Untersuchungen über die Reaktion von N-Isopropyl-N′-phenylcarbodiimid mit Benzoylchlorid,Oxalsäuredichlorid und Quadratsäuredichlorid

Reactions of N-Isopropyl-N′-phenylcarbodiimide with the Chlorides of Benzoic, Oxalic, and Squaric Acid The structures of the addition products of N-isopropyl-N′-phenylcarbodiimide ( 1 ) and benzoyl chloride or squaric acid dichloride were elucidated by spectroscopic comparison with reference compounds.     

Synthese und Eigenschaften des 3-Hydroxy-1,10-dioxo-5,10-dihydro-1H-pyrido[2,1-b]chinazolin-2-carbonitrils

Synthesis and Properties of 3-Hydroxy-1,10-dioxo-5,10-dihydro-1H-pyrido[2,1-b]quinazoline-2-carbonitrile Anthranilic acid reacts with 2-chloro-5-cyano-4-hydroxypyrid-6-one (3) in glacial acetic acid to yield 3-hydroxy-1,10-dioxo-5,10-dihydro-1H-pyrido[2,1-b]quinazoline-2-carbonitrile (4) . When the reaction is carried out in DMF under Ullmann conditions, 2-(dimethylamino)-5-cyano-4-hydroxypyrid-6-one (5) forms as a by-product. The methylation of 3 with diazomethane affords 2-chloro-5-cyano-2-methoxy-N-methylpyrid-6-one (9) and 2-chloro-5-cynao-4,6-dimethoxypyridine (10) . Under similar conditions compound 4 undergoes an esterifying ring cleavage to furnish methyl 2-(5-cyano-4,6-dimethoxypyrid-2-ylamino)benzoate (7) .     

Polycarbonylverbindungen, 19. Mitt. Synthese und Solvolysereaktionen tosylsubstituierter Quadratsäurebisamidine

Polycarbonyl Compounds, IXX: Synthesis and Solvolysis Reactions of N-Tosyl Squaric Acid Bisamidines N-Tosyl squaric acid bisamidines were synthesized by the reaction of squaric acid 1,2- and 1,3-diamides 5 and 6 or of their thio analogues 9 and 10 with excess p-tosyl isocyanate ( 4 ). Hydrolysis, sulfhydrolysis and aminolysis of the products are described.     

Synthesis of [1,2,4]triazolo[3′,4′:3,4][1,2,4]triazino[5,6-b]indole,tetrazolo[5′,1′:3,4][1,2,4]triazino[5,6-b]indole and their Derivatives

Reactions of 5-ethyl 5H-1,2,4-triazino|5,6-b|indol-3-thione ( 1 ) with various reagents have been studied. 1 and hydrazine hydrate in anhydrous ethanol gave 5-ethyl-3-hydrazino-5H-1,2,4-triazino|5,6-b|indole ( 2 ). This compound was condensed with formic acid and acetic acid to give 10-ethyl-10H-|1,2,4|triazolo|3′,4′:3,4||1,2,4|triazino|5,6-b|indole ( 4 , R=H) and 10-ethyl-1 -methyl-10H-|1,2,4|triazolo-|3′,4′:3,4‖ 1,2,4|triazino|5,6-b|indole ( 4 , R = CH₃), respectively. Treatment of 2 with nitrous acid gave 10-ethyl-10H-tetrazolo|5′,1′:3,4‖ 1,2,4|triazino|5,6-b|indole ( 7 ). Interaction of 2 with acetylacetone in alcoholic KOH gave the pyrazole 8 , whereas reaction of 2 with ethyl acetoacetate in anhydrous ethanol led to the expected hydrazone 9 , which on reflux with alcoholic KOH gives 1-(5-ethyl-5H-1,2,4-triazino| 5,6-b|indol-3-yl)-3-methyl-2-pyrazolin-5-one 10 . Treatment of 2 with ethyl chloroformate gives 11 , which can be converted to 10-ethyl-2,10-dihydro-1H-|1,2,4|triazolo|3′,4′:3,4|triazino|5,6-b|-indol-1-one 12 by fusion.     

