تفاعل #160919

معادلة التفاعل

K3PO4

6-chloro-5-iodo-N-(4-(trifluoromethoxy)phenyl)nicotinamide

4-methyl-1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

→

title compound

6-Chloro-5-(4-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

المذيبات

dioxane

EtOAc

ظروف التفاعل

المعالجة

1. 1
   أخرىwas flushed with argon
2. 2
   أخرىThe vial was sealed
3. 3
   درجة الحرارةThe RM was cooled to RT
4. 4
   غسيلwashed with brine
5. 5
   تجفيفThe organic phase was dried over Na2SO4
6. 6
   أخرىthe solvent was evaporated off under reduced pressure
7. 7
   أخرىand the residue was purified by flash chromatography (RediSep® Silica gel column, n-heptane/EtOAc form 50% to 100% EtOAc)

الإجراء التجريبي

K3PO4 (127 mg, 0.6 mmol) was added to a solution of 6-chloro-5-iodo-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 4.2, 89 mg, 0.2 mmol) and 4-methyl-1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (58.4 mg, 0.2 mmol) in dioxane (1 mL) in a vial which was flushed with argon, heated to 110° C. and then PdCl2(dppf) (7.32 mg, 0.01 mmol) was added. The vial was sealed and the RM was stirred under argon at 110° C. for 18 h. The RM was cooled to RT, dissolved in EtOAc and washed with brine. The organic phase was dried over Na2SO4 and the solvent was evaporated off under reduced pressure. and the residue was purified by flash chromatography (RediSep® Silica gel column, n-heptane/EtOAc form 50% to 100% EtOAc) to afford the title compound as a white foam. HPLC (Condition 4) tR=6.24 min, UPLC-MS (Condition 3) tR=1.22 min, m/z=481.2 [M+H]+.

المصدر