Unexpected formation of a 11H-pyrido[2,1-b]quinazolin-11-one derivative from 5,11-dihydro-6H-pyrido[2,3-b]-1,4-benzodiazepin-6-one

The unexpected formation of 11H-pyrido[2,1-b]quinazolin-11-one derivative 6 from 5,11-dihydro-6H-pyrido[2,3-b]-1,4-benzodiazepin-6-one (2) has been observed. Its structure 6 was determined by X-ray crystallography. Detailed nmr study provided a complete set of proton and carbon-13 nmr parameters of compound 6 in solution.     

苯并咪唑并[2,1-b]噻唑衍生物的合成

以2-巯基咪唑类化合物为原料,室温下与含有端基炔的二芳基高碘盐反应,一步合成苯并咪唑并[2,1-b]噻唑衍生物,其结构经¹H NMR、¹³C NMR、 单晶X-衍射和HR-MS表征。在最佳反应条件［n(2-巯基苯并咪唑)/n(二芳基高碘盐)=1/1,二氯甲烷为溶剂,反应12 h］下,目标化合物的产率最高为84%。同时对该反应的机理进行了详细探讨,并采用MTT法研究了目标化合物对人肝癌细胞（HepG2）生长情况的影响。结果表明：当浓度为4 μg/mL时,化合物3b具有较强的抑制HepG2细胞增殖的活性,抑制率为52%。     

A Facile and Efficient Synthesis of Novel 1,2,4-Triazolo[5,1-b]quinazolin-9-one Derivatives

Summary.  A facile and efficient synthesis of a series of novel 1,2,4-triazolo[5,1-b]quinazolines is described. 2,3-Diaryl-2,3-dihydro-1H-1,2,4-triazolo[5,1-b]quinazolin-9-ones were obtained by reaction of 3-amino-2-arylamino-3H-quinazolin-4-ones with aromatic aldehydes as well as by ring closure of the corresponding anils. Treatment of 3-amino-2-arylamino-3H-quinazolin-4-ones with aromatic carboxylic acids afforded 2,3-diaryl-3H-1,2,4-triazolo[5,1-b]quinazolin-9-ones which could also be synthesized by dehydrogenation of the corresponding dihydro derivatives. Reaction of 3-amino-2-arylamino-3H-quinazolin-4-ones with diethyl malonate and acetylacetone gave 3-aryl-3,9-dihydro-9-oxo-1,2,4-triazolo[5,1-b]quinazolin-2-yl-acetic acid ethyl ester and 3-aryl-2-methyl-3H-1,2,4-triazolo[5,1-b]quinazolin-9-ones, respectively. The latter compounds were also prepared via reaction with acetic anhydride, whereas acetylation with acetic anhydride in the presence of pyridine afforded the acetyl derivatives. Received March 22, 2001. Accepted (revised) May 11, 2001     

纳米TiO_2催化一锅法合成喹唑啉酮并酞嗪酮及3-酰胺基异吲哚酮并喹唑啉酮类化合物

以纳米TiO_2为催化剂,靛红酸酐、2-甲酰基苯甲酸、不同芳香肼或酰肼类化合物为原料,在乙醇/水溶液为溶剂的条件下一锅法合成,高产率得到6个喹唑啉酮并酞嗪酮类化合物及10个3-酰胺基取代的异吲哚酮并喹唑啉酮类化合物.该方法简洁高效,反应条件温和,为喹唑啉酮并杂环类化合物的合成提供了一条新途径.     

Nitrogen bridgehead compounds. Part 45 [1]. Synthesis of 6-arylhydrazono-6,7,8,9-tetrahydro-11H-pyrido-[2,1-b]quinazolin-11-ones

A series of 6-arylhydrazono-6,7,8,9-tetrahydro-11H-pyrido[2,1-b]quinazolin-11-ones 3–37 , conveneint starting materials for indolopyridoquinazolines, were prepared by diazonium coupling between aryldiazonium chlorides and 6,7,8,9-tetrahydro- 2 , 6-formyl-5,7,8,9-tetrahydro- 39 , 6-(dimethylamino)methylene-6,7,8,9- 38 or 6-carboxyl-5,7,8,9-tetrahydro-11H-pyrido[2,1-b]quinazolin-11-ones 43 . The arylhydrazono derivatives were also prepared from 6-bromo- 45 or 6,6-dibromo-6,7,8,9-tetrahydro-11H-pyrido[2,1-b]quinazolines 46 with arylhydrazines. The structures of the 6-arylhydrazonopyridoquinazolines were characterized by uv and ¹H nmr spectroscopy. The 6-arylhydrazono derivatives show a solvent-dependent E-Z isomerism.     

