반응 #682492

반응 방정식

hydrochloric acid

cesium fluoride

(trifluoromethyl)trimethylsilane

cesium fluoride

(Trifluoromethyl)trimethylsilane

1-(4-(3-((4-(difluoromethyl)pyrimidin-2-yl)amino)-5-methylphenyl)-1H-pyrazol-1-yl)propan-2-one

→

racemic 3-(4-(3-((4-(difluoromethyl)pyrimidin-2-yl)amino)-5-methylphenyl)-1H-pyrazol-1-yl)-1,1,1-trifluoro-2-methylpropan-2-ol

용매

DMSO water

THF

반응 조건

후처리

1. 1
   workup.STIRRINGThe reaction was stirred for 18 hours
2. 2
   여과filtered through a plug of glass wool
3. 3
   workup.STIRRINGstirred for 30 minutes
4. 4
   농축The reaction was concentrated under reduced pressure
5. 5
   기타to afford the crude product residue
6. 6
   기타purified by mass triggered reverse phase HPLC (ACN/water+0.1% TFA)

실험 절차

(Trifluoromethyl)trimethylsilane (0.103 ml, 0.70 mmol) was added to a 20° C. solution of 1-(4-(3-((4-(difluoromethyl)pyrimidin-2-yl)amino)-5-methylphenyl)-1H-pyrazol-1-yl)propan-2-one (100 mg, 0.28 mmol) and cesium fluoride (4.3 mg, 0.028 mmol) in THF (1 mL). The reaction was allowed to stir for 60 minutes at room temperature and additional cesium fluoride (4.25 mg, 0.03 mmol) and (trifluoromethyl)trimethylsilane (0.103 ml, 0.70 mmol) were then added. The reaction was stirred for 18 hours and filtered through a plug of glass wool. The filtrate was treated with hydrochloric acid (6N, 1 mL, 6 mmol) and stirred for 30 minutes. The reaction was concentrated under reduced pressure to afford the crude product residue. The crude product residue was dissolved in DMSO/water and purified by mass triggered reverse phase HPLC (ACN/water+0.1% TFA) to afford racemic 3-(4-(3-((4-(difluoromethyl)pyrimidin-2-yl)amino)-5-methylphenyl)-1H-pyrazol-1-yl)-1,1,1-trifluoro-2-methylpropan-2-ol. MS ESI calcd. for C19H19F5N5O [M+H]+ 428. found 428. The racemic mixture was purified by chiral SFC (Chiralpak, IA, 21×250 (mm), 70 mL/min, 25% Methanol/CO2) to afford (S or R)-3-(4-(3-((4-(difluoromethyl)pyrimidin-2-yl)amino)-5-methylphenyl)-1H-pyrazol-1-yl)-1,1,1-trifluoro-2-methylpropan-2-ol

출처