7-chloro-benzo[g]pteridine-2,4(3H,10H)-dione | 3273-42-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 蝶啶及其衍生物
• 英文名称: 7-chloro-benzo[g]pteridine-2,4(3H,10H)-dione
• 英文别名: 7-Chloroalloxazine；7-chloro-1H-benzo[g]pteridine-2,4-dione
• CAS: 3273-42-5
• 化学式: C₁₀H₅ClN₄O₂
• 分子量: 248.628
• InChiKey: KBOXHAALUDKSPW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  84
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-硝基苯胺盐酸盐 在 镍 盐酸 、 一水合肼 、 溶剂黄146 、 copper(l) chloride 、 sodium nitrite 、 正丁醇 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.5h， 生成 7-chloro-benzo[g]pteridine-2,4(3H,10H)-dione
  参考文献：
  名称：

  Tul'chinskaya, L. S.; Polyakova, N. A.; Zapesochnaya, L. G., Journal of Organic Chemistry USSR (English Translation), 1981, vol. 17, p. 917 - 923

  摘要：

  DOI：

文献信息

• Synthesis of Riboflavines, Quinoxalinones and Benzodiazepines through Chemoselective Flow Based Hydrogenations
  作者：Marcus Baumann、Ian Baxendale、Christian Hornung、Steven Ley、Maria Rojo、Kimberley Roper

  DOI：10.3390/molecules19079736

  日期：——

  Robust chemical routes towards valuable bioactive entities such as riboflavines, quinoxalinones and benzodiazepines are described. These make use of modern flow hydrogenation protocols enabling the chemoselective reduction of nitro group containing building blocks in order to rapidly generate the desired amine intermediates in situ. In order to exploit the benefits of continuous processing the individual steps were transformed into a telescoped flow process delivering selected benzodiazepine products on scales of 50 mmol and 120 mmol respectively.

  描述了通向有价值的生物活性实体（如核黄素、喹唑啉酮和苯二氮卓）的稳健化学路线。这些路线利用现代流动加氢协议，能够对含有硝基的构筑块进行化学选择性的还原，从而迅速在原位生成所需的胺中间体。为了利用连续加工的优势，各个步骤被转化为一个串联流动过程，分别以50毫摩尔和120毫摩尔的规模生产选定的苯二氮卓产品。
• (3-amino-5, 6-disubstituted-pyrazinoyl) guanidines
  申请人：MERCK &

