تفاعل #70590

معادلة التفاعل

5-(2-phenoxypyrimidin-5-yl)-1H-pyrazole-3-carboxylic acid

1-methylpiperazine

triethylamine

→

title compound

المردود 60.1%

(4-methylpiperazin-1-yl)(5-(2-phenoxypyrimidin-5-yl)-1H-pyrazol-3-yl)methanone

المردود 60.1%

المذيبات

thionyl chloride

dichloromethane

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةThe solution was heated
2. 2
   درجة الحرارةto reflux for four hours
3. 3
   أخرىThionyl chloride was evaporated under reduced pressure and to the residue
4. 4
   workup.ADDITIONwas added toluene (2×30 mL), which
5. 5
   أخرىwas evaporated
6. 6
   أخرىto remove residual thionyl chloride
7. 7
   أخرىThe solvent was evaporated
8. 8
   أخرىthe residue was purified by silica gel flash chromatography

الإجراء التجريبي

To a solution consisting of 5-(2-phenoxypyrimidin-5-yl)-1H-pyrazole-3-carboxylic acid (Example 56, 60 mg, 0.21 mmol) in thionyl chloride (10 mL) was added one drop of dry DMF. The solution was heated to reflux for four hours and was subsequently allowed to cool to room temperature. Thionyl chloride was evaporated under reduced pressure and to the residue was added toluene (2×30 mL), which was evaporated and the residue subjected to high vacuum to remove residual thionyl chloride. The residue and 1-methylpiperazine (25 mg, 0.028 mL, 0.25 mmol) were dissolved in dichloromethane (10 mL) followed by the addition of triethylamine (0.14 mL). The solution was stirred at room temperature for 18 hours. The solvent was evaporated and the residue was purified by silica gel flash chromatography using 0-10% methanol in dichloromethane gradient through a 25-g Silicycle® flash silica cartridge to afford the title compound as a white solid (46 mg, 60% yield); Rf 0.30 with 6% methanol in dichloromethane; 1H-NMR (300 MHz; CD3OD) δ 8.96 (s, 2H), 7.43 (m, 2H), 7.25 (m, 1H), 7.19 (d, 2H), 7.02 (s, 1H), 3.74-3.99 (br, 4H), 2.51 (br, 4H), 2.33 (s, 3H); MS (ESI−) m/z 363 (M−1); H-PGDS FPBA IC50: 0.65 μM; H-PGDS inhibitor EIA IC50: 0.42 μM.

المصدر