Hydrochloric Acid → HCID 178463357, compound

Temperature

100 °C

A solution of 5-chloro-N-(6-methoxypyridin-3-yl)-3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-amine (0.200 g, 0.443 mmol) and ethylamine (0.553 mL, 1.106 mmol) (Aldrich, St. Louis, Mo.) in THF (10 mL) was treated with sodium tert-butoxide (0.128 g, 1.328 mmol) and 2-di-t-butylphosphino-2′,4′,6′-tri-isopropyl-1,1′-biphenyl (0.030 g). The mixture was deoxygenated and treated with Pd2(dba)3 (0.041 g, 0.044 mmol) under N2. The flask was fitted with a reflux condenser, then placed into a pre-heated bath at 80° C. and stirred overnight. The reaction mixture was diluted with saturated aqueous NaHCO3 (10 mL) and extracted with CH2Cl2 (2×25 mL). The combined organic extracts were washed with NaHCO3 (20 mL) and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give a tan oil. A glass microwave reaction vessel was charged with the crude oil and 1 N aqueous HCl (1.5 mL) in THF (3 mL). The reaction mixture was stirred and heated in a Discover model microwave reactor (CEM, Matthews, N.C.) at 100° C. for 8 min (100 watts, Powermax feature on). The mixture was concentrated and neutralized with SiliCycle Si-Carbonate Silica Gel (SiliCycle Inc., Quebec City, Canada) (0.800 g). The mixture was diluted with THF (5 mL) and allowed to stir under inert atmosphere overnight. The mixture was concentrated, diluted with DCM (10 mL) and filtered. The desired product was released from the silica by rinsing with methanol (20 mL). The filtrate was concentrated and triturated with diethyl ether to give N5-ethyl-N2-(6-methoxypyridin-3-yl)-3-(2-methyl-9H-purin-6-yl)pyridine-2,5-diamine (0.065 g, 0.173 mmol, 39.0% yield) as a tan solid. MS (ESI pos. ion) m/z 377 (M+H)+. 1H NMR (400 MHz, CD3OD) δ 8.65 (d, 1H); 8.35 (d, 1H); 8.20 (s, 1H); 7.92 (d, 1H); 7.76 (s, 1H); 6.75 (d, 1H); 3.87 (s, 3H); 3.20 (m, 2H); 2.80 (s, 3H); 1.29 (s, 3H).

1. customThe mixture was deoxygenated
2. customThe flask was fitted with a reflux condenser
3. customplaced into a pre-heated bath at 80° C.
4. extractionextracted with CH2Cl2 (2×25 mL)
5. washThe combined organic extracts were washed with NaHCO3 (20 mL)
6. dry with materialdried over Na2SO4
7. filtrationThe solution was filtered
8. concentrationconcentrated in vacuo
9. customto give a tan oil
10. customA glass microwave reaction vessel
11. stirringThe reaction mixture was stirred
12. concentrationThe mixture was concentrated
13. additionThe mixture was diluted with THF (5 mL)
14. stirringto stir under inert atmosphere overnight
15. concentrationThe mixture was concentrated
16. additiondiluted with DCM (10 mL)
17. filtrationfiltered
18. washby rinsing with methanol (20 mL)
19. concentrationThe filtrate was concentrated
20. customtriturated with diethyl ether

ORD record

ord-87352264d7784c37ab85e9ea1e0d19b3

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08772480B2