  公开号：US03313813A1

  公开（公告）日：1967-04-11

  The invention comprises compounds of the general formula I <;FORM:1066855/C2/1>; in which X is a hydrogen or halogen atom, a trihalomethyl, C1- 6 alkyl, C3 to C6 cycloalkyl, mononuclear aryl, anilino, C1- 5 alkylthio, C1- 5-alkylsulphonyl, phenyl-substituted C1- 5 alkylthio or phenyl-substituted C1- 5 alkylsulphonyl; Y is a hydrogen or halogen atom or a hydroxyl, mercapto, C1- 5 alkoxy, C1- 5 alkylthio, C1- 6 alkyl, C3- 6 cycloalkyl, mononuclear aryl or 4-methyl-1-piperazinyl group or an amino group of the formula -NRR1, wherein R is a hydrogen atom or an amino, amidino, C3- 6 cycloalkyl, C1- 6 alkyl, hydroxy-substituted C1- 6 alkyl, halogen-substituted C1- 6 alkyl, (C3- 6 cycloalkyl)-(C1- 5 alkyl), phenyl-substituted C1- 5 alkyl, (C1- 5 alkyl) phen-(C1- 5 alkyl), halophenyl-substituted C1- 5 alkyl, furyl-substituted C1- 5 alkyl, pyridyl-substituted C1- 5 alkyl, C1- 5 alkylamino (C1- 5 alkyl), C2- 6 alkenyl, b -aminoethyl, phenyl, halophenyl or (C1- 5 alkyl) phenyl radical and R1 is a hydrogen atom or a C1- 6 alkyl or C2- 6 alkenyl radical or R and R1 are joined to form a C2- 6 alkylene radical, but with the proviso that Y is not hydrogen when X is hydrogen, halogen or trihalomethyl; or X and Y together form a tetramethylene, 1,3-butadienylene or 2-chloro-1,3-butadienylene radical; Z is an amino, monosubstituted amino, disubstituted amino, or heterocyclic amino radical; R2 is a hydrogen atom or a C1- 6 alkyl radical; each of R3 and R4 is a hydrogen atom or a C1- 6 alkyl, hydroxy-substituted C1- 6 alkyl, phenyl-substituted C1- 5 alkyl, halophenyl-substituted C1- 5 alkyl, (C1- 5 alkyl) phen-(C1- 5 alkyl), (C1- 5 alkoxyphenyl) substituted C1- 5 alkyl, naphthyl-substituted C1- 5 alkyl, (octahydro-1-azocinyl)-substituted C1- 5 alkyl, pyridyl-substituted C1- 5 alkyl, or phenyl radical; or R3 and R4, together with the nitrogen atom to which they are attached, represent a 1-pyrrolidinyl, piperidino, morpholino, or 4-(C1- 4 alkyl)-piperazinyl group and pharmaceutically acceptable salts thereof. These compounds may be prepared by the following methods: (1) reacting a substituted pyrazinoic acid ester of the Formula II <;FORM:1066855/C2/2>; wherein R* is a C1-alkyl radical with a guanidine of formula <;FORM:1066855/C2/3>; to produce a compound of Formula I; (2) reacting a (3-amino-5,6-dichloropyrazinoyl) guanidine of the Formula III <;FORM:1066855/C2/4>; with an amine of formula RR1NH to produce a compound of Formula IV <;FORM:1066855/C2/5>; (3) reacting a C1-alkyl ester of a 3-amino-5,6-dihalopyrazinoic acid with a saturated alcohol or phenol to produce the corresponding C1-alkyl ester of 3-amino-5-alkoxy- (or aryloxy-)-6-halopyrazinoic acid and reacting the latter with a guanidine of the formula <;FORM:1066855/C2/6>; to produce a compound of Formula V <;FORM:1066855/C2/7>; (4) acylating a compound of Formula VI <;FORM:1066855/C2/8>; with an acid anhydride of the formula (R5CO)2O to produce a 2-alkyl-4H-pyrazino-[2,3-d][1,3]-oxazin-4-one of the Formula VII <;FORM:1066855/C2/9>; and reacting the latter with a guanidine of formula <;FORM:1066855/C2/100>; to produce a compound of the Formula VIII <;FORM:1066855/C2/111>; the N-acyl group of which may be removed by hydrolysis if desired, and (5) catalytic hydrogenolysis of a compound of the Formula IX <;FORM:1066855/C2/122>; where R11 is an alkyl radical, to replace the chlorine atom by hydrogen, brominating the resulting 6-unsubstituted compound to introduce a 6-bromine atom, and reacting the latter with a guanidine of the formula <;FORM:1066855/C2/133>; to