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Crystal and process for producing the sameRelated Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Designated Organic Active Ingredient Containing (doai), Heterocyclic Carbon Compounds Containing A Hetero Ring Having Chalcogen (i.e., O,s,se Or Te) Or Nitrogen As The Only Ring Hetero Atoms Doai, Five-membered Hetero Ring Containing At Least One Nitrogen Ring Atom (e.g., 1,2,3-triazoles, Etc.), Tetrazoles (including Hydrogenated)Crystal and process for producing the same description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20060205801, Crystal and process for producing the same. Brief Patent Description - Full Patent Description - Patent Application Claims
REFERENCE TO RELATED APPLICATIONS [0001] This application is a divisional application of U.S. patent application Ser. No. 10/485,593, now U.S. Pat. No. ______, which was the National Phase filing of International Patent Application No. PCT/JP02/07861, filed Aug. 1, 2002. TECHNICAL FIELD [0002] The present invention relates to a process for producing a crystal of 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimdazol- e-7-carboxylic acid (hereinafter, abbreviated as Compound (I) in some cases) which contains 5000 ppm or less of tetrahydrofuran, do not substantially contain contaminants such as a tin compound, analogues (e.g. ketone compound, ethyl ester compound) of 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimidazole-- 7-carboxylic acid and a residual organic solvent (e.g. dichloromethane), and is pyrogen-free and sterile, a crystal obtained by the process and a pharmaceutical composition containing the crystal. BACKGROUND ART [0003] A process for producing Compound (I) having the depressor activity or a salt thereof is described, for example, in EP-A-0881212 and EP-A-0459136. However, since Compound (I) is synthesized using an organotin compound, the organotin compound which is difficult to remove remains in the compound. In the process described in EP-A-0881212 and EP-A-0459136, about 2000 ppm (measured by atomic absorption) of a tin compound is contained in Compound (I). [0004] In addition, since the analogues such as 2,3-dihydro-2-oxo-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzi- midazole-7-carboxylic acid [hereinafter, referred to as ketone compound in some cases] and ethyl 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimdazole-7- -carboxylate [hereinafter, referred to as ethyl ester compound in some cases] have the similar properties to those of Compound (I), it is difficult to remove those analogues, and considerable amounts of them (total: about 3%) are contained in Compound (I). In addition, Compound (I) has the very low solubities in various solvents, this is one of factors making purification of Compound (I) difficult and, for this reason, a mixed solvent of dichloromethane-methanol in which Compound (I) is relatively highly soluble has been previously used in purification. As a result, highly toxic dichloromethane remains in Compound (I) at a few hundreds ppm. [0005] Like this, considerable amounts of a tin compound, analogues and dichloromethane are present in Compound (I) which has been prepared by the conventional process. However, previously, since a preparation product containing Compound (I) as an original drug is not used as a medicament, Compound (I) is derived to (.+-.)-1-(cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimidazole-- 7-carboxylate [hereinafter, referred to as candesartan cilexetil in some cases] via a number of steps, and a preparation product containing the same compound as an original drug is used as a medicament, the contaminants such as a tin compound, a ketone compound, an ethyl ester compound and dichloromethane are removed via a number of steps, and the presence of these contaminants in Compound (I) was not problematic at all. However, when a preparation product containing Compound (I) as an original drug is developed as a medicament (e.g. injectable), the presence of a tin compound, analogues and dichloromethane at an amount exceeding a tolerable amount becomes a serious problem. [0006] In the conventional process, in order to remove contaminants such as a tin compound, analogues and the like, purification was carried out using a mixed solvent of dichloromethane-methanol. However, for developing a preparation product as a medicament containing Compound (I) as an original drug, the purification efficacy of the conventional process is not sufficient, and a few thousands ppm of a tin compound and a few % of analogues remain even after purification. In addition, since dichloromethane is used as a purification solvent, a few hundreds ppm of dichloromethane remains in Compound (I). Because of the presence of such the tin compound, analogues and dichloromethane at amounts exceeding tolerable amounts, it has previously been difficult to develop a preparation product as a medicament containing