公开(公告)号：US4421913A

公开(公告)日：1983-12-20

申请号：US329869

申请日：1981-12-11

申请人： James A. Ellard ,  James A. Webster

发明人： James A. Ellard ,  James A. Webster

IPC分类号： C07D475/08

CPC分类号： C07D475/08 ,  Y02P20/55

摘要： An improvement in the production of methotrexate as set out in Ellard U.S. Pat. No. 4,080,325. It has been found that magnesium oxide facilitates the coupling reaction by acting as an acid acceptor. The dense grade of magnesium oxide is preferred in molar proportions of 2 to 4 moles of magnesium oxide per mole of 2,4-diamino-6-hydroxymethylpteridine. Further, the triphenylphosphine oxide which is generated by hydrolysis of the protecting groups is removed from the reaction stream by utilization of toluene or BTX-type solvents.

摘要翻译： 在埃拉德美国专利中提出的甲氨蝶呤的生产改善。 4,080,325。 已经发现氧化镁通过用作酸受体来促进偶联反应。 按每摩尔2,4-二氨基-6-羟甲基脒的摩尔比为2〜4摩尔的氧化镁，氧化镁的致密等级优选。 此外，通过利用甲苯或BTX型溶剂从反应流中除去由保护基水解产生的三苯基氧化膦。

公开(公告)号：US3955987A

公开(公告)日：1976-05-11

申请号：US462273

申请日：1974-04-19

申请人： John L. Schaar ,  James A. Ellard ,  John Mann Butler

发明人： John L. Schaar ,  James A. Ellard ,  John Mann Butler

IPC分类号： C09D5/18 ,  C09K21/04 ,  C09K3/28

CPC分类号： C09K21/04 ,  C09D5/185 ,  Y10S260/24 ,  Y10S428/92 ,  Y10S428/921

摘要： Intumescent compositions are described which when deposited on a substrate protect the substrate against heat and fire damage for an appreciable time, and these compositions are readily removed from the substrate by water washing or water scrubbing both before and after intumescing. Another advantage of these compositions is that they give off very little smoke when exposed to heat and fire. The most effective of these compositions comprise monoammonium phosphate and/or diammonium phosphate as a heat- and fireproofing agent, urea and/or cyanoguanidine (dicyandiamide) as a gas forming or gas generating agent to promote the intumescence, sucrose (sugar) together with the phosphate to promote initial intumescence at low temperature and titanium dioxide as a heat-reflecting agent. Certain possible alternatives to the compounds named above are also named.

摘要翻译： 描述了膨胀组合物，当沉积在基材上时，保护基材免受热和火焰损伤一段可观的时间，并且这些组合物通过在浸泡之前和之后的水洗或水洗均可容易地从基材上除去。 这些组合物的另一个优点是当暴露于热和火时它们发出很少的烟雾。 这些组合物中最有效的包括作为耐火和防火剂的磷酸氢二铵和/或磷酸氢二铵，作为促进膨胀的气体形成或气体发生剂的尿素和/或氰基胍（双氰胺），蔗糖（糖） 磷酸盐以促进低温下的初始膨胀和作为热反射剂的二氧化钛。 上述化合物的某些可能的替代物也被命名。

公开(公告)号：US4080325A

公开(公告)日：1978-03-21

申请号：US742450

申请日：1976-11-17

申请人： James A. Ellard

发明人： James A. Ellard

IPC分类号： C07D475/08 ,  C07F9/535

CPC分类号： C07D475/08 ,  C07F9/5355 ,  Y02P20/55

摘要： The present invention consists of three process improvements in the so-called multi-step Piper-Montgomery process designed especially to produce the antifolate methotrexate which is closely related to both aminopterin and folic acid. 2,4,5,6-tetraaminopyrimidine sulfite is one starting material and is usually produced in the form of the bisulfite in an acetate buffer. The present modification positively produces the hydrochloride from the bisulfite and eliminates the acetate buffer utilized in prior art processes. Subsequently, a pteridine ring is formed from the pyrimidine hydrochloride using dihydroxyacetone at pH 5.5.+-.0.2 to form the second ring. This strict pH control together with the use of hydrochloride salt minus the acetate buffer assists in preferentially favoring the formation of 2,4-diamino-6-hydroxymethylpteridine. Subsequently the 6-hydroxy-methyl compound is converted to the hydrobromide acid salt and reacted with three moles of a triphenyl dibromophosphorane and phosphazine protecting groups are formed on the amine groups of the pteridine ring as the 6-hydroxymethyl group is transformed to 6-bromomethyl, a key intermediate. The present process leaves the protecting phosphazine groups on the primary amino groups to discourage side reactions during subsequent alkylation of the other major reactant, ethyl N-(p-methylaminobenzoyl)-L-glutamate. Furthermore, ethyl N-(p-methylaminobenzoyl)-L-glutamate, the other reactant, is uniquely produced for the present multi-step reaction by a process proceeding from ethyl N-(p-trifluoromethylaminobenzoyl)-L-glutamate by utilizing an alkali metal hydroxide in a lower (C.sub.1 -C.sub.6) alkanol wherein the protective trifluoroacetyl groups are removed. This step uses a special mixture preferably of an alkali metal hydroxide in ethanol and optimally 1 equivalent of KOH in 20% ethanol at or below ambient temperature where the mixture is added slowly to keep the reaction pH below 9. The combination of these improvements results in the increase of an overall yield of methotrexate from the named starting reactants from about 25% to approximately 40-50%.

