Réaction #434693

Équation de réaction

3-fluoro-4-(5-isopropyl-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-4-yloxy)benzenamine

THF dichloromethane

sodium thiocyanate

4-fluorophenyl-acetyl chloride

→

title compound

Rendement 75.0%

1-(3-Fluoro-4-(5-isopropyl-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-4-yloxy)phenyl)-3-(2-(4-fluorophenyl)acetyl)thiourea

Rendement 75.0%

Solvants

ethyl acetate

Conditions de réaction

Traitement

1. 1
   workup.STIRRINGThe reaction mixture was stirred at ambient temperature for 16 h
2. 2
   Autrebefore being quenched with 1 N HCl
3. 3
   ExtractionThe solution was extracted with CH2Cl2 (3×50 ml)
4. 4
   Lavagethe combined organic fractions washed with 1 N NaOH (50 ml)
5. 5
   Séchagedried (Na2SO4)
6. 6
   Filtrationfiltered
7. 7
   Concentrationconcentrated in vacuo
8. 8
   AutrePurification by silica gel (Merck KGaA, 230–400 mesh particle size) flash chromatography
9. 9
   Lavageeluting with 4/1 hexane/ethyl acetate

Mode opératoire

To a homogeneous solution of sodium thiocyanate (0.037 g, 0.46 mmol, 3.3 equiv) in ethyl acetate (1 mL), at room temperature under a nitrogen atmosphere, was added 4-fluorophenyl-acetyl chloride (0.048 ml, 0.35 mmol, 2.5 equiv). The mixture was stirred for 2 h before being added directly to a homogeneous solution of 3-fluoro-4-(5-isopropyl-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-4-yloxy)benzenamine (0.040 g, 0.139 mmol, 1.0 equiv) in anhydrous 1/1 THF/dichloromethane (3 mL), under a nitrogen atmosphere. The reaction mixture was stirred at ambient temperature for 16 h before being quenched with 1 N HCl. The solution was extracted with CH2Cl2 (3×50 ml), the combined organic fractions washed with 1 N NaOH (50 ml), dried (Na2SO4), filtered and concentrated in vacuo. Purification by silica gel (Merck KGaA, 230–400 mesh particle size) flash chromatography, eluting with 4/1 hexane/ethyl acetate, afforded the title compound (0.050 g, 75%). 1H NMR (CDCl3) δ 12.34 (s, 1H), 8.47 (m, 1H), 7.65–7.78 (m, 2H), 7.63–7.64 (m, 1H), 7.19–7.32 (m, 4H) 703–7.08 (m, 2H), 6.66–6.67 (m, 1H), 3.65 (s, 2H), 3.40–3.50 (m, 1H), 1.28–1.30 (m, 6H); HRMS(ESI) 482.1462, calc, (M+H)+ 482.1461 found. Elemental Analysis: C24H21N5O2SF2. 0.23 H2O. calc: C, 59.35; H, 4.45, N, 14.42, found. C, 59.36; H, 4.44; N, 14.03.

Source