反应详情

温度

100 °C

To a solution of 6-chloro-4-(5-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3-oxazol-2-yl)-1-(phenylsulfonyl)-1H-indazole (50 mg, 0.103 mmol) in 1,4-dioxane (1.5 ml) and water (0.15 ml) was added {1-[1,1-dimethylethyl)(dimethyl)silyl]1-Hindol-4-yl}boronic acid (37 mg, 0.133 mmol), chloro[Z-(dimethylamino)-2-biphenylyl]palladium-(1R,4S)-bicyclo[2.2.1]hept-2-yl[(1S,4R)-bicyclo[2.2.1]hept-2-yl]phosphane (5.75 mg, 10.27 μmol) and potassium phosphate tribasic (65 mg, 0.308 mmol). The reaction mixture was heated under microwave irradiation at 100° C. for 40 min. The solvent was removed and the residue dissolved in 10% methanol in dichloromethane (2 ml) and purified by silica gel chromatography, eluting with a gradient of cyclohexane and ethyl acetate. The appropriate fractions were concentrated to give a brown gum which was treated directly with tetra-n-butylammonium fluoride (0.2 ml, 0.2 mmol, 1M in tetrahydrofuran) and allowed to stand at 20° C. for 18 h. The solvent was removed and the residue dissolved in 1,4-dioxane (1 ml) and treated with 2M sodium hydroxide (1 ml) and allowed to stand at 20° C. for 48 h. The solvent was removed and the residue triturated with 10% methanol in dichloromethane then purified by silica gel chromatography, eluting with a gradient of dichloromethane and methanol to give a pale brown solid which was further purified by SCX SPE (1 g), eluting with 0.5M ammonia in 1,4-dioxane. The solvent was removed and the residue further purified by MDAP to give the title compound as a white solid (14 mg).

1. customThe solvent was removed
2. dissolutionthe residue dissolved in 10% methanol in dichloromethane (2 ml)
3. custompurified by silica gel chromatography
4. washeluting with a gradient of cyclohexane and ethyl acetate
5. concentrationThe appropriate fractions were concentrated
6. customto give a brown gum which
7. customThe solvent was removed
8. dissolutionthe residue dissolved in 1,4-dioxane (1 ml)
9. additiontreated with 2M sodium hydroxide (1 ml)
10. waitto stand at 20° C. for 48 h
11. customThe solvent was removed
12. customthe residue triturated with 10% methanol in dichloromethane
13. customthen purified by silica gel chromatography
14. washeluting with a gradient of dichloromethane and methanol
15. customto give a pale brown solid which
16. customwas further purified by SCX SPE (1 g)
17. washeluting with 0.5M ammonia in 1,4-dioxane
18. customThe solvent was removed
19. customthe residue further purified by MDAP