2-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenyl → [4-(3-{6-[(Thiophen-2-ylmethyl)-amino]-pyridin-2-yl}-imidazo[1,2-a]pyrazin-8-ylamino)-cyclohexyl]-carbamic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

A mixture of {4-[3-(6-bromo-pyridin-2-yl)-imidazo[1,2-a]pyrazin-8-ylamino]-cyclohexyl}-carbamic acid tert-butyl ester (from Example 40 supra) (0.244 g, 0.5 mmol), thiophen-2-yl-methylamine (0.113 g, 1.0 mmol), Pd2(dba)3 (30 mg), Davephos (40 mg), NaOtBu (100 mg, 0.1 mmol) in dioxane (15 mL) in a sealed tube was bubbled with N2 for several minutes and then heated under N2 at 110° C. for 16 hour. The solution was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure. The residue was purified first by chromatography (CH2Cl2:MeOH, 100:1), then by preparative-HPLC to give [4-(3-{6-[(thiophen-2-ylmethyl)-amino]-pyridin-2-yl}-imidazo[1,2-a]pyrazin-8-ylamino)-cyclohexyl]-carbamic acid tert-butyl ester. (Yield 100 mg, 38%). LC-MS: [M+H]+ 520.

Provenance & Evidence