Pyrazines Pyrazoles

Hydroxy group of 8-hyd oxy-2-cycloalkyl-2,3,4,6,ll,lla-hexahydro-l//-pyrazino[l,2-i]isoquinoline-l,4-diones was alkylated with allyl bromide, 2-(bromodifluoromethyl)pyridines, l-(bromodifluoromethyl)- and l-(bro-momethyl)benzenes, halomethyl derivatives of different heterocycles (pyridine, pyrazine, pyrazole, pyrrole, thiazole, thiophene) in the presence of CS2CO3 or K2CO3 (98MIP7). Hydroxy group of 8-hydroxy-2-cyclopentyl-... 

B—1) Special products such as for instance thiadiazoles, isoxazo-les, pyridazinones, pyrazines, pyrazoles, etc. 

An interesting challenge to Vanquickenborne s model of regiospecific labilization has been presented by Muir and co-workers,746 who studied the photoinduced amine aquation from complexes of the form tra .v-[RhL4Cl2]+ where L is a heterocyclic amine (pyrazine, pyrazole, pyridine, imidazole, and substituted analogs). Unlike the ammine and ethylenediamine analogs, where chloride loss dominates, both amine and chloride are stereoretentively labilized from these com-... 

Keywords Azepines Benzimidazoles Benzofurans Benzopyranones Benzothlazoles Benzothiophenes Benzoxazoles Benzoxocanes DIoxepanes Dioxocanes DIoxolanes Dithiiranes Dithioles Furans Imidazoles Indazoles Indoles Indollnes Indollzines Isoquinolines Isoxazoles Isoxazolines Oxazines Oxazoles Oxepanes Oxiranes Pyrazines Pyrazoles Pyridazines Pyridines Pyrimidines Pyrroles Pyrrolidines Pyrrolines Pyrrolizines Quinolines Thietanes Thiophenes Triazoles... 

Some hydrazinium salts of organic acids like pyrazine, pyrazole, and imidazole carboxylates discussed in Chapter 2 have proved useful as antibacterial agents. The in vitro antibacterial screening of the free acids and their hydrazinium salts has been carried out against Escherichia coli. Salmonella iyphi, and Vibrio cholerae, the results of which are presented here [41]. 

Premkumar, T. (2002) Synthesis and structural, spectroscopic, and thermal characterization of pyrazine, pyrazole and imidazole carboxylates of metal with hydrazine, Ph.D Thesis, Bharathiar University, Coimbatore, India. 

H,3H- Pyrrolo[l, 2-c]oxazole-l, 3-dione, 5,6,7,8-tetrahydro-IR spectra, 6, 978 [2.2](2,5)Pyrrolophane, N-aryl-rearrangements, 4, 209 Pyrrolophanes natural products, 7, 764 synthesis, 7, 771 Pyrrolophanes, N-aryl-synthesis, 7, 774 (2,4)Pyrrolophanes synthesis, 7, 771 Pyrrolo[3,4-c]pyran-4-ones synthesis, 4, 288 Pyrrolopyrans synthesis, 4, 525, 526 Pyrrolopyrazines synthesis, 4, 526 Pyrrolo[l, 2-a]pyrazines synthesis, 4, 516 Pyrrolo[2,3-6]pyrazines Mannich reaction, 4, 504 Vilsmeier reaction, 4, 505 Pyrrolo[3,4-c]pyrazole, 1,3a,6,6a-tetrahydro-structure, 6, 976 synthesis, 6, 1019 Pyrrolopyrazoles synthesis, 5, 164 Pyrrolo[l,2-6]pyrazoles synthesis, 6, 1002, 1006 Pyrrolo[3,4-c]pyrazoles reactions, 6, 1034 synthesis, 6, 989, 1043 Pyrrolo[3,4-c]pyrazolones synthesis, 6, 989 Pyrfolopyridazines synthesis, 4, 517 Pyrrolo[l, 2-6]pyridazines synthesis, 4, 297 6/7-Pyrrolo[2,3-d]pyridazines synthesis, 4, 291 2/f-Pyrrolo[3,4-d]pyridazines synthesis, 4, 291 6/7-Pyrrolo[3,4-d]pyridazines synthesis, 4, 291... 

