Vps

Uses

1-[[4''-(Cyclopropylmethyl)-2-(4-pyridinylamino)[4,5''-bipyrimidin]-2''-yl]amino]-2-methyl-2-propanol is a selective PI 3-kinase VPS34 inhibitor. VPS34 inhibitors can be used to investigate autophagy, a degradation process that recycles cellular components.

Synthesis

Synthesis of 1-((4'-(cyclopropylmethyl)-2-(pyridin-4-ylamino)-[4,5'-bipyridin]-2'-yl)amino)-2-methylpropan-2-ol (1 Ot): a new synthesis of 1-((4'-(cyclopropylmethyl)-2-(pyridin-4-ylamino)-[4,5'-bipyridin]-2'-yl)amino)-2-methylpropan-2-ol (1 Ot) was carried out by adding a new synthesizer to the (Z)-1-cyclopropyl-4-(dimethylamino)-3-(2-( pyridin-4-ylamino)pyrimidin-4-yl)but-3-en-2-one (9) (50 mg, 0.155 mmol) was added to a solution of 1-(2-hydroxy-2-methylpropyl)guanidine and potassium carbonate (107 mg, 0.773 mmol) in DMF (1288 μL). The reaction mixture was stirred at 120 °C for 2 hours. Upon completion of the reaction, the crude product was purified by reversed-phase HPLC (gradient: 30-90% organic phase, 15 min), followed by further purification using Biotage silica gel chromatography (10 g SNAP column, elution gradient: 100% DCM to 12% MeOH/DCM) to afford the target product (23.8 mg, 39% yield).

References

[1] Patent: WO2012/85815, 2012, A1. Location in patent: Page/Page column 65-66
[2] ACS Medicinal Chemistry Letters, 2016, vol. 7, # 1, p. 72 - 76