Cesium carbonate → N1-(3-Fluoro-4-(thieno[2,3-d]pyrimidin-4-yloxy)phenyl)-N3-(4-fluorophenyl)malonamide

온도

120 °C

N1-(3-Fluoro-4-hydroxyphenyl)-N3-(4-fluorophenyl)malonamide (46 mg, 0.15 mmol, Compound B of Example 25), 4-chlorothieno[2,3-d]pyrimidine (17 mg, 0.10 mmol), cesium carbonate (49 mg, 0.15 mmol), and copper(I) chloride (10 mg, 0.10 mmol) were placed in a test tube. The tube was sealed, flushed with nitrogen, charged with 1-methyl-2-pyrrolidinone (0.3 mL) followed by 2,2,6,6-tetramethyl-3,5-heptanedione (4.0 μL, 0.02 mmol). The reaction was stirred at 120° C. for 1 h. The reaction mixture was purified by preparative HPLC. The appropriate fraction was concentrated to remove methanol and the resulting aqueous solution was made basic with saturated NaHCO3 solution (5 mL). The aqueous solution was extracted with EtOAc (3×10 mL) and the combined organic extracts were dried over anhydrous Na2SO4 and concentrated in vacuo to give the desired product as a colorless oil. Lyophilization with methanol/water gave the title compound (27 mg, 61%) as a white solid. 1H NMR (DMSO-d6) δ 10.7 (s, 1H), 10.4 (s, 1H), 8.77 (s, 1H), 8.15 (d, 1H, J=5.9 Hz), 7.95 (dd, 1H, J=12.8, 2.0 Hz), 7.85 (d, 1H, J=5.9 Hz), 7.77 (m, 2H), 7.54 (m, 2H), 7.30 (t, 2H, J=8.8 Hz), 3.48 (s, 2H); MS(ESI+) m/z 441.1 (M+H)+.

1. customThe tube was sealed
2. customflushed with nitrogen
3. additioncharged with 1-methyl-2-pyrrolidinone (0.3 mL)
4. customThe reaction mixture was purified by preparative HPLC
5. concentrationThe appropriate fraction was concentrated
6. customto remove methanol
7. extractionThe aqueous solution was extracted with EtOAc (3×10 mL)
8. dry with materialthe combined organic extracts were dried over anhydrous Na2SO4
9. concentrationconcentrated in vacuo

ORD 기록

ord-430d42a8c044495a825ed060124b1c7e

출처 데이터셋

uspto-grants-2007_02

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07173031B2