公开(公告)号：US5654486A

公开(公告)日：1997-08-05

申请号：US620824

申请日：1996-03-25

申请人： K. Pushpananda A. Senaratne ,  Arcelio J. Malcolm ,  Felix M. Orihuela ,  Hassan Y. Elnagar

发明人： K. Pushpananda A. Senaratne ,  Arcelio J. Malcolm ,  Felix M. Orihuela ,  Hassan Y. Elnagar

IPC分类号： C07F9/50

CPC分类号： C07F9/5077

摘要： Partially sterically-hindered cycloalkyl chlorides are reacted with lithium diarylphosphides in inert liquid hydrocarbon reaction media to form cycloalkyldiarylphosphines. Aryl lithium is coproduced. The process makes it possible to avoid, or at least substantially eliminate, the interaction with or cleavage of cyclic ether reaction media such as tetrahydrofuran, previously the solvent of choice for conducting this type of reaction. Also during the conduct of the present process the chloro-substituted cycloalkane does not undergo any appreciable reaction with the coproduced aryl lithium as it is formed. Thus improvements both in yield and quality of the cycloalkyldiarylphosphine product are made possible. A comprehensive three-step process for converting triarylphosphine to cycloalkyldiarylphosphine is also described.

摘要翻译： 部分空间位阻环烷基氯与惰性液体烃反应介质中的二芳基磷化锂反应形成环状二芳基膦。 共生产芳基锂。 该方法使得可以避免或至少基本上消除环醚反应介质如四氢呋喃的相互作用或切割，其中先前是用于进行这种反应的溶剂。 此外，在本方法的进行过程中，氯取代的环烷烃在形成时不与共同生产的芳基锂发生任何明显的反应。 因此，可以改善环烷基二芳基膦产物的产率和质量。 还描述了将三芳基膦转化为环烷基二芳基膦的综合三步法。

公开(公告)号：US08940329B2

公开(公告)日：2015-01-27

申请号：US11260662

申请日：2005-10-28

申请人： Patrick C. Hu ,  Gregory H. Lambeth ,  Arcelio J. Malcolm

发明人： Patrick C. Hu ,  Gregory H. Lambeth ,  Arcelio J. Malcolm

IPC分类号： A61K9/20 ,  A01N37/10 ,  A61K31/19 ,  A61K9/16 ,  A61K31/192

CPC分类号： A61K9/2077 ,  A61K9/1652 ,  A61K9/1688 ,  A61K9/1694 ,  A61K9/2059 ,  A61K31/192

摘要： Described are granules composed at least of a substantial amount of ibuprofen, at least one pharmaceutically-acceptable super disintegrant, and at least one pharmaceutically-acceptable binder different from the super disintegrant(s), the super disintegrant(s) being substantially uniformly dispersed throughout the granules. The methods for preparing such granules are described. The granules are useful in forming solid dosage forms such as filled capsules or compressed solid dosage forms.

摘要翻译： 描述了至少包含大量布洛芬，至少一种药学上可接受的超级崩解剂和至少一种不同于超级崩解剂的药学上可接受的粘合剂的颗粒，所述超级崩解剂基本均匀地分散在整个 颗粒。 描述了制备这种颗粒的方法。 颗粒可用于形成固体剂型，例如填充胶囊或压缩固体剂型。

公开(公告)号：US5856501A

公开(公告)日：1999-01-05

申请号：US989096

申请日：1997-12-11

申请人： Arcelio J. Malcolm ,  Tse-Chong Wu

发明人： Arcelio J. Malcolm ,  Tse-Chong Wu

IPC分类号： C07D277/38 ,  C07D277/46 ,  C07D277/48

CPC分类号： C07D277/48

摘要： N-�4-(cyanoethylthiomethyl)-2-thiazolyl!guanidine--a key intermediate for preparing the pharmaceutical, famotidine--is produced by mixing in a liquid medium formed from a chemically indifferent organic solvent and water, and under an inert atmosphere, (i) a 2-guanidino-4-halomethylthiazole or a hydrohalide complex thereof, (ii) an S-(2-cyanoethyl)isothiourea or a hydrohalide complex thereof, and (iii) a strong alkali metal base. In lieu of (ii), an alkali metal salt of 2-cyanoethyl-1-thiol can be used, and in such case use of (iii) is optional, but preferable.

