2- pyrazine, formylation

Reduction of a 7-(2-oxoethyl) derivative with NaBH4 in EtOH at room temperature gave 7-(2-hydroxyethyl)-2-(2-pyrimidinyl)perhydropyrido[l, 2-u]pyrazine (99MIP6). Reduction of 7-formyl-8-[(4-cyanophenyl)methoxy]-1,3,4,6,11,1 lu-hexahydro-2//-pyrazino[l,2-A]isoquinoline-l,4-dione with NaBH4 yielded a 7-hydroxymethyl derivative (98MIP7). 

Hydroxy group of rru -7,9u-H-7-(prepared from 7-formyl-2-(2-pyrimidyl)perhydropyrido[l,2-u]pyrazine by the treatment with MeOCH2P(Ph)3Cl in the presence of -Pr2NH in THF at 0°C, than with BuLi at room temperature (99MIP6). 

Bei der Reduktion von 2-ChlorcarbonyI-pyrazin werden neben 20°/0 d.Th. 2-Formyl-pyrazin bereits 55% d.Th. 2-[Pyrazyl-(2)-methoxycarbonyl -pyrazin gebildet1 ... 

The 7-(2-oxoethyl) derivative was prepared from 7-formyl-2-(2-pyrimidyl)perhydropyrido[l,2- ]pyrazine by the treatment with MeOCHzP(Ph)3Cl in the presence of Pr 2NH in THF at 0°C, then with BuLi at room temperature < 1999WO99/020622>. Reaction of a 7-mesyloxymethyl group in perhydropyrido[l,2-tf Ipyrazine with NaCN in DMF at 110°C gave a 7-cyanomethyl derivative, which was converted into a 2-oxoethyl group by treatment first with DIBAL-H, then with 2M HC1. The 2-oxoethyl group was reacted with 4-FC6H4MgBr in THF at — 10°C to yield a... 

The (Z)- and ( )-styrylpyrazine structures 20j and 20k were assigned on the base of the mass, NMR, and UV spectral data. The mass spectrum of Z isomer (20j) shows a base peak (the molecular ion) at m/z 210 with a peak at m/z 133 formed by the loss of a phenyl group firom 20j. The H-NMR spectrum shows the presence of five aromatic and two olefinic protons in addition to one heteroaromatic proton and two methyl groups attached to the heteroaromatic nucleus. Ozonolysis of the Z isomer (20j) yields 3-formyl-2,5-dimethylpyrazine (487) and benzaldehyde, confirming the styryl moiety in 20j. The ( )-styryl derivative (20k) is readily isomerized to the Z isomer (20j) on exposure to sunlight (Scheme 60). Extraction of the pyrazines from I. humillis in the dark indicates that E isomer 20k is the naturally occurring product 144,145). 

Oxidation of 3-hydroxymethyl-2,3-dihydro-5H-pyrido[l,2,3-cfe][1,4] benzoxazin-5-ones with o-iodoxybenzoic acid in DMSO and with Dess-Martin periodinate in CH2CI2 afforded 3-formyl derivatives (08WOP2008/ 120003). Dehydrogenation of ethyl 10-[2-(ferf-butoxycarbonyl)-l,2,3,4,6,8a-hexahydropyrrolo[l,2-a]pyrazin-7-yl]-9-fluoro-3(S)-methyl-7-oxo-2,3-dihydro-7H-pyrido[l,2,3-de][l,4]oxazine-6-carboxylates in the presence of Pd/C with air in MeOH afforded 10-[2-(ferf-butoxycarbonyl)-l, 2,3,4-tetrahydropyrrolo[l,2-a]pyrazin-7-yl] derivatives, which then were deprotected (09BML4933). 

N-Heterocycles Pyridine Pyrazines Unsubstituted, 2,3-Dimethyl, MARM ++ 2,5-Dimethyl-3-ethyl, Methyl, 2-Ethyl-6-methyl, 2,5-Dimethyl, 2-Ethyl-5-methyl, 2,6-Dimethyl, Acetylmethyl, 2-(2-Furyl), Ethyl, 2-Methyl-5-(methylethyl), Trimethyl Pyrroles 2-Acetyl, N-Methyl-2-furyl, 1-Formyl, 1-Furfury 1-2-formyl, 5-Methvl-2-formvl Trimethylpyrazine (TMPy) (RV = 0.989)... 

