反応 #1833209

反応方程式

water

pyridine

3-((3,3,3-trifluoropropyl)thio) propanoyl chloride

3-chloro-N-ethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine

→

desired product

収率 89.0%

N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)thio)propanamide

収率 89.0%

溶媒

CH2Cl2

反応条件

後処理

1. 1
   workup.STIRRINGthe resulting mixture was stirred for five minutes
2. 2
   その他The mixture was transferred to a separatory funnel
3. 3
   その他the layers were separated
4. 4
   抽出The aqueous phase was extracted with CH2Cl2 (3×50 mL)
5. 5
   乾燥the combined organic extracts were dried over sodium sulfate (Na2SO4)
6. 6
   ろ過filtered
7. 7
   濃縮concentrated in vacuo
8. 8
   その他The crude product was purified via normal phase flash chromatography (0% to 100% EtOAc/CH2Cl2)

実験手順

To a solution of 3-chloro-N-ethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine (prepared as described in the U.S. Publication No. 2012/0110702 to Yap et al.) (10 g, 44.9 mmol) in CH2Cl2 (100 mL) at a temperature of about 0° C. and under N2 was added pyridine (5.45 mL, 67.4 mmol), 4-dimethylaminopyridine (DMAP) (2.74 g, 22.45 mmol), and 3-((3,3,3-trifluoropropyl)thio) propanoyl chloride (9.91 g, 44.9 mmol), sequentially. The reaction was warmed to room temperature and stirred for one hour. The reaction mixture was poured into water (100 mL), and the resulting mixture was stirred for five minutes. The mixture was transferred to a separatory funnel, and the layers were separated. The aqueous phase was extracted with CH2Cl2 (3×50 mL), and the combined organic extracts were dried over sodium sulfate (Na2SO4), filtered, and concentrated in vacuo. The crude product was purified via normal phase flash chromatography (0% to 100% EtOAc/CH2Cl2) to provide the desired product as a pale yellow solid (17.21 g, 89%): IR (thin film) 1659 cm−1; 1H NMR (400 MHz, CDCl3) δ 8.95 (d, J=2.6 Hz, 1H), 8.63 (dd, J=4.7, 1.3 Hz, 1H), 8.05 (ddd, J=8.3, 2.7, 1.4 Hz, 1H), 7.96 (s, 1H), 7.47 (dd, J=8.3, 4.8 Hz, 1H), 3.72 (q, J=7.1 Hz, 2H), 2.84 (t, J=7.2 Hz, 2H), 2.66 (m, 2H), 237 (t, J=7.2 Hz, 2H), 2.44 (m, 2H), 1.17 (t, J=7.2 Hz, 3H); ESIMS m/z 409 ([M+2H]+).

出典