反応 #679541

反応方程式

BF4

2-(2-ethynylphenyl)butanamide

Et3N

tert-butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

→

title compound A1

収率 68.2%

tert-Butyl 4-(4-((4-((2-(1-amino-1-oxobutan-2-yl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

収率 68.2%

溶媒

DMF

反応条件

後処理

1. 1
   その他The volatiles were removed under reduced pressure
2. 2
   その他then purified by column chromatography (Biotage Isolera, SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.)

実験手順

A mixture of tert-butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (K3) (193 mg, 0.422 mmol), PdCl2(PPh3)2 (15 mg, 0.021 mmol), t-Bu3PH.BF4 (6 mg, 0.021 mmol), CuI (4 mg, 0.021 mmol) and 2-(2-ethynylphenyl)butanamide (K1) (87 mg, 0.47 mmol) in DMF (3.0 mL) was degassed with nitrogen for 10 minutes. Et3N (1.0 mL) was added and the resulting mixture was heated under microwave irradiation at 120° C. for 20 minutes. The volatiles were removed under reduced pressure and the residue was adsorbed onto silica gel then purified by column chromatography (Biotage Isolera, SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.) to give the title compound A1 as a yellow solid (175 mg, 68%); 1H NMR (400 MHz, d6-DMSO) δ 10.39 (s, 1H), 8.88-8.76 (m, 1H), 7.67 (d, J=8.5 Hz, 2H), 7.63-7.47 (m, 3H), 7.37 (td, J=7.4, 1.6 Hz, 1H), 7.27-7.17 (m, 3H), 7.01 (s, 1H), 4.07 (s, 2H), 3.89 (dd, J=8.6, 6.4 Hz, 1H), 2.80 (br, 2H), 2.64 (J m, 1H), 1.98-1.90 (m, 1H), 1.74 (d, J=12.7 Hz, 2H), 1.70-1.60 (m, 1H), 1.55-1.44 (m, 2H), 1.42 (s, 9H), 0.87 (t, J=7.3 Hz, 3H). LCMS-A: rt 6.726 min; m/z 606 [M−H]−.

出典