公开(公告)号：US4306064A

公开(公告)日：1981-12-15

申请号：US133788

申请日：1980-03-25

申请人： James A. Ellard ,  Joseph Satanek, Jr.

发明人： James A. Ellard ,  Joseph Satanek, Jr.

IPC分类号： C07D475/06 ,  C07D475/08

CPC分类号： C07D475/06

摘要： In a method of preparing methotrexate from a coupling of 2,4-bis(triphenylphosphazino)-6-bromomethylpteridine hydrobromide with ethyl N-(p-methylamino)-benzoyl-L-glutamate to produce the phosphazino derivative of methotrexate ester and subsequently hydrolyzing the phosphazino and ester groups to produce the free methotrexate, the pteridine synthesis step wherein molecular oxygen is substituted for reaction air and the pH throughout the pteridine synthesis is regulated to between 2.5 and 5.4, the preferred pH being about 3.0 and producing from tetraaminopyrimidine and dihydroxyacetone the isomer 2,4-diamino-6-hydroxymethylpteridine over 2,4-diamino-7-hydroxymethylpteridine in a ratio of about 20:1. Exemplary of other situations involving pteridine where the molecular oxygen may be substituted for reaction air are: in the production of folic acid, tetrahydrofolic acid, etc.

摘要翻译： 在从2,4-双（三苯基膦基）-6-溴甲基蝶啶氢溴酸盐与N-（对甲基氨基） - 苯甲酰基-L-谷氨酸乙酯偶合制备甲氨蝶呤的方法中，产生甲氨蝶呤磷酸酯衍生物，随后水解 磷酰基和酯基以产生游离甲氨蝶呤，蝶啶合成步骤，其中分子氧被代替反应空气，整个蝶啶合成中的pH被调节到2.5至5.4之间，优选的pH为约3.0，由四氨基嘧啶和二羟基丙酮 异构体2,4-二氨基-6-羟甲基ter啶以比例约为20:1的2,4-二氨基-7-羟甲基ter啶。 其中分子氧可以代替反应空气的其他涉及蝶啶的情况是：在叶酸，四氢叶酸等的生产中

公开(公告)号：US4246358A

公开(公告)日：1981-01-20

申请号：US103977

申请日：1979-12-17

申请人： James A. Ellard

发明人： James A. Ellard

IPC分类号： C08J9/02 ,  C08L27/08 ,  C08L61/20 ,  C08L81/10

CPC分类号： C08L27/08 ,  C08J9/02 ,  C08L61/20 ,  C08L81/10

摘要： Fire-resistant organic materials including foams, are made by heating at temperatures sufficient to cause polymerization and elimination of nitrogen and sulfur precursor aromatic polymers having sulfonamide linkages and aromatic compounds capable of forming said polymers, e.g. sulfamyl-type aminoaromatic compounds such as sulfanilamide, sulfaguanadine and the like. Preferred compounds are those providing para linkages in the sulfonamide polymer chain, those which are substantially free of oxidizing substituents, for example nitro groups, and those which are not fused-ring aromatic. Preferred foams are the high expansion foams, i.e. those having expansion ratios of at least about 3:1, more preferably at least about 8:1. The precursors of these fire-resistant organic materials can be incorporated into polymers such as polyvinylidene chloride, polyisocyanates, aminoplasts, and the like either physically by mixing or by chemical reaction to give improved fire-resistance. Also inorganic fillers such as titanium dioxide, silica, alumina and the like can be added to the polymers and/or the precursor to give compositions having improved fire resistance.

摘要翻译： 包括泡沫在内的耐火有机材料通过在足以引起聚合和消除具有磺酰胺键的氮和硫前体芳族聚合物和能够形成所述聚合物的芳族化合物的温度下加热制备，例如， 磺酰胺型氨基芳族化合物如磺胺，磺胺胍等。 优选的化合物是在磺酰胺聚合物链中提供对键，那些基本上不含氧化取代基的化合物，例如硝基，以及不是稠环芳族的化合物。 优选的泡沫是高膨胀泡沫，即具有至少约3:1，更优选至少约8:1的膨胀比的那些。 这些耐火有机材料的前体可以通过混合或通过化学反应物理地掺入到聚偏二氯乙烯，多异氰酸酯，氨基塑料等聚合物中，以提高耐火性。 还可以向聚合物和/或前体中加入无机填料，例如二氧化钛，二氧化硅，氧化铝等，得到具有改善耐火性的组合物。