2.3.5- Trifluoro-6- pyrazine

Another important acid-induced process in fluorinated diazine chemistry is fluorine-halogen exchange promoted by Lewis acids. In some cases the switching of regiochemistry also observed. Thus in a case of dimethyl-(3,5,6-trifluoro-pyrazin-2-yl)-amine 300 treatment with AICI3 leads to exchange of flnorine at 6-th position unlike with MeaNH substitution (compare with Fig. 14). Subsequently dialkylamino - AICI3 treatment leads to dichloropyrazine 303, which unavailable by selective manner from tetrachloropyrazine (Scheme 45) [164]. 

Perfluoropyrazine (17) on reaction with sodium methoxide gives 2,3,5-trifluoro-6-methoxy-pyrazine and 2,3-difluoro-5,6-dimethoxypyrazine.130... 

The treatment of 4-arylperhydropyrido[2,l-c][l,4]oxazin-6-ones (07USA2007/Oil7839, 08WOP2008/013213) and 6-oxo-4-(3,4,5-trifluoro-phenyl)perhydropyrido[l,2-a]pyrazine-2-carboxylate (07USA2007/ 0117839) with Me3SiI and A NdV N -tetramethylethylenediamine in CH2CI2 in a N2 atmosphere at 0 °C followed by the addition of I2 and stirring at 0 °C for another 30 min yielded 7-iodo derivatives. 

Pyrazinetetracarboxylic acid is converted into tetra(trifluoro-methyl)pyrazine by the action of sulfur tetrafluoride [Eq. (13)].244... 

Amino-5-bromo-3-carbamoylpyrazine heated with trifluoroacetamide and sodium ethoxide (or butoxide) gave 6-ethoxy(or butoxy)-4-hydroxy-2-trifluoro-methylpteridine (49) (987) and 2-chloro-3-pyridiniopyrazine chloride with methoxide ion gave 2,3-dimethoxypyrazine (765). 2-Amino-3-bromo-5-phenyl-pyrazine with sodium methoxide in methanol at 134° for 8 hours formed 2-amino-3-methoxy-5-phenylpyrazine (365a) and 3-bromo-2-hydroxy-5-phenylpyrazine similarly treated gave 2-hydroxy-3-methoxy-5-phenylpyrazine (365a). 

Pyrazines with three and four halogeno substituents may react readily with alkoxide ions to give mono- and dialkoxypyrazines depending on the reaction conditions. The following pyrazines have been prepared accordingly 2,5-difluoro-3-methoxy and 5-fluoro-2,3-dimethoxy (an excess of sodium methoxide) (885) 2,5-difluoro-3-methoxy-6-methyl (at —40°) (851) and 2-fluoro-5,6-dimethoxy-3-methyl (at +20°) (851) 2,3,5-trifluoro-6-methoxy (at — 10°) (851) and 2,3-difluoro-5,6-dimethoxy (at 20°) (851) (compare orientation with that given in reference 852) 2-ethoxy-3,5,6-trifluoro (at — 10°) (851) 2-f-butoxy-3,5,6-trifluoro (at —20°) (851) 2,3,5-trifluoro-6-(2 -hydroxyethoxy) (851) and 23-4ifluoro-5,6-... 

Alkylations of halogenopyrazines have been effected as follows tetrafluoro-pyrazine with ethereal methyllithium at — 70° gave 2,3,5-trifluoro-6-methylpyrazine (851, 965), and with butyllithium in ether-hexane gave 2-butyl-3,5,6-trifluoro-, 2,5-dibutyl-3,6-difluoro-, and 2,3,5-tributyl-6-fluoropyrazines (851) tetrachloro-... 

Methoxypyrazines (31) have been prepared by diazomethane methylation of 2-hydroxy-3-isobutylpyrazine (60, 311, 367), 2-hydroxy-3-isopropylpyrazine (59, 367), 2-hydroxy-3-propyl(ethyl or hexyl)pyrazine (367), 3-hydroxy-2-isobutyl-5(and 6)methylpyrazine and 2-hydroxy-3-isobutyl-5,6-dimethylpyrazine (368), 2,3-dihydroxypyrazine (832), 2-hydroxy-5-methoxy- and 2,5-dihydroxy-3,6-diphenyl-pyrazine (832), 2-hydroxy-6-methoxy(and benzyloxy)pyrazine (832), 2,6-dihydroxy-3,5-diphenylpyrazine (873), 2,3,5-trifluoro-6-hydroxypyrazine (851), 2-chloro-6-hydroxy-3,5-diphenylpyrazine (873), 2-chloro-6-hydroxy-5-methyl-3-phenylpyrazine (873), 2-chloro-6-hydroxy-3-methyl-5-phenylpyrazine (873), 5,6-dichloro-1 -cyclohexyl-34iydroxy-2-oxo-l, 2-dihydropyrazine (853), 2-chloro-5-hydroxy-3-methoxy-6-methoxycarbonylpyrazine (881), 2-(4 -amino-3, 5 -dibromo-phenylsulfonamido)-3Tiydroxy-6-methoxypyrazine (881), 2-amino-3-hydroxy-... 

Sitagliptin phosphate monohydrate (1, 7-[(3i )-3-amino-l-oxo-4-(2,4,5-trifluoro-phenyl)butyl]-5,6,7,8-tetrahydro-3-(trifluoromethyl)-l,2,4-triazolo[4,3-a]pyrazine phosphate monohydrate, Januvia ) is an oral hypoglycaemic drug, an inhibitor of the dipeptidyl peptidase-IV (DPP4) enzyme. It is widely used in the therapy of type 2 diabetes mellitus [1,2]. 

Ci2Hi2Fi80i8Pr2f Tetrakis-M-trifluoroacetato-bis(triaquo(trifluoro-acetato)praseodymium(IlI)), 44B, 870 Ci2Hi6Cr2N208, Tetrakis(M-acetato)(pyrazine)dichromium(Cr-Cr), 46B, 1022... 

Kim D, Wang L, Beconi M, Eirmann GJ, Fisher MH, He H, Hickey GJ, Kowalchick JE, Leiting B, Lyons K, Marsilio E, McCann ME, Patel RA, Petrov A, Scapin G, Patel SB, Roy RS, Wu JK, Wyvratt MJ, Zhang BB, Zhu L, Thornherry NA, Weber AE. (2R)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro [l,2,4]triazolo[4,3-a]pyrazin-7(8/0-yl]-l-(2,4,5-trifluoro-phenyl)butan-2-amine a potent, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. J. Med. Chem. 2005 48 141-151. 

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