The greater stability of the pyrazine ring to oxidation compared with that of benzene enables pyrazinecarboxylic acids to be prepared by permanganate oxidation of either quinoxalines or phenazines. The pyrazine ring is more stable than the pyrimidine ring to acid and alkaline hydrolysis. Thus, pteridine is converted into 2-amino-3-formylpyrazine on treatment with dilute sulfuric acid and N-(3-formyl-2-pyrazinyl)formamidine oxime on treatment with sodium carbonate and hydroxylamine (Scheme 11).136 Aminopyrazines and... 

Pyrazinecarbaldehydes can of course be recovered from their derivatives for example, the acetal, methyl 6-amino-5-cyano-3-diethoxymethyl- (249), gave methyl 6-amino-5-cyano-3-formyl-2-pyrazinecarboxylate (250) in 85% yield by selective hydrolysis in dilute hydrochloric acid at 20°C during 12 h 773 likewise, the extranu-clear acetal, 2-(3,3-diethoxypropyl)-3-ethoxycarbonylmethylpyrazine, gave 2-ethoxycarbonylmethyl-3-(2-formylethyl)pyrazine in 92% yield on hydrolysis in aqueous alcoholic hydrochloric acid at 35°C during 2 h.1249... 

Ethylaminoethyl)pyrazine Ethyl 3-amino-6-formyl-2-pyrazinecarboxylate... 

Prnpan 2-Dimethylamino-2-(4-nitro-phenyl)- El9a, 499 (Cl -> NR2) Pyrazin-l-oxid, 3,5(or3,6)-Diisopro-pyl-2-formyl- E9b/2, 322 (H -> CHO)... 

During the isolation of cathinone, 3,6-dimethyl-2,5-diphenyl pyrazine (3) was also found (14). This is doubtless an artifact, the product of oxidative dimerization of cathinone which involves the formation of condensation product 4 as an intermediate (18). Also found was the diketone (5) and the cinnamoyl compound (6) (14), later shown to have the (S) stereochemistry illustrated and named merucathinone (6,19,20). Merucathine (7) has also been isolated (6,21,22), and this and merucathinone are minor components. (-)-Norephedrine (8) also occurs in khat (14), and its iV-formyl derivative (9) has been found in plant material of South Arabian origin (23). Despite earlier positive reports, ephedrine and pseudoephedrine have not been verified as components of khat (14). HPLC has been employed to separate and quantify mixtures of the khatamines cathinone, (+)-norpseudoephedrine, and (—)-norephedrine in connection with a study of their distribution in different parts of the khat plant and in specimens of different geographical origin (20,21). 

A 2-amino-5-substituted-pyrazine refluxed with p-toluenethiol, 2-methoxy-ethanol, and 2-amino-6-formyl-4-hydroxypteridine followed by heating with acetic anhydride gave the 2-amino-4-hydroxy-6-[A -(5 -substituted-pyrazin-2 -yl)-acetamidomethyl]pteridine (34) (1244). 2-Amino-5-phenylpyrazine with isobutyral-dehyde in ether at room temperature gave 2-(3-isopropyl-6, 6-dimethyl-5, 6-dihydro-l, 2, 4 -trioxin-5 -yl)aniino-5-phenylpyrazine (35) (1245). 

Reduction of 2-methoxycarbonylpyrazine in tetrahydrofuran with lithium aluminum hydride at about — 70° gave 2-formylpyrazine (46%), but reduction of 2-chlorocarbonylpyrazine with lithium tri-r-butoxyaluminohydride in tetrahydrofuran gave 2-(pyrazin-2-ylmethoxycarbonyl)pyrazine (55%) and 2-formylpyrazine (20%) (1077), and 2-ethoxycarbonyl-3-methylpyrazine was reduced with lithium aluminum hydride in tetrahydrofuran at — 70° to 2-formyl-3-methylpyrazine (1185). 

Dehydrogenations of piperazines to pyrazines have been described in Section II.6, and the conversion of piperazine over catalysts (e.g., CuO) to give mostly pyrazine (90-94%) has been studied (1718). The oxidation of 1,4-diphenylpiperazine with manganese dioxide in chloroform at 20° to yield A, A -diformyl-A(, -diphenyl-ethylenediamine has been reported (1719). Formylpiperazines have been reported as formylating agents. Thiophene, 1,4-diformylpiperazine, and phosphoryl chloride are reported to give 2-formylthiophene (1720). 

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