4-ethynyloxan-4-ol

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Using Method C above, 4-Ethynyl-tetrahydro-pyran-4-ol (0.16 g, 1.26 mmol) (Example 85A) was coupled with (Z)-3-[(4-acetyl-1H-pyrrol-2-yl)methylene]-1,3-dihydro-5-fluoro-4-iodo-2H-indol-2-one (0.2 g, 0.50 mmol) (Example 90B above) using (Ph3P)4Pd (58.4 mg) and CuI (9.6 mg) as catalyst in DMF (15 mL) and Et3N (15 mL) as solvent at 85° C. for 18 h. (Yield 102 mg, 52%).

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Using Method C above, 4-ethynyl-tetrahydro-pyran-4-ol (41.1 mg, 0.33 mmol) (Example 85A) was coupled with (Z)-1,3-dihydro-5-fluoro-4-iodo-3-[(3-methoxy-1H-pyrrol-2-yl)methylene]-2H-indol-2-one (50 mg, 0.13 mmol) (Starting Material 6) using (Ph3P)4Pd (15 mg) and CuI (2.5 mg) as catalyst in DMF (4 mL) and Et3N (4 mL) as solvent at 85° C. for 7 h to yield (Z)-1,3-Dihydro-5-fluoro-4-[(4-hydroxy-tetrahydro-pyran-4-yl)ethynyl]-3-[(3-methoxy-1H-pyrrol-2-yl)methylene]-2H-indol-2-one. (Yield 36 mg, 75%).

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of ethynylmagnesium chloride in THF (0.5 M, 120 mL, 60 mmol) was added with cooling in an ice-water bath to a solution of tetrahydro-4H-pyran-4-one (4.96 g, 50 mmol) (Aldrich) in diethyl ether (300 mL) dropwise over 15 min. The mixture was stirred with cooling for 3 h. Aqueous ammonium chloride solution (100 mL, 15% W/V) was then added and mixture extracted with ether (2×200 mL). The ether layers were washed with saturated aqueous sodium chloride solution (200 mL), then combined, dried (MgSO4), filtered and concentrated to give 4-Ethynyl-tetrahydro-pyran-4-ol as a colorless oil that solidified on standing. (Yield 6.01 g, 96.2%). with cooling for 3 h mixture extracted with ether (2×200 mL) The ether layers were washed with saturated aqueous sodium chloride solution (200 mL) dried (MgSO4) filtered concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Using Method C above, 4-Ethynyl-tetrahydro-pyran-4-ol (0.16 g, 1.26 mmol) (Example 85A) was coupled with (Z)-3-[(4-acetyl-1H-pyrrol-2-yl)methylene]-1,3-dihydro-5-fluoro-4-iodo-2H-indol-2-one (0.2 g, 0.50 mmol) (Example 90B above) using (Ph3P)4Pd (58.4 mg) and Cul (9.6 mg) as catalyst in DMF (15 mL) and Et3N (15 mL) as solvent at 85° C. for 18 h. (Yield 102 mg, 52%).