Triphenylphosphine → 3-chloro-5-[(4-methyl-2-oxo-1-{2-[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl]ethyl}-1,2-dihydropyridin-3-yl)oxy]benzonitrile

To a solution of 2-[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl]ethanol (14.6 mg, 0.059 mmol) in CH2Cl2 (400 ul) was added 3-chloro-5-[(4-methyl-2-oxo-1,2-dihydropyridin-3-yl)oxy]benzonitrile (15.4 mg, 0.059 mmol), and the resulting mixture was stirred over an ice bath for 5 minutes. The mixture was then treated with triphenylphosphine (30.9 mg, 0.118 mmol) and then diisopropylyazodicarboxylate (13 ul, 0.068 mmol) and stirred over an ice bath for 10 minutes and then at 25° C. for 30 minutes. LC-MS showed the reaction was not complete, and so the mixture was re-cooled over an ice bath and treated with additional diisopropylazodicarboxylate (10 μL, 0.052 mmol). This mixture was stirred over an ice bath for 5 minutes and then stirred at 25° C. for 20 minutes to give a 3:2 mixture of 0 to N alkylation. After this time, the reaction was quenched with MeOH (1 mL) and purified on Gilson LC using a Luna reverse phase column (10μ, C18, 250×21.2 mm) and eluting with a gradient of 5-95% ACN/water (0.5% TFA). The desired fractions were combined and evap in vacuo to give the title compound. LRMS (M+1): 489.9/405.9.

1. stirringstirred over an ice bath for 10 minutes
2. waitat 25° C. for 30 minutes
3. temperatureso the mixture was re-cooled over an ice bath
4. stirringThis mixture was stirred over an ice bath for 5 minutes
5. stirringstirred at 25° C. for 20 minutes
6. customto give
7. additiona 3:2 mixture of 0 to N alkylation
8. customAfter this time, the reaction was quenched with MeOH (1 mL)
9. custompurified on Gilson LC
10. washeluting with a gradient of 5-95% ACN/water (0.5% TFA)

ORD 기록

ord-aa111ba88bb34aab8f416d49920c774f

출처 데이터셋

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08404856B2