Thieno[3,4-d]oxazole-3a(4H)-carboxylic acid, dihydro-2-methyl-synthesis, 6, 1020 Thieno[2,3-d Joxazoles synthesis, 6, 990 Thieno[3,2-g]pteridine structure, 3, 284 lH-Thieno[3,4-c]pyran-2-ones synthesis, 4, 1032 Thienopyrazines synthesis, 4, 1022-1024 Thieno[2,3-6]pyrazines, 4, 1023 electrophilic substitution, 4, 1024 Thieno[3,4-6]pyrazines, 4, 1024 Thieno[3,4-c]pyrazole, 4,6-dihydro-3-hydroxy-carbamates... 

Prior to the discovery of niacin receptors, medicinal chemistry efforts were mainly directed toward small heterocyclic carboxylic acids that are structurally similar to niacin. Systematic study of nitrogen-containing five- and six-membered heterocyclic carboxylic acids revealed that activity at GPR109A was significantly reduced for any of the variants of niacin shown in general structures (A and B) [45,46]. These heterocycles include pyrazole, isoxazole, thiazole, pyrazine, and pyrimidine. 

The presence of a 2-substitutent in 3-phenylazirines (17, R —H in Scheme 21) modifies the mode of reaction with molybdenum carbonyl.47 In contrast to pyrazine formation for (17, R =H see Section V,C,2), the alkenyl azirine (18, Scheme 22) is transformed in excellent yield into 2-phenyl-5-carboxy-methylpyrrole. This product probably arises by intramolecular cyclization within an intermediate dienylnitrene intermediate, and related reactions have been devised to synthesize isoxazoles (see Section IV,E,2) and pyrazoles (see Section IV,D,1).47 The molybdenum carbonyl-promoted formation of 2,5-disubstituted pyrroles47 has analogy in uncatalyzed thermal, but not photochemical decomposition of 3-phenyl-2//-azirine 2-acrylate.49... 

The ring cleavage of 3-aryl-2-substituted-2//-azirines by molybdenum hexacarbonyl has been described earlier in regard to the synthesis of pyrroles, pyrazoles and isoxazoles. In contrast to this behavior, analogous reactions of 2-unsubstituted derivatives lead to the formation of mixtures of 2,5-diarylpyrazines (139) and isomeric 3,6- and 1,6-dihydropyrazine derivatives (140,141) (Scheme 163).47,53 It is possible that the pyrazine products are formed by an intermolecular nitrene mechanism akin to the intramolecular processes described earlier (see Scheme 22 in Section IV,A,1). 

Recent literature examples involve the use of the Suzuki protocol for the highspeed decoration of various heterocyclic scaffolds of pharmacological or biological interest, including pyrimidines [45], pyridazines [46], pyrazines [47], chromanes [48], and pyrazoles [49] (Scheme 6.19). 

There are two distinct classes of compounds that fit the criteria mentioned above alkene-functionalized chalcone derivatives (Fig. IB) and enone-functionalized chalcone derivatives (Fig. 1C). Within each class, both aromatic and non-aromatic compounds exist. Those compounds functionalized at the alkene include i) 3-membered heterocycles, e.g., epoxide and aziri-dine compounds, ii) 5-membered aromatic derivatives including fused and non-fused compounds, and iii) 6-membered aromatic pyrazine compounds. The enone-functionalized compounds include i) 5-membered aromatics such as pyrazole and isoxazole compounds, ii) 5-membered non-aromatic compounds for example pyrazolines and isoxazolines, and iii) 6-membered non-aromatics where a discussion of heterocyclic and non-heterocyclic compounds will be given for completeness. 

Dihydropyrazolo[l,5-a]pyrazine-4,7-diones 205 were synthesized by Nikulnikov et al. using tcrt-butyl isocyanide 209 as a convertible isocyanide [62]. The Ugi reaction of tert-butyl isocyanide and pyrazole-3-carboxylic acids 208 with various aldehydes 206 and amines 207 yields tert-butyl amides 210, which undergo cycli-zation into glacial acetic acid under microwave irradiation (Scheme 37). 

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