Methods of synthesis and purification of heteroaryl compounds

A method of preparing a compound of formula (I),

• the method comprising contacting a compound of formula (III)
• with R1—Y in a solvent, in the presence of dichloro[1,1′-bis(ditert-butylphosphino)ferrocene]palladium or dichlorobis(p-dimethylamino phenylditbutylphosphine)palladium(II), wherein said contacting occurs under conditions suitable to provide a compound of formula (I), wherein:
• X is halogen, B(OR+)2 or Sn(R++)3;
• Y is halogen, triflate, B(OR+)2 or Sn(R++)3;
• wherein
• a) when X is halogen, then Y is B(OR+)2 or Sn(R++)3;
• or
• b) when Y is halogen or triflate, then X is B(OR+)2 or Sn(R++)3;
• wherein each R+ is independently hydrogen or substituted or unsubstituted C1-3 alkyl, or each R+, together with the boron atom and the atoms to which they are attached, form a cyclic boronate;
• and R++ is a C1-4 alkyl;
• and wherein
• R1 is substituted or unsubstituted C1-8 alkyl, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted heterocyclylalkyl;
• R2 is H, substituted or unsubstituted C1-8 alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heterocyclylalkyl, substituted or unsubstituted aralkyl, or substituted or unsubstituted cycloalkylalkyl;
• R3 and R4 are each independently H, substituted or unsubstituted C1-8 alkyl, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heterocyclylalkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted cycloalkylalkyl, or R3 and R4, together with the atom to which they are attached, form a substituted or unsubstituted cycloalkyl or substituted or unsubstituted heterocyclyl;
• or R2 and one of R3 and R4, together with the atoms to which they are attached, form a substituted or unsubstituted heterocyclyl;
• provided the compound is not 6-(4-hydroxyphenyl)-4-(3-methoxybenzyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one, 6-(4-(1H-1,2,4-triazol-5-yl)phenyl)-3-(cyclohexylmethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one, or (R)-6-(4-(1H-1,2,4-triazol-5-yl)phenyl)-3-(cyclohexylmethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one.