반응 #359218

반응 방정식

3-(2-Methoxy-phenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridine

2-Bromo-thiazole-5-carboxylic acid methyl ester

acetonitrile

Na2CO3

→

title compound

수율 81.0%

2-[3-(2-Methoxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-thiazole-5-carboxylic acid

수율 81.0%

용매

Et2O

반응 조건

후처리

1. 1
   기타Into a 20 mL Personal Chemistry microwave reaction
2. 2
   기타The vial was sealed
3. 3
   기타purged with N2
4. 4
   기타irradiated in a Personal Chemistry Optimizer at 130° C. for 30 min
5. 5
   workup.ADDITIONThe reaction mixture was diluted with EtOAc
6. 6
   기타The layers were separated
7. 7
   추출the aqueous phase was extracted 5× with EtOAc
8. 8
   workup.ADDITIONThe combined organic phase was treated with brine
9. 9
   건조dried (Na2SO4)
10. 10
    여과filtered
11. 11
    농축concentrated
12. 12
    workup.DISSOLUTIONThe crude product was dissolved in 10 mL of a solution
13. 13
    농축The reaction mixture was concentrated under vacuum
14. 14
    기타The quenched reaction mixture
15. 15
    기타was partitioned between EtOAc and water
16. 16
    기타the layers were separated
17. 17
    추출the aqueous phase was extracted 2× with EtOAc
18. 18
    추출extracted 5× with EtOAc
19. 19
    workup.ADDITIONThe combined organic extracts was treated with brine
20. 20
    건조dried (Na2SO4)
21. 21
    여과filtered
22. 22
    농축concentrated

실험 절차

Into a 20 mL Personal Chemistry microwave reaction vial were added 3-(2-Methoxy-phenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridine (0.4992 g, 1.038 mmol), 2-Bromo-thiazole-5-carboxylic acid methyl ester (0.2592 g, 1.167 mmol), 1,1′-bis(diphenylphosphino)ferrocenepalladium(II)-dichloride dichloromethane adduct (95.4 mg, 0.117 mmol), acetonitrile (5 mL) and 2M aqueous Na2CO3 (5 mL). The vial was sealed, purged with N2, and irradiated in a Personal Chemistry Optimizer at 130° C. for 30 min. The reaction mixture was diluted with EtOAc and acidified with acetic acid to pH 5. The layers were separated, and the aqueous phase was extracted 5× with EtOAc. The combined organic phase was treated with brine, dried (Na2SO4), filtered and concentrated. The crude product was dissolved in 10 mL of a solution consisting of 1 part HClO4 (70%, ACS) and 20 parts glacial acetic acid, and the solution was stirred at rt for 4 h. The reaction mixture was concentrated under vacuum, and neutralized to pH 7 with saturated NaHCO3 followed by solid NaHCO3. The quenched reaction mixture was partitioned between EtOAc and water, the layers were separated, and the aqueous phase was extracted 2× with EtOAc. The aqueous phase was then acidified to pH 4 with acetic acid and extracted 5× with EtOAc. The combined organic extracts was treated with brine, dried (Na2SO4), filtered and concentrated. Trituration with Et2O afforded the title compound as a greenish-brown powder (0.296 g, 81% yield). 1H-NMR (500 MHz, d6-DMSO) δ 13.73 (br. s, 1H), 9.16 (s, 1H), 8.71 (s, 1H), 8.40 (s, 1H), 7.68 (d, J=8.0 Hz, 1H), 7.48 (t, J=8.0 Hz, 2H), 7.24 (d, J=8.0 Hz, 1H), 7.10 (t, J=7.5 Hz 1H), 3.87 (s, 3H); MS: m/z 353.1 [MH+].

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