Aromatic glycosides from the flower buds of Lonicera japonica

Six new glycosides (1–6) have been isolated from the flower buds of Lonicera japonica. Their structures including the absolute configurations were determined by spectroscopic and chemical methods as ( ? )-2-hydroxy-5-methoxybenzoic acid 2-O-β-d-(6-O-benzoyl)-glucopyranoside (1), ( ? )-4-hydroxy-3,5-dimethoxybenzoic acid 4-O-β-d-(6-O-benzoyl)-glucopyranoside (2), ( ? )-(E)-3,5-dimethoxyphenylpropenoic acid 4-O-β-d-(6-O-benzoyl)-glucopyranoside (3), ( ? )-(7S,8R)-(4-hydroxyphenylglycerol 9-O-β-d-[6-O-(E)-4-hydroxy-3,5-dimethoxyphenylpropenoyl]-glucopyranoside (4), ( ? )-(7S,8R)-(4-hydroxy-3-methoxyphenylglycerol 9-O-β-d-[6-O-(E)-4-hydroxy-3,5-dimethoxyphenylpropenoyl]-glucopyranoside (5), and ( ? )-4-hydroxy-3-methoxyphenol β-d-{6-O-[4-O-(7S,8R)-(4-hydroxy-3-methoxyphenylglycerol-8-yl)-3-methoxybenzoyl]}-glucopyranoside (6), respectively.     

Two novel A-<Emphasis Type="Italic">seco</Emphasis>-rearranged lanostane triterpenoids from <Emphasis Type="Italic">Abies sachalinensis</Emphasis>

Further chemical study led to two new A-seco-rearranged lanostane triterpenoid derivatives (1–2) and one known compound Abiesanolide C (3) from the ethyl acetate (EtOAc) soluble fraction of the MeOH extract of Abies sachalinensis needles. The new compounds were identified as 3,4-seco-8-(14→13R)abeo-17,13-friedo-9β-lanosta-4(28), 7, 14, 24-tetraen-26,23-olide-23-hydroxy-3-oic acid and methyl-3,4-seco-8-(14→13R) abeo-17,13-friedo-9β-lanosta-4(28), 7, 14, 24-tetraen-26,23-olide-23-hydroxy-3-oate, respectively. Structural determination of these compounds were carried out by the spectral studies especially by the two digital (2D)-NMR and high-resolution (HR)-MS experiences.     

The Effective Synthesis of N-(Arylalkyl)-1-R-4-hydroxy-2,2-dioxo- 1H-2λ6,1-benzothiazine-3-carboxamides as Promising Analgesics of a New Chemical Class

A new, effective preparative method has been proposed and the synthesis of a series of N-(arylalkyl)-1-R-4-hydroxy-2,2-dioxo-1H-2λ⁶,1-benzothiazine-3-car-boxamides has been carried out. It has been shown that amidation of alkyl 1-R-4-hydroxy-2,2-dioxo-1H-2λ⁶,1-benzothiazine-3-carboxylates with arylalkyl-amines in boiling xylene proceeds with good yield and purity to the corresponding N-(arylalkyl)-amides. However, the presence of water in the reaction mixture has been shown to cause the formation of specific impurities: N-(arylalkyl)-1-R-2,2-dioxo-1H-2λ⁶,1-benzothiazin-4-amines. According to the results of the pharmacological studies, powerful analgesics have been found among the substances synthesized.     

N-Phenylcarbamoyloxy-isopropylamin: Bildungsmöglichkeit durch Isomerisierung und authentische Synthesen

1-Methyl-N-(phenylaminocarbonyloxy)ethanamine: Authentic Syntheses and Possible Formation by Isomerisation The title compound 2a was synthesized by two authentic methods, and used as reference substance in the investigation of its possible formation in the thermically induced isomerization of N-hydroxy-N-isopropyl-N'-'-phenylurea ( la ).     

Umsetzungen von Quadratsäurediäthylester und Quadratsäure mit Enaminen

Reactions of Squaric Acid with Enamines Reaction of 1,2-bisethoxy-cyclobutene-dione-(3,4) with enamines leads to 1 + 1-compounds. By acid hydrolysis 1-ethoxy-2(cyclan-2-on-yl)-cyclobutene-diones-(3,4). The reaction between squaric acid and enamines leads to 1,3-bisamino-cyclobutene-diones-(3,4) or to 1-amino-2-hydroxy-cyclobutene-diones-(3,4).     