摘要翻译： N- [4-（氰基乙硫基甲基）-2-噻唑基]胍 - 用于制备药物法莫替丁的关键中间体 - 通过在由化学无关的有机溶剂和水形成的液体介质中混合，并在惰性气氛下， i）2-胍基-4-卤代甲基噻唑或其氢卤化物络合物，（ii）S-（2-氰基乙基）异硫脲或其氢卤化物络合物，和（iii）强碱金属碱。 代替（ii），可以使用2-氰基乙基-1-硫醇的碱金属盐，在这种情况下，使用（iii）是任选的，但优选。

公开(公告)号：US5710299A

公开(公告)日：1998-01-20

申请号：US672128

申请日：1996-06-27

申请人： Meng-Sheng Ao ,  Hassan Y. Elnagar ,  Arcelio J. Malcolm ,  Jamie R. Strickler

发明人： Meng-Sheng Ao ,  Hassan Y. Elnagar ,  Arcelio J. Malcolm ,  Jamie R. Strickler

IPC分类号： C07C1/24 ,  C07C13/547 ,  C07C29/143 ,  C07C35/37 ,  C07C45/00 ,  C07C49/675 ,  C07F7/00 ,  C07F7/08 ,  C07F7/22 ,  C07F7/30 ,  C07F17/00

CPC分类号： C07F7/0827 ,  C07F17/00 ,  C07F7/2212 ,  C07F7/30 ,  Y10S526/943

摘要： Bridged metallocene compounds are produced by a process of promising commercial utility for plant-sized operations. The overall process involves the direct conversion of benzoindanones to benzoindanols which, without isolation, are converted to benzoindenes. Thereupon the benzoindenes are bridged by deprotonating the benzoindenes with a strong base such as butyllithium and reacting the resultant deprotonated product with a suitable silicon-, germanium- or tin-containing bridging reactant such as dichlorodimethylsilane. The resultant bridged product is deprotonated with a strong base such as butyllithium and reacted with a suitable Group IV, V, or VI metal-containing reactant such as ZrCl.sub.4 to provide a silicon-, germanium- or tin-bridged Group IV, V, or VI metal complex, such as a dihydrocarbylsilyl-bridged zirconocene complex. The initial benzoindenones used in such sequence can be formed readily and in high yield by reaction of a 2-haloacyl halide with naphthalenes unsubstituted in at least the 1- and 2-positions.

摘要翻译： 桥接的茂金属化合物是通过有希望的用于植物大小的操作的商业应用的方法生产的。 整个方法包括将苯并二氢醌直接转化为苯并二醇，其不经分离转化成苯并茚基。 因此，苯并茚基通过用强碱如丁基锂对苯并茚进行去质子化来桥接，并使得到的去质子化产物与合适的含硅，锗或锡的桥连反应物如二氯二甲基硅烷反应。 所得的桥连产物用强碱如丁基锂去质子化并与合适的含IV，V或VI族金属的反应物如ZrCl 4反应以提供硅，锗或锡桥连的IV族V，或 VI金属络合物，例如二烃基甲硅烷基桥接的茂锆复合物。 在这种顺序中使用的初始苯并茚酮可以通过2-卤代酰卤与至少1位和2位未取代的萘反应而容易地且高产率地形成。

