(
400 MHz, DMSO-d ) δ 9.55 (s, 1H), 8.66 (dd, J = 11.9, 6.2 Hz, 2H), 7.93 – 7.85 (m, 2H), 7.62
6
(dd, J = 7.7, 4.8 Hz, 1H), 7.30 (t, J = 8.0 Hz, 1H), 6.88 (dd, J = 7.9, 2.5 Hz, 1H), 4.11 (t, J = 4.6
1
3
Hz, 4H), 3.85 (t, J = 4.7 Hz, 4H). C NMR (101 MHz, DMSO-d6): δ 162.7, 158.9, 158.0, 150.4,
1
48.9, 147.0, 139.5, 133.3, 132.2, 129.8, 121.3, 119.2, 117.6, 115.1, 115.0, 66.5, 45.8. HRMS (ESI)
+
calcd C H N O [M + H] 349.1300, found 349.1294.
1
9
17
4
3
3
-(4-Morpholinopyrido[3',2':4,5]furo[3,2-d]pyrimidin-2-yl)phenyltrifluoromethane
sulfonate (8): To the phenol 7 (174mg, 0.5 mmol) in anhydrous CH Cl was added pyridine (0.1ml,
2
2
1
mmol) and the solution was cooled to 0 °C. Trifluoromethanesulfonic anhydride (0.13ml, 0.6
mmol) was added dropwise and the mixture was warmed to r.t. The reaction was complete within
0 min. The reaction mixture was diluted with dichloromethane and washed successively with
1
saturated NaHCO and brine. After drying over MgSO4, the solution was concentrated and the
3
residue was purified by column chromatography on silica gel with hexane-ethyl acetate (4:1 to
1
2
:1) as eluent to give the triflates 8 (0.20 g, 84% yield) as pale yellow: H NMR (400 MHz, DMSO-
d6) δ 8.72 – 8.67 (m, 2H), 8.55 (dt, J = 7.8, 1.4 Hz, 1H), 8.39 (t, J = 2.0 Hz, 1H), 7.74 (t, J = 8.0
Hz, 1H), 7.67 – 7.62 (m, 2H), 4.13 (t, J = 4.7 Hz, 4H), 3.85 (t, J = 4.7 Hz, 4H).
4
-Morpholino-2-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrido[3',2':4,5]
furo[3,2-d]pyrimidine (PI-103BE, 9): A nitrogen-flushed 25 mL round-bottomed flask was
charged with PdCl (dppf) (8 mg, 0.01 mmol), KOAc (15 mg 0.15 mmol), bis(pinacolato)diboron
2
(34mg, 0.12 mmol), and the aryl triflate 8 (48mg, 0.1 mmol), then anhydrous dioxane (3 mL) was
added and the solution was stirred for 3 h at 80 °C. The reaction mixture was extracted with EtOAc,
the organic layer was washed with brine, and dried over anhydrous MgSO4. The organic solvent
was removed under reduced pressure and the crude was purified by column chromatography with
1
hexane-ethyl acetate (5:1 to 3:1) as eluent to afford the product 9 (36 mg, 76% yield): H NMR
(400 MHz, Chloroform-d) δ 8.89 (s, 1H), 8.62 (dd, J = 4.8, 1.5 Hz, 1H), 8.58 (d, J = 7.7 Hz, 1H),
7
1
.93 (d, J = 7.2 Hz, 1H), 7.56 – 7.45 (m, 3H), 4.26 (t, J = 4.7 Hz, 4H), 3.94 (t, J = 4.8 Hz, 4H),
1
.40 (s, 12H). H NMR (300 MHz, DMSO-d6): δ 8.76 (s, 1H), 8.73 (dd, J = 7.8, 1.8 Hz, 1H), 8.67
(dd, J = 5.1, 1.5 Hz, 1H), 8.53 (d, J = 8.1 Hz, 1H), 7.79 (d, J = 7.2 Hz, 1H), 7.61 (m, 1H), 7.53 (t,
1
3
J = 7.8 Hz, 1H), 4.11 (t, J = 4.7 Hz, 4H), 3.84 (t, J = 4.8 Hz, 4H), 1.34 (s, 12H). C NMR (75
MHz, DMSO-d6): 163.18, 159.34, 151.01, 149.54, 147.62, 138.16, 137.20, 134.65, 133.95, 133.05,