- PROCESS FOR THE MANUFACTURING OF PIMAVANSERIN
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The present invention relates to a new process for manufacturing 1-(4-fluorobenzyl)-3-(4-iso-butoxyphenyl)-1-(1-methylpiperidin-4-yl)urea, with the INN name pimavanserin, and its hemitartrate salt.
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Page/Page column 17-18
(2020/05/28)
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- COMPOUNDS, SALTS THEREOF AND METHODS FOR TREATMENT OF DISEASES
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The present disclosure relates to compounds according to Formulae disclosed herein, useful for treating diseases.
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Paragraph 00247; 00248
(2019/03/12)
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- A method for preparing [...] (by machine translation)
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The invention discloses a method for preparing [...], comprises the following steps: 3 - chloromethyl - 4 - [...] with sodium bicarbonate reaction of material A; then with sodium hydrosulfide, sodium hydroxide reaction and get the substance B; then with 2 - chloro acetyl ethyl acetate reaction and get the substance C; then reacted with hydroxylamine hydrochloride and get the substance D, finally in the hydrolysis to obtain [...] under alkaline conditions. The material of the invention is cheap, simple and convenient operation, novel routes, environmental protection, high yield, the prepared [...] purity is good. (by machine translation)
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Paragraph 0069-0071; 0078-0080; 0087-0089; 0096-0106
(2019/04/17)
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- A vinyl [...] lin key intermediate for the preparation of (by machine translation)
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The invention discloses a matching [...] lin key intermediate of the preparation method. Synthetic route a The method of the invention the raw materials used in safety, and low cost, effectively reduces the production cost. The method of the invention mild reaction conditions, can avoid the toxicity and the operation is not easy to use phosgene, industrial is easy to realize. (by machine translation)
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Paragraph 0106; 0107; 0108; 0109; 0110; 0111; 0112
(2018/12/03)
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- Method for safely preparing pimavanserin and tartrate thereof by utilizing triphosgene
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The invention discloses a method for safely preparing pimavanserin and tartrate thereof by utilizing triphosgene. The synthetic route is as shown in the specification. The raw materials used by the method disclosed by the invention are safe, the cost is low, and the production cost is effectively reduced. The method disclosed by the invention is mild in reaction conditions, usage of phosgene thatis high in toxicity and difficult to operate can be avoided, and industrial production is easily realized.
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Paragraph 0117-0123
(2019/01/08)
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- PROCESSES AND INTERMEDIATES FOR THE PREPARATION OF PIMAVANSERIN
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The present disclosure relates to novel, safe and efficient processes for the synthesis of Pimavanserin and salts thereof, as well as novel intermediates that can be used in these processes.
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Paragraph 0134
(2018/04/17)
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- Preparation method of febuxostat intermediate, and application thereof in preparation of febuxostat
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The invention provides a preparation method of a compound of structural formula II. The method comprises the following steps: 1) reacting a compound of structural formula VII under the action of an alkylating agent and an alkali to obtain a compound of structural formula VI; 2) reacting the compound of structural formula VI to obtain a compound of structural formula V; 3) reacting the compound ofthe structural formula V with urotropine under an acidic condition in the absence of a solvent to obtain a compound of structural formula IV; 4) reacting the compound of the structural formula IV withhydroxylamine hydrochloride in the presence of an alkali, and dehydrating the obtained reaction product to obtain a compound of structural formula III; and 5) performing a ring closing reaction on the compound of the structural formula III and the compound of the structural formula VIII to obtain the compound of structural formula II. The invention also provides an application of the preparationmethod in the synthesis of febuxostat. The method has the advantages of simplicity in operation, high yield, few side reactions and no highly toxic substances, and is suitable for industrial production as a novel method for preparing the febuxostat intermediate. R in the formulas is a C1-C4 alkyl group.
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Paragraph 0096; 0097; 0099; 0100; 0102; 0103
(2018/09/11)
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- Method for Preparing Pimavanserin
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Provided is a method for preparing pimavanserin including reacting an intermediate compound represented by Formula (II) with N-(4-fluorobenzyl)-1-methylpiperidin-4-amine or a salt thereof, or reacting an intermediate compound represented by Formula (IV) with 4-isobutoxybenzylamine or a salt thereof, wherein L represents a heteroaryl group, —OR1 or halogen, and wherein R1 represents C1 to C10 alkyl or aryl. The present disclosure provides the method for preparing pimavanserin without the use of isocyanate intermediate.