公开(公告)号：US5856500A

公开(公告)日：1999-01-05

申请号：US816112

申请日：1997-03-11

申请人： Michael D. Matthews ,  Arcelio J. Malcolm

发明人： Michael D. Matthews ,  Arcelio J. Malcolm

IPC分类号： C07D277/48 ,  C07D277/18

CPC分类号： C07D277/48

摘要： N-�4-(Cyanoethylthiomethyl)-2-thiazolyl!guanidine, is prepared by (a) mixing 1,3-dihaloacetone and 2-imino-4-thiobiuret in a suitable polar organic solvent at initial temperatures of about -10.degree. to about 25.degree. C., and agitating the mixture at about -10.degree. to about 60.degree. C. for at least about 1 hour; (b) heating the resultant mixture at about 40.degree. to about 60.degree. C. for at least about 0.5 hour; (c) mixing with the mixture from (b), thiourea and then water at about 40.degree. to about 60.degree. C. for a period of at least about 1 hour; (d) removing liquid polar solvent from the mixture of (c); and (e) mixing with the mixture from (d), 3-halopropionitrile and water-soluble alcohol, ether, or ether-alcohol, followed by aqueous alkali metal hydroxide while maintaining the temperature at below about 20.degree. C., to form N-�4-(cyanoethylthiomethyl)-2-thiazolyl!guanidine. The process avoids isolating and purifying any of the intermediates, and can be conducted in the same vessel, as a "one-pot" synthesis.

摘要翻译： 通过以下步骤制备N- [4-（氰基乙硫基甲基）-2-噻唑基]胍：（a）将1,3-二卤代丙酮和2-亚氨基-4-硫代嘌呤在合适的极性有机溶剂中混合，初始温度为约-10℃至 约25℃，并将混合物在约-10℃至约60℃搅拌至少约1小时; （b）在约40℃至约60℃下加热所得混合物至少约0.5小时; （c）在约40℃至约60℃下与（b），硫脲和然后水的混合物混合至少约1小时; （d）从（c）的混合物中除去液体极性溶剂; 和（e）与来自（d），3-卤代丙腈和水溶性醇，醚或醚 - 醇的混合物，然后与碱金属氢氧化物水溶液混合，同时保持温度低于约20℃，形成N - [4-（氰基乙硫基甲基）-2-噻唑基]胍。 该方法避免了分离和纯化任何中间体，并且可以作为“一锅”合成在同一容器中进行。

公开(公告)号：US4670574A

公开(公告)日：1987-06-02

申请号：US908736

申请日：1986-09-18

申请人： Arcelio J. Malcolm ,  Charles R. Everly ,  Gunner E. Nelson

发明人： Arcelio J. Malcolm ,  Charles R. Everly ,  Gunner E. Nelson

IPC分类号： C07F7/08

CPC分类号： C07F7/0896

摘要： Silane and monoalkylsilanes can be alkylated using an alkali metal aluminate, MAlR.sub.4, wherein M is Li, Na, or K and each R is a straight chain, alkyl radical solely composed of carbon and hydrogen containing from about 4 to about 18 carbon atoms. The aluminate can be used as a reactant, optionally in the presence of a straight chain alpha-olefin corresponding to the alkyl group in the aluminate. Alternatively, the aluminate can be used as a catalyst for the reaction of the olefin and the silane reactant, in which case from about 5 to about 10 mole percent of the aluminate (based on the silane reactant) is employed. The catalytic reaction is promoted by a smaller amount of a lithium salt such as lithium chloride. Both embodiments are conducted at somewhat elevated temperatures, approximately 160.degree.-210.degree. C., and at autogenous pressures, using reaction times of 8-20 hours.The products are useful as functional fluids or as intermediates.

摘要翻译： 硅烷和单烷基硅烷可以使用碱金属铝酸盐MA1R4烷基化，其中M是Li，Na或K，并且每个R是直链，仅由碳组成的烷基和含有约4至约18个碳原子的氢。 铝酸盐可以用作反应物，任选地在对应于铝酸盐中的烷基的直链α-烯烃的存在下使用。 或者，铝酸盐可以用作烯烃和硅烷反应物的反应的催化剂，在这种情况下，使用约5至约10摩尔％的铝酸盐（基于硅烷反应物）。 催化反应由较少量的锂盐如氯化锂促进。 两个实施方案在稍高的温度下进行，约160℃-210℃，并且在自生压力下，使用8-20小时的反应时间进行。 该产品可用作功能性液体或作为中间体。