Synthesis of Pyrrolo[2,1-b]thiazol-3-one Derivatives

Ethyl [4-oxo-3-(2-oxo-2-arylethyl)thiazolidin-2-ylidene]acetates and [4-oxo-3-(2-oxo-2-arylethyl)thiazolidin-2-ylidene]acetonitriles were shown to react with substituted benzaldehydes at the endocyclic methylene group leading to the corresponding 5-arylmethylidene derivatives. Their treatment with DMF · POCl₃ complex yielded 3-oxo-5-aroyl-2-arylmethylidene-2,3-dihydropyrrolo[2,1-b]thiazole-7-carboxylic acids ethyl esters and -7-carbonitriles. The structures of the pyrrolothiazoles were confirmed by an X-ray crystallographic study, which indicated the (Z)-configuration at the arylmethylidene moiety.     

1H and 13C spectral assignment of substituted 5H-[1,3]thiazolo[2,3-b]quinazolin-5-one and 12H-[1,3]benzothiazolo[2,3-b] quinazolin-12-one

(1)H and (13)C spectroscopic data for 5H-[1,3]thiazolo[2,3-b]quinazolin-5-one and 12H-[1,3]benzothiazolo[2,3-b]quinazolin-12-one derivatives were fully assigned by combination of one- and two-dimensional experiments (DEPT, HMBC and HMQC). Both heterocyclic systems show similar spectroscopic properties with some remarkable differences.     

Synthesis and Structure Elucidation of Pyrimidobenzimidazoles and Fused Derivatives II [1]. Dodecahydrobenzimidazo-[2,1-b]quinazolines and Decahydrobenzimidazo-[2,1-b]benzo[h]quinazolines [2]

Summary.  The cyclization reactions of trans-3a-hexahydro-2-benzimidazolamine with 2-alkylidene- and 2-benzylidenecyclohexanones and α-tetralones, respectively, yield mixtures of two isomeric condensates each. Thorough high resolution NMR analyses (¹H and ¹³C NMR, HH-COSY, gs-HSQC, gs-HMBC, 1D TOCSY, and 1D NOE difference spectra) revealed that the corresponding isomers are in all cases linearly fused diastereomeric 12α- and 12β-substituted trans-6aα-dodecahydrobenzimidazo[2,1-b]quinazolines and 7α-substituted trans-8aβ- and trans-8aα-decahydrobenzimidazo[2,1-b]benzo[h]quinazolines, respectively. The formation of corresponding angularly fused regioisomers was not observed so far. The stereochemistry and the tautomerism of some bases and their hydrochlorides as well as the regiospecific course of the cyclization reactions are discussed. Biological tests showed that the novel compounds don’t exert remarkable antibacterial and antimycotic effects. Received November 3, 1999. Accepted November 30, 1999     

Pseudopolymorphism and phase stability of 7-piperidino-1,2,3,5-tetrahydroimidazo-[2,1-b]quinazolin-2-one (DN-9693)

The phase stabilities of three pseudopolymorphs of DN-9693 were studied by using thermogravimetry and differential thermal analysis. The thermal dehydration of DN-9693·2HCl·H₂O proceeds by the mechanism of two-dimensional growth of nuclei. The thermal dehydration of 0.5 mol of H₂O per mol of DN-9693·2HCl·2H₂O, and that of 2 mol of H₂O per mol of DN-9693·2HCl·3H₂O, proceed by the mechanisms of three-dimensional diffusion and three-dimensional phase boundary reaction, respectively, but the dehydration followed overlaps with the thermal elimination of HCl. The half-lives for the dehydration at 25°C show that DN-9693·2HCl·H₂O is the most stable form.     

Synthesis of tetrahydrobenzimidazo[1,2-b]quinazolin-1(2H)-one and tetrahydro-1,2,4-triazolo[5,1-b]quinazolin-8(4H)-one ring systems under solvent-free conditions

Tetraheterocyclic benzimidazo[1,2-a]quinazolin-4(1H)-one and tetrahydro-1,2,4-triazolo[5,1-b]quinazolin-8(4H)-one were synthesized in relatively high yields by the condensation reaction of an aldehyde and a cyclic beta-diketone with 2-aminobenzothiazole, 2-aminobenzimidazole or 3-amino-1,2,4-triazole without using any catalyst under solvent-free conditions.     

