Potassium Carbonate → N-(4-fluorophenyl)-7-methoxy-6-(3-(tetrahydro-2H-[1,4]dioxino[2,3-c]pyrrol-6(3H)-yl) propoxy) quinazolin-4-amine

温度

70 °C

A mixture of hexahydro-2H-[1,4]dioxino[2,3-c]pyrrole (0.39 g, 3.0 mmol, 1.0 eq), N-(4-fluorophenyl)-6-(3-chloropropoxy)-7-methoxyquinazolin-4-amine (868 mg, 2.40 mmol, 0.80 eq), anhydrous K2CO3 (2.07 g, 15.0 mmol, 5.0 eq) and tetrabutylammonium iodide (55 mg, 0.15 mmol, 0.05 eq) in DMF (10 mL) was heated at 70° C. for 11 h. The reaction mixture was cooled to room temperature and quenched with water (10 mL). The resulted mixture was diluted with EtOAc (20 mL) and the organic phase was separated from the mixture. The water phase was extracted with EtOAc (20 mL×3). The combined organic phases were dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (20:1 (v/v) CH2Cl2/CH3OH) to give the crude product, which was recrystallized from CH2Cl2/PE to afford the title compound as a pale yellow solid (196 mg, 22.00%), HPLC:96.21%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 455.2 (M+1); 1H NMR (400 MHz, CDCl3) δ: 2.00 (2H, m), 2.63 (2H, m), 2.72 (2H, m), 2.90 (2H, dd, J=2.8, 6.1 Hz), 3.28 (1H, br s), 3.52 (2H, m), 3.76 (2H, m), 3.91 (3H, s), 4.05 (4H, d, J=4.4 Hz), 7.03 (1H, t, J=8.4 Hz), 7.18 (1H, s), 7.29 (1H, s), 7.63 (1H, dd, J=4.8, 8.4 Hz), 8.42 (1H, br s), 8.60 (1H, s) ppm.

1. temperatureThe reaction mixture was cooled to room temperature
2. customquenched with water (10 mL)
3. additionThe resulted mixture was diluted with EtOAc (20 mL)
4. customthe organic phase was separated from the mixture
5. extractionThe water phase was extracted with EtOAc (20 mL×3)
6. dry with materialThe combined organic phases were dried over anhydrous Na2SO4
7. concentrationconcentrated in vacuo
8. customThe residue was purified by a silica gel column chromatography (20:1 (v/v) CH2Cl2/CH3OH)
9. customto give the crude product, which
10. customwas recrystallized from CH2Cl2/PE

ORDレコード

ord-aed5479ae32947298372d89608e5565c

出典データセット

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09181277B2