公开(公告)号：US06020284A

公开(公告)日：2000-02-01

申请号：US149992

申请日：1998-09-09

申请人： K. Pushpananda A. Senaratne ,  Felix M. Orihuela ,  Arcelio J. Malcolm

发明人： K. Pushpananda A. Senaratne ,  Felix M. Orihuela ,  Arcelio J. Malcolm

IPC分类号： C01G9/04 ,  C07C17/16 ,  B01J27/138

CPC分类号： C07C17/16 ,  C01G9/04 ,  Y02P20/582

摘要： Gaseous anhydrous hydrogen chloride is introduced into an aqueous solution of zinc chloride under conditions effective to produce a more efficient Lucas reagent than a Lucas reagent made by mixing solid, anhydrous zinc chloride with 38% hydrochloric acid. For example, the reaction rate of such Lucas reagent with levo-menthol is much faster and requires a much shorter reaction period than Lucas reagent formed in the conventional manner from anhydrous, solid zinc chloride and concentrated (38%) hydrochloric acid. Also, the conversion to levo-menthyl chloride was higher when using Lucas reagent formed using gaseous anhydrous hydrogen chloride and aqueous zinc chloride solution. Also, Lucas reagent made in this manner is highly amenable to recycling, and requires only addition thereto of hydrogen chloride to replenish the catalyst for an ensuing run.

摘要翻译： 将气态无水氯化氢引入到氯化锌水溶液中，该条件有效地产生比通过将固体无水氯化锌与38％盐酸混合的Lucas试剂更有效的Lucas试剂。 例如，这种Lucas试剂与左旋薄荷醇的反应速度要快得多，并且比用无水固体氯化锌和浓缩（38％）盐酸以常规方式形成的Lucas试剂要短得多的反应时间。 此外，当使用使用气态无水氯化氢和氯化锌水溶液形成的Lucas试剂时，转化为氯化叶绿素较高。 此外，以这种方式制备的Lucas试剂高度易于再循环，并且仅需要加入氯化氢来补充催化剂用于随后的运行。

公开(公告)号：US5861522A

公开(公告)日：1999-01-19

申请号：US853698

申请日：1997-05-08

申请人： Meng-Sheng Ao ,  Hassan Y. Elnagar ,  Arcelio J. Malcolm ,  Jamie R. Strickler ,  Ronny W. Lin ,  John F. Balhoff

发明人： Meng-Sheng Ao ,  Hassan Y. Elnagar ,  Arcelio J. Malcolm ,  Jamie R. Strickler ,  Ronny W. Lin ,  John F. Balhoff

IPC分类号： C07C1/24 ,  C07C13/547 ,  C07C29/143 ,  C07C35/37 ,  C07C45/00 ,  C07C49/675 ,  C07F7/00 ,  C07F7/08 ,  C07F7/22 ,  C07F7/30 ,  C07F17/00

CPC分类号： C07F7/0827 ,  C07F17/00 ,  C07F7/2212 ,  C07F7/30 ,  Y10S526/943

摘要： Bridged metallocene compounds are produced by a process of promising commercial utility for plant-sized operations. One of the key steps of the process involves converting a deprotonated silicon-, germanium- or tin-containing ligand into the metallocene. Preferably, and in accordance with an embodiment of the invention, this is accomplished to great advantage by adding a diamine adduct of a Group IV, V, or VI metal tetrahalide to a solution or slurry formed from a deprotonated silicon-, germanium- or tin-containing ligand and an organic liquid medium so as to form a metallocene. The overall process of the invention involves the direct conversion of benzoindanones to benzoindanols which, without isolation, are converted to benzoindenes. Thereupon the benzoindenes are bridged by deprotonating the benzoindenes with a strong base such as butyllithium and reacting the resultant deprotonated product with a suitable silicon-, germanium- or tin-containing bridging reactant such as dichlorodimethylsilane. The resultant bridged product is deprotonated with a strong base such as butyllithium and reacted with a suitable Group IV, V, or VI metal-containing reactant such as ZrCl.sub.4 to provide a silicon-, germanium- or tin-bridged Group IV, V, or VI metal complex, such as a dihydrocarbylsilyl-bridged zirconocene complex.