2,1-benzisothiazoles. XIII. Intermediates and products in the sulfur extrusion reaction of 2,1-benzisothiazolin-3(1H)-one. A new synthesis of 11H-pyrido[2,1-b]quinazolin-11-one (“pyracridone”)

Triethyl phosphite abstracts sulfur from 2,1-benzisothiazolin-3(1H)-one (1); a reaction intermediate is the spirocyclic compound 11 , and products include the benzoxazine 6 and polyanthraniloyl compounds. In the presence of pyridine, pyracridone ( 13 ) is formed. The ketene-imine 9 is probably not an intermediate in these reactions. The reactions of other nucleophiles with 1 and with its N-methyl derivative 15 , have been examined.     

Synthesis of pyrido[2,1-b]- and thiazolo[2,3-b]purines

Some pyrido[2,1-b]- and thiazolo[2,3-b]purines, tricyclic compounds structurally related to [1,2,4]triazolo[1,5-c]quinazolines 1 have been synthesized with a view to study their possible adenosine and benzodiazepine receptors affinity.     

High Throughput Synthesis of 2,3,6-Trisubstituted-5,6-Dihydroimidazo[2,1-b]thiazole Derivatives

A facile approach to the synthesis of 2,3,6-trisubstituted-5,6-dihydroimidazo[2,1-b]thiazole was reported. A resin bound cyclic thiourea was formed by the treatment of a resin bound diamine with 1,1′-thiocarbonyldiimidazole, and then reacted with a α-haloketone to generate a resin bound isothiourea. HF treatment of the resin bound isothiourea resulted in the cleavage of the product and simultaneous formation of an enamine bond. This led to the formation of the 2,3,6-trisubstituted-5,6-dihydroimidazo[2,1-b]thiazole in high yield and purity.     

Synthesis of Naphtho[2,1-b]pyrano Pyrrolothiazole Derivatives through 1,3-Cycloaddition Reaction

Facile synthesis of a series of naphtho[2,1,b]pyrano pyrrolo thiazoles was accomplished in good yields in a one-pot reaction through intramolecular 1,3-dipolar cycloaddition of cyclic azomethine ylides with Baylis–Hillman adducts as dipolarophiles. The protocol is applicable to a wide variety of photochromic and biologically active napthopyrano products. The regio- and stereochemical outcome of the cycloaddition reaction was ascertained by x-ray crystallographic study of one of the cycloadducts.     

含有异(口恶)唑的S-三唑[3,4-b]-1,3,4-噻二嗪、咪唑[2,1-b]-1,3,4-噻二唑和咪唑[2,1-b]-1,3,4-(口恶)二唑衍生物的合成

异噁唑衍生物作为一类重要的生物活性物质[1,2],其合成一直受到人们的关注,其中德国HMR公司开发研制的新型抗内风湿性关节炎药来氟米特(Leftunomide)已于1998年在美国率先上市,该药还具有很好的免疫调节作用[3].7H-均三唑[3,4-b]-1,3,4-噻二嗪、咪唑并[2,1-b]噻唑和咪唑并[2,1-b]-1,3,4-噻二唑衍生物均表现出广谱的生物活性[4～6].     

1,3,4-均三唑并[2,1-b]-1,3,4-噻二唑衍生物的合成及生物活性

以5-对甲苯基-1-氨基-2-巯基-1,3,4-均三唑和取代苯氧乙酰异硫氰酸酯为原料, 合成了10个未见文献报道的5-对甲苯基-2-取代苯氧乙酰氨基均三唑并[2,1-b]-1,3,4-噻二唑类化合物, 通过元素分析, 1H NMR, IR和MS确定化合物的结构, 初步生物活性测试表明目标化合物具有较好的除草活性.     

Synthesis and Reaction of Some Indenopyridine and Thieno[2,3-b]Indeno[2,1-e]Pyridine Derivatives

Synthesis of indenopyridine-2-thione derivatives 6a-e via reaction of compound 1 with thioamides 2a-e in good yields. Several thieno[2,3-b]indeno[2,1-e]pyridine 9a-e have been synthesized. Some of them was used as a key intermediate in synthesis of 10-12. On the other hand, compound 1 reacted with various reagents to yield 16, 19, 21-24.