Photo- und strahlenchemische Studien, 46. Mitt. Zur Photochemie des Isopropylaminophenazons im kristallinen Zustand und in wäßriger Lösung

Photochemical Studies, XLVI: Photochemistry of Isopropylaminophenazone in the Solid State and in Aqueous Solution Photolysis of 4-(isopropylamino)-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one (isopropylaminophenazone) ( 1 ) in the solid state (A) or in aqueous solution (B) leads to: (A) N-isopropyl-N′-phenyloxamide, N′-acetyl-N′-methyl-N-(isopropylaminooxalyl)phenylhydrazine ( 2 ) and 2-(isopropylimino)-3-(methylimino)butyric acid anilide ( 3 ); (B) methyltartronic acid anilide isopropylamide ( 4 ), methyltartronic acid anilide methylamide ( 5 ), N-phenyl-N-(2-methylaminopropionyl)carbamic acid ( 6 ) and isopropylamine. The rearrangement of 1 to 3 is the first example of a solid state photoisomerisation in a 3-pyrazolin-5-one derivative.     

Synthesis of N‐(2‐chloro‐3,4‐dimethoxybenzylideneamino)guanidinium acetate [α‐14C]

¹⁴C‐Labelled N‐(2‐chloro‐3,4‐dimethoxybenzylideneamino)guanidinium acetate has been synthesized as a part of a four‐step procedure which involved decarboxylation of 2‐chloro‐3,4‐dimethoxybenzoic acid by Pb(OAc)₄ to give 2‐chloro‐3,4‐dimethoxy‐1‐iodobenzene, followed by a selective lithiation at the iodine position and electrophilic substitution with N,N‐dimethylformamide [α‐¹⁴C] and final reaction with aminoguanidine bicarbonate. The specific activity was 59 mCi/mmol and the overall yield 49%. Copyright © 2002 John Wiley & Sons, Ltd.     

Reaktionen von 2-Amino-imidazo[2,1-b]-1,3,4-thiadiazolen mit Dicarbonsäureestern in Polyphosphorsäure (PPA)

Reactions of 2-Aminoimidazo[2,1-b]-1,3,4-thiazoles with Ethyl Dicarboxylates in Polyphosphoric Acid (PPA) The 2-amino-6-arylimidazo[2,1-b]-1,3,4-thiadiazoles 1d,e cyclise on heating in polyphosphoric acid (PPA) with ethyl malonate or ethyl diethylmalonate to yield the 2-aryl-6,8-dioxodihydro-6H-imidazo[2,1-b]-1,3,4-thiadiazolo[3,2-a] pyrimidines 3d,e or the 7,7-diethyl compounds 4d,e . Compounds 1a – f cyclise in PPA with ethyl succinate or ethyl phthalate to yield the 6-aryl-2-succinimido- or 6-aryl-2-phthalimido-imidazo[2,1-b]-1,3,4-thiadiazoles 5a, b, d-f and 6a – f . Compounds 1d,e were condensed with ethyl oxalate to yield the 2-(ethoxycarbonyl-formylamino)-6-arylimidazo[2,1-b]-1,3,4-thiadiazoles 7d,e. Ethyl levulinate with 1d,e in PPA probably forms 6-aryl-2-(2-methyl-5-oxo-Δ³-pyrrolino)imidazo [2,1-b]-1,3,4-thiadiazoles.     

Reaktionen an Heterocyclen mit 2-Acyl-2-propenon-Teilstruktur, 4. Mitt. Synthese von Pyridinderivaten aus 4-Hydroxy-2-oxo-2H-chromen-3-carboxaldehyden und Enaminen

Reactions of Heterocycles Containing the 2-Acyl-2-propenone Structure, IV: Synthesis of Pyridine Derivatives from 4-Hydroxy-2-oxo-2H-chromene-3-carbaldehydes and Enamines The reactivities of 4-hydroxy-2-oxo-2H-chromene-3-carbaldehydes 2 toward a variety of enamines (3-6) are investigated. Depending on the structure of the enamine, reactions with 2 result in the formation of derivatives of pyrido[3,4-c]coumarine (16) or of 3-(2-hydroxybenzoyl)-2H-pyridone (20–22) .     

