Hydrochloric Acid → HCID 178432266, compound

Participants

Reaction Conditions

Reaction Steps

[4-(2-Amino-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)-phenyl]-morpholin-4-yl-methanone (see “C41”, 5-bromo-2-methyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazole (1.1 eq.), chloro[2-(dicyclohexylphosphino)-3,6-dimethoxy-2′-4′-6′-tri-i-propyl-1,1′-biphenyl]2-(2-aminoethyl)phenyl)Pd(II) (0.03 eq), 2-(dicyclohexylphosphino)-3,6-dimethoxy-2′-4′-6′-tri-i-propyl-1,1′-biphenyl (0.03 eq) are dissolved in dry t-butanol under nitrogene, before lithium bis(trimethylsilyl)amide, (3 eq., 20% (ca 1.06M) solution in THF/ethylbenzene) is added. The resulting mixture is heated to 110° C. for 1 h. Work-up as described in general procedure 3 gives the SEM-protected intermediate. (4-{2-[2-Methyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-5-ylamino]-[1,2,4]triazolo[1,5-a]pyrazin-8-yl}-phenyl)-morpholin-4-yl-methanone is dissolved in ethanol. Concentrated HCl is added and the reaction mixture is heated to 65° C. for 4 h and monitored by LCMS. Upon completion, the mixture is neutralized with saturated NaHCO3-solution and the layers are separated, the aqueous phase is 3 times extracted with DCM. The combined organic phases are dried with Na2SO4 and concentrated. Purification gives the title compound as a solid.

Provenance & Evidence