Potassium Phosphate, Tribasic → 2-chloro-5-((R)-1-(4-chlorophenyl)ethyl)-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one

温度

105 °C

To an oven dried vial were added 4-(5-bromo-2-chloropyrimidin-4-yl)-N—((R)-1-(4-chlorophenyl)ethyl)morpholine-3-carboxamide (PREPARATION x31, 574 mg, 1.247 mmol), Xantphos (54.1 mg, 0.094 mmol), potassium phosphate tribasic (265 mg, 1.247 mmol) and palladium(II)acetate (14.00 mg, 0.062 mmol) in dioxane (5 mL) and tert-butanol (1 mL). The reaction mixture was degassed for 5 minutes with N2. The vial was then sealed and heated to 105° C. and the contents were stirred for 72 hours to give a brown suspension. The reaction mixture was subsequently diluted with ethyl acetate and washed with aqueous saturated NH4Cl (3×5 mL) and brine (3×5 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo to give a crude product which was loaded onto an ISCO® silica gel cartridge (40 g) and eluted using an ethyl acetate/hexane gradient. The product was collected and concentrated in vacuo to afford the title compound as a white solid (58 mg, 12%). 1H NMR (400 MHz, DMSO-d6) δ 1.68-1.80 (m, 3H), 2.91-3.02 (m, 1H), 3.46-3.64 (m, 1H), 3.64-3.76 (m, 1H), 3.88-4.01 (m, 1H), 4.13-4.27 (m, 2H), 4.41-4.60 (m, 1H), 5.99-6.24 (m, 1H), 7.27-7.49 (m, 4H), 7.50-7.57 (m, 1H). ESI-MS m/z [M+H]+ calc'd for C17H16Cl2N4O2, 379.07. found 379.3.

1. customTo an oven dried vial
2. customThe reaction mixture was degassed for 5 minutes with N2
3. customThe vial was then sealed
4. customto give a brown suspension
5. washwashed with aqueous saturated NH4Cl (3×5 mL) and brine (3×5 mL)
6. dry with materialThe combined organic layers were dried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customto give a crude product which
10. washeluted
11. customThe product was collected
12. concentrationconcentrated in vacuo

ORDレコード

ord-2b929ca664384459991ca54a1216acd8

出典データセット

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08791107B2