Kikkawa, Kohei,Fujishige, Kotomi,Kotera, Jun,Omori, Kenji,Morimoto, Hiroshi,Yamada, Koichiro
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p. 5460 - 5465
(2015/01/08)
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- POLYMORPHS OF AVANAFIL
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The present invention provides a novel polymorph of avanafil, process for its preparation and pharmaceutical compositions comprising it.
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Page/Page column 3; 6
(2014/11/13)
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- Preparations for oral administration
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The present invention provides a preparation for oral administration containing a medicinal substance having cGMP-specific phosphodiesterase inhibitory activity and showing decrease of solubility in the neutral and alkaline regions, wherein an acidic substance is compounded promote the dissolution of the medicinal substance in digestive tract and thus the efficacy can be expressed at the early stage after administration, and which preparation is useful in treatment of erectile dysfunction.
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- Aromatic nitrogen-containing 6-membered cyclic compounds
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An aromatic nitrogen-containing 6-membered cyclic compound of the formula (I): wherein Ring A is a substituted or unsubstituted nitrogen-containing heterocyclic group; R1 is a substituted or unsubstituted lower alkyl group, —NH—Q—R3 (R3 is a substituted or unsubstituted nitrogen containing heterocyclic group, and Q is a lower alkylene group or a single bond), or —NH—R4 (R4 is a substituted or unsubstituted cycloalkyl group); R2 is a substituted or unsubstituted aryl group; one of Y and Z is ═CH—, and the other is ═N—, or a pharmaceutically acceptable salt thereof, these compounds exhibiting excellent selective PDE V inhibitory activities, and hence, being useful in the prophylaxis or treatment of penile erectile dysfunction, etc.
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- TABLETS QUICKLY DISINTEGRATED IN ORAL CAVITY
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Intraorally rapidly disintegrating tablets which, when ingested, disintegrates in the oral cavity rapidly without presenting unpleasant taste, can be quickly absorbed in the digestive tract and express efficacy are provided. The intraorally rapidly disintegrating tablets contain a drug being hardly water-soluble under neutral or alkaline conditions and being highly water-soluble under acidic conditions yet presenting unpleasant taste, which tablets can be prepared by combining the medicinal substance with a water-soluble acidic substance, coating either or both of the substances with a water-soluble coating agent being insoluble in alcoholic solvent, further adding a water-soluble binding agent being soluble in alcoholic solvent and a water-soluble saccharide, subjecting the resultant mixture to compression, and treating the products with an alcoholic solvent.
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