compound (I) as an original drug. For this reason, there is desired a process which can afford Compound (I) containing small residual amounts of a tin compound, analogues and dichloromethane which can be employed as a medicament. DISCLOSURE OF THE INVENTION [0007] The present inventors extensively studied a process for producing a crystal of Compound (I), and first found that, when Compound (I) or a salt thereof is dissolved or suspended in a solvent containing an aprotic polar solvent to crystallize, unexpectedly, contaminants such as a tin compound, analogues (e.g. ketone compound, ethyl ester compound) of Compound (I) and a residual organic solvent (e.g. dichloromethane) which are usually difficult to remove, can be easily removed, and this process is a process which is sufficiently satisfactory on an industrial scale and, based on these findings, the present invention was completed. [0008] That is, the present invention relates to: [0009] (1) a process for producing a crystal of 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimidazole-- 7-carboxylic acid, which comprises dissolving or suspending 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimidazole-- 7-carboxylic acid or a salt thereof in a solvent containing an aprotic polar solvent, and crystallizing it, [0010] (2) a process for producing a crystal of 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimidazole-- 7-carboxylic acid, which comprises crystallizing from a solution or suspension containing 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimidazole-- 7-carboxylic acid or a salt thereof and an aprotic polar solvent, [0011] (2') a process for producing a crystal of 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimidazole-- 7-carboxylic acid, which comprises crystallizing from a solution containing 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimidazole-- 7-carboxylic acid and an aprotic polar solvent, [0012] (3) a process for producing a crystal of 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimidazole-- 7-carboxylic acid, which comprises dissolving or suspending 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimidazole-- 7-carboxylic acid or a slat thereof in a solvent containing an aprotic polar solvent, followed by mixing the solution or suspension with water and/or an organic solvent to crystallize, [0013] (4) the process according to the above-mentioned (3), wherein the solvent containing an aprotic polar solvent is a mixed solvent containing an aprotic polar solvent and water, [0014] (5) the process according to the above-mentioned (3), wherein the solvent containing an aprotic polar solvent is a mixed solvent containing an aprotic polar solvent and an organic solvent, [0015] (6) the process according to the above-mentioned (3), wherein the solvent containing an aprotic polar solvent is a mixed solvent containing an aprotic polar solvent, water and an organic solvent, [0016] (7) the process according to the above-mentioned (3), wherein 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimidazole-- 7-carboxylic acid or a salt thereof is dissolved or suspended in a solvent containing an aprotic polar solvent, followed by mixing the solution or suspension with an organic solvent to crystallize, [0017] (8) the process according to the above-mentioned (3), wherein 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimidazole-- 7-carboxylic acid or a salt thereof is dissolved or suspended in a solvent containing an aprotic polar solvent, followed by mixing the solution or suspension with water and an organic solvent to crystallize, [0018] (9) the process according to the above-mentioned (1), (2), (2') or (3), wherein the aprotic polar solvent is one or more kinds of solvents selected from tetrahydrofuran, dimethylformamide, dimethyl sulfoxide and hexamethylphosphoric triamide, [0019] (10) the process according to the above-mentioned (1), (2), (2') or (3), wherein the aprotic polar solvent is tetrahydrofuran, [0020] (11) the process according to the above-mentioned (1), (2), (2') or (3), comprising crystallizing at about 0 to about 30.degree. C., Continue reading about Crystal and process for producing the same... Full patent description for Crystal and process for producing the same Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Crystal and process for producing the same patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. Each week you receive an email with patent applications related to your keywords. Start now! - Receive info on patent apps like Crystal and process for producing the same or other areas of interest. ### Previous Patent Application: Anti-cancer and anti-microbial oxazolidinones Next Patent Application: Therapeutic compounds Industry Class: Drug, bio-affecting and body treating compositions ### FreshPatents.com Support Thank you for viewing the Crystal and process for producing the same patent info. 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