摘要翻译： 桥接的茂金属化合物是通过有希望的用于植物大小的操作的商业应用的方法生产的。 该方法的关键步骤之一涉及将去质子化的含硅或锗的配体转化为茂金属。 优选地，并且根据本发明的一个实施方案，这通过将IV，V或VI族金属四卤化物的二胺加合物加入到由去质子化的硅，锗或锡形成的溶液或浆料中来实现， 的配体和有机液体介质，以形成茂金属。 本发明的总体方法涉及将苯并二氢醌直接转化为苯并二醇，其不经分离转化为苯并茚基。 因此，苯并茚基通过用强碱如丁基锂对苯并茚进行去质子化来桥接，并使得到的去质子化产物与合适的含硅，锗或锡的桥连反应物如二氯二甲基硅烷反应。 所得的桥连产物用强碱如丁基锂去质子化并与合适的含IV，V或VI族金属的反应物如ZrCl 4反应以提供硅，锗或锡桥连的IV族V，或 VI金属络合物，例如二烃基甲硅烷基桥接的茂锆复合物。

公开(公告)号：US5731442A

公开(公告)日：1998-03-24

申请号：US816111

申请日：1997-03-11

申请人： Arcelio J. Malcolm ,  Tse-Chong Wu

发明人： Arcelio J. Malcolm ,  Tse-Chong Wu

IPC分类号： C07D277/38 ,  C07D277/46 ,  C07D277/48

CPC分类号： C07D277/48

摘要： N-�4-(cyanoethylthiomethyl)-2-thiazolyl!guanidine--a key intermediate for preparing the pharmaceutical, famotidine--is produced by mixing in a liquid medium formed from a chemically indifferent organic solvent and water, and under an inert atmosphere, (i) a 2-guanidino-4-halomethylthiazole or a hydrohalide complex thereof, (ii) an S-(2-cyanoethyl)isothiourea or a hydrohalide complex thereof, and (iii) a strong alkali metal base. In lieu of (ii), an alkali metal salt of 2-cyanoethyl-1-thiol can be used, and in such case use of (iii) is optional, but preferable.

公开(公告)号：US5654485A

公开(公告)日：1997-08-05

申请号：US620823

申请日：1996-03-25

申请人： K. Pushpananda A. Senaratne ,  Arcelio J. Malcolm ,  Felix M. Orihuela ,  Hassan Y. Elnagar

发明人： K. Pushpananda A. Senaratne ,  Arcelio J. Malcolm ,  Felix M. Orihuela ,  Hassan Y. Elnagar

IPC分类号： C07F9/50

CPC分类号： C07F9/5077

摘要： By reacting certain partially sterically-hindered chloro-substituted cycloalkanes with sodium and/or potassium diarylphosphides in an ether reaction medium, not only are useful cycloalkyldiarylphosphines produced, but in addition the chloro-substituted cycloalkane does not undergo any appreciable reaction with the coproduced aryl sodium and/or aryl potassium as it is formed. Moreover, the process makes it possible to avoid or at least to greatly reduce interaction with or cleavage of cyclic ether reaction media such as tetrahydrofuran. Thus the process makes possible improvements both in yield and quality of the cycloalkyldiarylphosphite product. A two-stage process conducted in an ether reaction medium is also described. In the first stage the sodium and/or potassium diarylphosphine reactant is produced by reaction between sodium and/or potassium and triarylphosphine.

摘要翻译： 通过使某些部分空间位阻的氯取代的环烷烃与醚反应介质中的二芳基磷酸钠和/或钾反应，不仅产生了有用的环烷基二芳基膦，而且氯取代的环烷烃与共同生产的芳基钠不会发生明显的反应 和/或芳基钾。 此外，该方法可以避免或至少大大降低与环醚反应介质如四氢呋喃的相互作用或裂解。 因此，该方法可以改善环烷基二芳基亚磷酸酯产物的产率和质量。 还描述了在醚反应介质中进行的两阶段方法。 在第一阶段，二钠和/或二芳基膦反应物是通过钠和/或钾与三芳基膦之间的反应产生的。