Réaction #682750

Équation de réaction

2-(4-(difluoromethyl)phenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide

2-chloro-11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole

Na2CO3

X-Phos

→

2-(4-(difluoromethyl)phenyl)-5-(11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

Rendement 43.0%

Solvants

1,4-dioxane

H2O

Conditions de réaction

Traitement

1. 1
   TempératureThe reaction mixture was cooled to RT
2. 2
   Filtrationfiltered
3. 3
   LavageThe filtrate was washed with H2O
4. 4
   Séchagedried over Na2SO4
5. 5
   ConcentrationAfter being concentrated
6. 6
   Autrethe residue was purified by prep-HPLC

Mode opératoire

To a degassed solution of 2-(4-(difluoromethyl)phenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (100 mg, 0.18 mmol), 2-chloro-11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole (50 mg, 0.20 mmol), Na2CO3 (39 mg, 0.37 mmol), in 1,4-dioxane (3 mL) and H2O (0.1 mL) were added Pd2(dba)3 (5 mg) and X-Phos (5 mg) under N2. Then the mixture was stirred at 100° C. for 2 hours. The reaction mixture was cooled to RT and filtered. The filtrate was washed with H2O and dried over Na2SO4. After being concentrated, the residue was purified by prep-HPLC to give the product of 2-(4-(difluoromethyl)phenyl)-5-(11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (50 mg, yield: 41%). 1H-NMR (CDCl3, 400 MHz) δ 8.08 (d, J=7.6 Hz, 2H), 8.05 (s, 1H), 7.73 (s, 1H), 7.69 (d, J=8.0 Hz, 2H), 7.53 (s, 2H), 7.30 (s, 1H), 7.25 (d, J=2.8 Hz, 1H), 7.16 (d, J=8.0 Hz, 1H), 6.88˜6.93 (m, 1H), 6.75 (s, 1H), 6.09 (d, J=4.4 Hz, 1H), 6.04 (s, 2H), 3.41 (s, 3H), 3.04 (d, J=4.8 Hz, 3H), 2.79 (s, 3H). MS (M+H)+: 647.

Source