Species differences in the in vitro metabolism of methapyrilene

1. The metabolism of N, N-dimethyl-N'-(2-pyridyl)-N'-(2-thienylmethyl)-1,2- ethanediamine(methapyrilene, I) by liver microsomes from rat, guinea pig, and rabbit has been examined.

2. Methapyrilene-N-oxide, (III), normethapyrilene, (II), 2-thiophene methanol, (VI), 2-thiophene carboxylic acid, (VII), N-(2-pyridyl)-N',N'-dimethylethylenediamine, (IX), and methapyrilene amide, (XIV) were found in all species.

3. N-(2-Thienylmethyl)-2-amino pyridine, (VIII), 2-aminopyridine, (X), and (5-hydroxypridyl)-methapyrilene, (XII), were detected in rat and rabbit only.

4. N-Hydroxynormethapyrilene, (XXI), was tentatively identified by mass spectral fragmentation patterns only in rabbit liver microsomes incubations; however, it was found in 9000?g supernatant fraction incubations of rabbit, rat and guinea pig.

5. The formation of IX and XII was quantitatively more important in the rat than in either rabbit or guinea pig.     

Syntheses of Potentially Antineoplastic Amides and Esters of N-[N'-(2-Chloroethyl)-N'-nitrosocarbamoyl]amino Acids,II

Syntheses of N-[N'-(2-chloroethyl)-N'-nitrosocarbamoyl]amino acid amides and esters as potential antineoplastic substances are reported. N-[N'-(2-chloroethyl)-N'-nitrosocarbamoyl]amino acids (with the exception of the glycine derivative) were prepared by reaction of 2-chloroethyl isocyanate with the sodium salt of an amino acid in a heterogenous medium followed by nitrosation with sodium nitrite under acidic conditions. Condensation with amines or alcohols using 1,1-carbonyldiimidazole led to the amides or esters.     

Lignans from the stems of Sambucus williamsii and their effects on osteoblastic UMR106 cells

Three new lignans, sambucunol A (8) ((+)-erythro-1-(4-hydroxy-3-methoxyphenyl)-2-[4-(4-hydroxy-3-methoxycinnamoyloxypropanyl)-2-hydroxyphenoxy]-1, 3-propanediol), sambucunol B (9) ((+)-threo-1-(4-hydroxyl-3-methoxyphenyl)-2-[4-(4-hydroxy-3-methoxy-cinnamoyloxy propanyl)-2-hydroxyphenoxy]-1, 3-propanediol) and buddlenol G (10) (2-{4-[2, 3-dihydro-3-hydroxymethyl-7-hydroxy-5-(4-hydroxy-3-methoxycinnamoyloxypropanyl)-2-benzofuranyl]-2,6-dimethoxyphenoxy}-1-(4- hydroxy-3-methoxyphenyl) -1, 3-propanediol), along with seven known ones, including ( ? )-syringaresinol (1), ( ? )-pinoresinol (2), 1, 2-bis(4-hydroxy-3-methoxy phenyl)-1, 3-propanediol (3), ( ? )-erythro-1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-hydroxy propanyl)-2-methoxyphenoxy]-1, 3-propanediol (4), ( ? )-threo-1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-hydroxypropanyl)-2-methoxy phenoxy]-1, 3-propanediol (5), ( ? )-lariciresinol (6) and ( ? )-dihydrodehydrodiconiferyl alcohol (7), were isolated from the 60% ethanol extract of stems of Sambucus williamsii Hance by chromatographic methods. Their structures were established by spectral analysis. The effects of isolated compounds on the osteoblast-like UMR106 cell proliferation and ALP activities were determined. Compounds 2, 7 and 10 showed stimulating effects both on UMR106 cell proliferation and ALP activity. Compounds 1, 3, 6 and 8 stimulated UMR106 cell proliferation, while compounds 4 and 5 induced ALP activity in UMR106 cell.     