produce a compound of the Formula X <;FORM:1066855/C2/144>; The intermediate 3-aminopyrazinoic acid esters may be produced by the methods represented by the following reaction schemes: <;FORM:1066855/C2/155>; <;FORM:1066855/C2/166>; <;FORM:1066855/C2/177>; <;FORM:1066855/C2/188>; <;FORM:1066855/C2/199>; where R in steps (b) and (c) represents a C1- 5 alkyl radical; <;FORM:1066855/C2/200>; <;FORM:1066855/C2/211>; The compounds of Formula VI may be prepared by hydrolysis of the corresponding esters or amides or, for those compounds having a 6-RS or 6-RSO2 group, the method represented by the reaction scheme <;FORM:1066855/C2/222>; where R is a C1 alkyl or a phenyl-substituted C1 alkyl radical. The compounds of Formula III may be prepared by reacting a pyrazinoic acid ester of formula <;FORM:1066855/C2/233>; where R11 is an alkyl radical, with a guanidine of the formula <;FORM:1066855/C2/244>;ALSO:Pyrazinoylguanidines of the general formula I <;FORM:1066855/A5-A6/1>; in which X is a hydrogen a halogen atom, a trihalo-methyl, C1-6 alkyl, C3-6 cycloalkyl, mononuclear aryl, anilino, C1-5 alkylthio, C1-5 alkylsulphonyl, phenyl-substituted C1-5 alkylthio, or phenyl-substituted C1-5 alkylsulphonyl; 7 is a hydrogen or halogen atom or a hydroxyl, mercapto, C1-5 alkoxy, C1-5 alkylthio, C1-6 alkyl, C3-6 cycloalkyl, mononuclear aryl or 4-methyl-1-piperazinyl group or an amino group of the formula -NRR1, where R is a hydrogen atom or an amino, amidino, C3-6 cycloalkyl, C1-6 alkyl, hydroxy-substituted C1-6 alkyl,, halogen-substituted C1-6 alkyl, (C3-6 cycloalkyl)-(C1-5 alkyl), phenyl-substituted C1-5 alkyl, (C1-5 alkyl) phen (C1-5 alkyl), halophenyl substituted C1-5 alkyl, furyl-substituted C1-5 alkyl, pyridyl substituted C1-5 alkyl, C1-5 alkylamino (C1-5 alkyl), C2-6 alkenyl, b -aminoethyl, phenyl, halophenyl or (C1-5 alkyl) phenyl radical and R1 is a hydrogen atom or a C1-6 alkyl or C2-6 alkenyl radical or R and R1 are joined to form a C2-6 alkylene radical, but with the proviso that 7 is not hydrogen when X is hydrogen, halogen or trihalomethyl; or X and Y together form a tetramethylene, 1,3-butadienylene or 2-chloro-1,3-butadienylene radical; Z is an amino, mono-substituted amino, disubstituted amino or heterocyclic amino radical; R2 is a hydrogen atom or a C1-6 alkyl radical; each of R3 and R4 is a hydrogen atom or a C1-6 alkyl, hydroxy-substituted C1-6 alkyl, phenyl-substituted C1-5 alkyl, halophenyl-substituted C1-5 alkyl, (C1-5 alkyl) phen (C1-5 alkyl), (C1-5 alkoxyphenyl) substituted C1-5 alkyl, naphthyl-substituted C1-5 alkyl, (octahydro-1-azocinyl)-substituted C1-5 alkyl, pyridyl-substituted C1-5 alkyl, or phenyl radical; or R3 and R4, together with the nitrogen atom to which they are attached, represent a 1-pyrrolidinyl, piperidino, morpholino, or 4-(C1-4 alkyl)-piperazinyl group and pharmaceutically acceptable salts thereof are employed as duiretic and/or saluretic agents in, for example, pills, tablets, capsules, elixirs, injectable preparations. Other therapeutic agents may be present in the pharmaceutical compositions and when said known therapeutic agents administered alone enhance the elimination of potassium and sodium ions the co-administration of the guaridine of the formula I. Specified known diuretics employed in said pharmaceutical compositions are hydrochlorothiazide; 4\sv-methyl-6-chloro-spiro-[2H-1,2,4-benzothiadiazide-3(4H) -1\sv-cyclohexane] - 7 - sulphonamide-1,1-dioxide; trichloromethiazide; cyclopenthiazide; acetazolamide; dichlorophenamide; chlorthalidone; chlormerodrin; chlorazinil; or spironolactone.

