反応 #978512

反応方程式

boronic acid

2-(2,2,2-trifluoroethyl)-4-chloro-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone

CsF

NH3

→

2-(2,2,2-trifluoroethyl)-4-(4-fluoro-3-methylphenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone

溶媒

DME

反応条件

後処理

1. 1
   その他was consumed
2. 2
   その他Volatiles were removed in vacuo
3. 3
   その他The residue was partitioned between water and ethyl acetate
4. 4
   洗浄The organic layer was washed with brine
5. 5
   乾燥dried over MgSO4
6. 6
   ろ過filtered
7. 7
   濃縮The filtrate was concentrated in vacuo
8. 8
   その他An off white powder was obtained (yield: 275 mg, 46%)

実験手順

The boronic acid (231 mg, 1.5 mmol), prepared in example 210A, 2-(2,2,2-trifluoroethyl)-4-chloro-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone (500 mg, 1.36 mmol), tetrakis-(triphenylphosphine)-palladium(0) (47 mg, 0.041 mmol), and CsF (413 mg, 2.72 mmol) were stirred at reflux in DME (20 mL) under N2 for 5 hours. TLC (1:1 hexanes/ethyl acetate) indicated that all the starting material was consumed. Volatiles were removed in vacuo. The residue was partitioned between water and ethyl acetate. The organic layer was washed with brine, dried over MgSO4, and filtered. The filtrate was concentrated in vacuo. An off white powder was obtained (yield: 275 mg, 46%). mp 88-91° C.; 1H NMR (300 MHz, CDCl3, a mixture of rotamers) δ 2.2, 2.25 (2d, J=1.5 Hz, 3H) 3.05, 3.09 (2 s, 3H) 4.78-4.92 (m, 2H) 6.61-6.8 (m, 1H) 6.82-6.98 (m, 1H) 7.35 (d, J=9 Hz, 1H) 7.78 (d, J=9 Hz, 1H) 7.86-8.09 (m, 4H). MS (DCI/NH3), m/z 441 (M+H)+. Anal. calc. for C20H16F4N2O3S.0.5H2O: C, 53.45; H, 3.81; N, 6.23. Found C, 53.17; H, 3.65; N, 5.88.

出典