Synthesis and antiviral activity of new 4-(phenylamino)/4-[(methylpyridin-2-yl)amino]-1-phenyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acids derivatives

The synthesis of new 4-(phenylamino)-1-phenyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid (3a-l) derivatives and the new 4-[(methylpyridin-2-yl)amino]-1-phenyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid (5a–c) derivatives was achieved with an efficient synthetic route. Ethyl 4-chloro-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylate (1) on fusion with appropriate substituted anilines or aminopicolines gave the required new ethyl 4-(phenylamino)-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylates (2a–l) (52–82%) or new ethyl 4-[(methylpyridin-2-yl)amino]-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylates (4a–c) (50–60%), respectively. Subsequent hydrolysis of the esters afforded the corresponding carboxylic acids (3a–l) (86–93%) and (5a–c) in high yield (80–93%). Inhibitory effects of 4-(phenylamino)/4-[(methylpyridin-2-yl)amino]-1-phenyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acids. Derivatives on Herpes simplex virus type 1 (HSV-1), Mayaro virus (MAY) and vesicular stomatitis virus (VSV) were investigated. Compounds 2d, 3f, 3a, and 3c exhibited antiviral activity against HSV-1, MAY, and VSV virus with EC₅₀ values of 6.8, 2.2, 4.8, 0.52, 2.5, and 1.0. None of these compounds showed toxicity for Vero cells.     

N6-苯甲酰基-2'-叔丁基二甲基硅氧基腺苷-3'-H-膦酸的合成工艺研究

目的 研究N~6-苯甲酰基-2′-叔丁基二甲基硅氧基腺苷-3′-H-膦酸的合成工艺。方法 以腺苷为起始原料,先对腺苷的嘌呤氨基进行苯甲酰基保护,再分别向腺苷的5′位和2′位引入二甲氧基三苯甲基(DMT)和叔丁基二甲基硅基(TBDMS)保护基,制备得到关键中间体N~6-苯甲酰基-5′-二甲氧基三苯甲氧基-2′-叔丁基二甲基硅氧基腺苷(3)。中间体3与磷试剂2-氯-4H-1,3,2-苯并二氧磷杂环己烷-4-酮反应引入膦酸基团,最后使用二氯乙酸脱除DMT保护基得到目标产物。结果 经过5步反应得到了目标化合物N~6-苯甲酰基-2′-叔丁基二甲基硅氧基腺苷-3′-H-膦酸,并利用~1H-NMR、~(31)P-NMR、质谱等方法确证了其结构。本合成工艺的总收率为35.7%,目标化合物的质量分数为98.5%。结论 该合成工艺与原有方法相比步骤短,操作简单,具有良好的应用前景。     

Derivate des 2-Amino-1,2,3,4-tetrahydronaphthalins,III. Synthese einiger N'-substituierter N-(trans-3-Hydroxy-1,2,3,4-tetrahydro-2-naphthyl)-piperazine

Derivatives of 2-Amino-1,2,3,4-tetrahydronaphthalene, III: Synthesis of Some N'-Substituted N-(trans-3-Hydroxy-1,2,3,4-tetrahydro-2-naphthyl)piperazines The synthesis of the N'-substituted N-(trans-3-hydroxy-1,2,3,4-tetrahydro-2-naphthyl)piperazines 2 – 5 and of trans-2-morpholino-3-hydroxy-1,2,3,4-tetrahydronaphthalene ( 6 ), starting from 2,3-epoxytetralins 1 , is reported. The new Mannich bases 3 show hypotensive and antiarrhythmic activities.     

Beiträge zur Chemie des Pyridazinsystems, 34. Mitt.: Synthese neuer Diaza-Analoga des Acridons,Xanthons und Thioxanthons aus 3,4-disubstituierten Pyridazinen

Pyridazine Chemistry XXXIV^{1, 2)}: Synthesis of Novel Diaza Analogues of Acridone, Xanthone and Thioxanthone from 3,4-Disubstituted Pyridazines. Reactions of 3-chloropyridazine-4-carbonitrile 5 with arylamines, phenol or thiophenol, followed by PPA promoted cyclisation, provide access to the new tricyclic systems pyridazinol 3,4-b|quinolin-5(10H)one,5H-|1|benzopyrano|2,3-c|pyridazin-5-one and 5H-|1|benzothiopyrano|2,3-c|pyridazin-5-one.