반응 #1833209

반응 방정식

water

pyridine

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

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

→

desired product

수율 89.0%

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

수율 89.0%

용매

CH2Cl2

반응 조건

후처리

1. 1
   workup.STIRRINGthe resulting mixture was stirred for five minutes
2. 2
   기타The mixture was transferred to a separatory funnel
3. 3
   기타the layers were separated
4. 4
   추출The aqueous phase was extracted with CH2Cl2 (3×50 mL)
5. 5
   건조the combined organic extracts were dried over sodium sulfate (Na2SO4)
6. 6
   여과filtered
7. 7
   농축concentrated in vacuo
8. 8
   기타The crude product was purified via normal phase flash chromatography (0% to 100% EtOAc/CH2Cl2)

실험 절차

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]+).

출처