反应详情

温度

70 °C

The product of Step 1 (175 mg, 0.326 mmol), palladium (II) acetate (7.32 mg, 0.033 mmol), and 1,3-bis(diphenylphosphino)propane (13.46 mg, 0.033 mmol) were combined in a 5 ml microwave vial, sealed, and taken up in DMF (3 ml)/MeOH (1.5 ml). CO was bubbled through the reaction mixture for 5 min. Triethylamine (0.091 ml, 0.653 mmol) was added, a CO balloon was attached, and the reaction was stirred at 70° C. overnight. The reaction was diluted with saturated NH4Cl solution and extracted with EtOAc (2×). The combined organic layers were washed with brine, dried (MgSO4), and evaporated. The crude material was purified by chromatography on silica gel (Biotage 25 g SNAP, 50-100% EtOAc/hexanes, 50-100% EtOAc/toluene) followed by reverse phase HPLC (45-80% MeCN/water w/0.1% TFA). The fractions containing the desired product were combined, partially concentrated to remove MeCN, diluted with saturated NaHCO3, and extracted with CH2Cl2 (2×). The combined organic layers were washed with brine, dried (MgSO4), filtered and evaporated to provide methyl 5-{1-hydroxy-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethyl}pyridine-2-carboxylate (111 mg, 0.215 mmol, 66% yield) as a colorless foam. MS ESI: [M+H]+ m/z 516.1.

1. customsealed
2. customCO was bubbled through the reaction mixture for 5 min
3. extractionextracted with EtOAc (2×)
4. washThe combined organic layers were washed with brine
5. dry with materialdried (MgSO4)
6. customevaporated
7. customThe crude material was purified by chromatography on silica gel (Biotage 25 g SNAP, 50-100% EtOAc/hexanes, 50-100% EtOAc/toluene)
8. additionThe fractions containing the desired product
9. concentrationpartially concentrated
10. customto remove MeCN
11. additiondiluted with saturated NaHCO3
12. extractionextracted with CH2Cl2 (2×)
13. washThe combined organic layers were washed with brine
14. dry with materialdried (MgSO4)
15. filtrationfiltered
16. customevaporated