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Paragraph 0031
(2018/08/11)
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- METHODS FOR PREPARING N-(4-FLUOROBENZYL)-N-(1-METHYLPIPERIDIN-4-YL)-N'-(4-(2-METHYLPROPYLOXY)PHENYLMETHYL)CARBAMIDE AND ITS TARTRATE SALT AND POLYMORPHIC FORM C
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Disclosed herein are methods for obtaining N-(4-fluorobenzyl)-N-(l-methylpiperidin-4-yl)-N'-(4-(2-methylpropyloxy)phenylmethyl) carbamide (pimavanserin) comprising the step of contacting an intermediate according to Formula (A) or a salt thereof, with an intermediate Formula B, or a salt thereof, to produce pimavanserin or a salt thereof wherein Y is -ORi or -NR2aR2b; R3 is hydrogen or substituted or unsubstituted heteroalicyclyl, R4 is substituted or unsubstituted aralkyl; X is -OR22 or -NR23R24; (wherein R22 is hydrogen or substituted or unsubstituted C1-6alkyl and one of R23 and R24 is hydrogen and the other is hydrogen or N- methylpiperidin-4-yl); and R21 is -OCH2CH(CH3)2 or F; Also disclosed herein is the tartrate salt of N-(4-fluorobenzyl)-N-(l-methylpiperidin-4-yl)-N'-(4-(2-methylpropyloxy)phenylmethyl) carbamide and methods for obtaining the salt.
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Paragraph 0213
(2017/02/09)
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- Compound 2 - (3-aldehyde group-4-isobuoxy phenyl) - 4-methyl-thiazole-5-carboxylic acid ethyl ester and non-cloth rope Tanzania method for the preparation of
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The invention provides a preparation method of 2-(3-formyl-4-isobutoxy phenyl)-4-methyl thiazole-5-ethyl formate which is obtained by using 4-isobutoxy cyanophenyl as an initial raw material and through a series of reactions. The invention also provides a preparation method of febuxostat, which comprises the following steps: reacting 2-(3-formyl-4-isobutoxy phenyl)-4-methyl thiazole-5-ethyl formate with hydroxylamine hydrochloride under the action of a catalyst to obtain a compound with a structure as shown in formula (VIII); hydrolyzing the compound with the structure as shown in formula (VIII) under an alkaline condition, and performing acidification to obtain febuxostat. The preparation method of the invention prepares febuxostat without using cyanides, and is high in safety. The preparation methods of the invention are simple in operation and high in yield. Experiment results show that the yield of step (A) is up to 90%, the yield of step (B) is up to 85%, the yield of step (C) is up to 90%, the yield of step (D) is up to 90%, and the yield of step (E) is up to 97%.
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Paragraph 0071; 0074; 0081; 0088; 0095
(2016/10/09)
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- Novel synthesis method for pimavanserin
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The invention provides a novel synthesis method for pimavanserin. The method comprises the steps that a compound formula (1a) is adopted as a raw material for preparing an active urea compound formula (1) and then subjected to a reaction with a compound formula (2) under an alkaline system to obtain a pimavanserin free alkali formula (3), and then pimavanserin free alkali forms a salt with tartaric acid to obtain a pimavanserin half tartrate formula (4). The method is simple in technological path, low in cost and suitable for industrial production. The formula is shown in the description, wherein HmA is the general formula of m-basic acid, HnA is the general formula of n-basic acid, m and n are 1 or 2 or 3, and the m-basic acid and the n-basic acid are selected from sulfuric acid, hydrochloric acid, phosphoric acid, p-toluenesulfonic acid, benzenesulfonic acid, methanesulfonic acid, methanoic acid, acetic acid, trifluoroacetic acid, oxalic acid, citric acid or tartaric acid.
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Paragraph 0065-0067
(2017/03/23)
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- 11C-labeling and preliminary evaluation of pimavanserin as a 5-HT2A receptor PET-radioligand
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Pimavanserin is a selective serotonin 2A receptor (5-HT2AR) inverse agonist that has shown promise for treatment of psychotic symptoms in patients with Parkinson's disease. Here, we detail the 11C-labeling and subsequently evaluate pimavanserin as a PET-radioligand in pigs. [11C]Pimavanserin was obtained by N-methylation of an appropriate precursor using [11C]MeOTf in acetone at 60 °C giving radiochemical yields in the range of 1-1.7 GBq (n = 4). In Danish Landrace pigs the radio ligand readily entered the brain and displayed binding in the cortex in accordance with the distribution of 5-HT2ARs. However, this binding could not be blocked by either ketanserin or pimavanserin itself, indicating high nonspecific binding. The lack of displacement by the 5-HT2R antagonist and binding in the thalamus suggests that [11C]pimavanserin is not selective for the 5-HT2AR in pigs.
- Andersen, Valdemar L.,Hansen, Hanne D.,Herth, Matthias M.,Dyssegaard, Agnete,Knudsen, Gitte M.,Kristensen, Jesper L.
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p. 1053 - 1056
(2015/02/19)
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