  该发明包括一般式I的化合物，在其中X为氢或卤素原子，三卤甲基，C1-6烷基，C3到C6环烷基，单核芳基，苯胺基，C1-5烷基硫基，C1-5烷基磺酰基，苯基取代的C1-5烷基硫基或苯基取代的C1-5烷基磺酰基；Y为氢或卤素原子或羟基，巯基，C1-5烷氧基，C1-5烷基硫基，C1-6烷基，C3-6环烷基，单核芳基或4-甲基-1-哌嗪基或一般式-NRR1的氨基团，其中R为氢原子或氨基，酰胺基，C3-6环烷基，C1-6烷基，羟基取代的C1-6烷基，卤素取代的C1-6烷基，（C3-6环烷基）-（C1-5烷基），苯基取代的C1-5烷基，（C1-5烷基）苯（C1-5烷基），卤苯基取代的C1-5烷基，呋喃基取代的C1-5烷基，吡啶基取代的C1-5烷基，C1-5烷基氨基（C1-5烷基），C2-6烯基，b-氨乙基，苯基，卤苯基或（C1-5烷基）苯基基团，R1为氢原子或C1-6烷基或C2-6烯基基团或R和R1结合形成C2-6亚烷基基团，但条件是当X为氢，卤素或三卤甲基时，Y不是氢；或X和Y一起形成四亚甲基，1,3-丁二烯亚烷基或2-氯-1,3-丁二烯亚烷基基团；Z为氨基，单取代氨基，双取代氨基或杂环氨基基团；R2为氢原子或C1-6烷基基团；R3和R4中的每一个为氢原子或C1-6烷基，羟基取代的C1-6烷基，苯基取代的C1-5烷基，卤苯基取代的C1-5烷基，（C1-5烷基）苯（C1-5烷基），（C1-5烷氧基苯基）取代的C1-5烷基，萘基取代的C1-5烷基，（八氢-1-氮杂环己基）取代的C1-5烷基，吡啶基取代的C1-5烷基或苯基基团；或R3和R4与它们连接的氮原子一起表示1-吡咯啉基，哌啶基，吗啉基或4-（C1-4烷基）-哌嗪基团及其药学上可接受的盐。这些化合物可以通过以下方法制备：（1）将一般式II的取代吡嗪酸酯（其中R*为C1-烷基基团）与一般式的胍二酰胺反应，以产生一般式I的化合物；（2）将一般式III的（3-氨基-5,6-二氯吡嗪基）胍二酰胺与一般式RR1NH的胺反应，以产生一般式IV的化合物；（3）将3-氨基-5,6-二卤吡嗪酸的C1-烷基酯与饱和醇或酚反应，以产生相应的3-氨基-5-烷氧基（或芳氧基）-6-卤吡嗪酸的C1-烷基酯，并将后者与一般式的胍二酰胺反应，以产生一般式V的化合物；（4）将一般式VI的化合物与一般式（R5CO）2O的酸酐反应，以产生一般式VII的2-烷基-4H-吡嗪-[2,3-d][1,3]-噁唑-4-酮，然后将后者与一般式的胍二酰胺反应，以产生一般式VIII的化合物，其N-酰基如有需要可以通过水解去除；（5）将一般式IX的化合物进行催化氢解，其中R11为烷基基团，以将氯原子替换为氢，溴化所得的6-去取代化合物引入6-溴原子，然后将后者与一般式的胍二酰胺反应，以产生一般式X的化合物。中间体3-氨基吡嗪酸酯可通过以下反应方案制备：其中步骤（b）和（c）中的R代表C1-5烷基基团。一般式VI的化合物可通过对应酯或酰胺的水解制备，对于具有6-RS或6-RSO2基团的化合物，可通过以下反应方案表示的方法制备：其中R为C1烷基或苯基取代的C1烷基基团。一般式III的化合物可通过将一般式的吡嗪酸酯与一般式的胍二酰胺反应制备。此外，一般式I的吡嗪酰胍二酰胺化合物在药物中作为利尿和/或排钠剂，例如在丸剂、片剂、胶囊、口服溶液、注射制剂中使用。药物组合物中可能存在其他治疗剂，当单独使用已知治疗剂增强钾离子和钠离子的排泄时，可联合使用一般式I的胍二酰胺。在所述药物组合物中使用的特定已知利尿剂包括氢氯噻嗪；4-甲基-6-氯-螺[2H-1,2,4-苯并噻二唑-3(4H)-1-环己烷]-7-磺酰胺-1,1-二氧化物；三氯噻嗪；环戊噻嗪；乙酰唑胺；二氯苯胺；氯他醌；氯美酮；氯苄嘧啶；或螺内酮。
• Simple synthesis of 6-methyl-, 3-dimethyl-, 3-methyl-, and 3,7,8-trimethylalloxazine.
  作者：Danuta Panek-Janc、Jacek Kozioł

  DOI：10.1016/s0040-4039(01)86520-5

  日期：1979.1
• Substituted Sulfaquinoxalines. II. Some Derivatives and Isomers of 2-Sulfanilamidoquinoxaline¹
  作者：F. J. Wolf、R. H. Beutel、J. R. Stevens

  DOI：10.1021/ja01187a082

  日期：1948.7
• 8-Chloroalloxazine, A New Diuretic. Synthesis and Structure
  作者：HAROLD G. PETERING、GARRETT J. VAN GIESSEN

  DOI：10.1021/jo01066a047

  日期：1961.8