반응 #160994

반응 방정식

1-(Tetrahydro-2H-pyran-2-yl)-1H-pyrazole-5-boronic acid pinacol ester

Na2CO3

6-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-iodonicotinamide

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title product

6-Chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)nicotinamide

용매

DME

반응 조건

후처리

1. 1
   기타The mixture was evacuated/purged 3 times with argon
2. 2
   workup.ADDITIONThe RM was diluted with EtOAc (350 mL)
3. 3
   세척washed with water (4×150 mL)
4. 4
   추출extracted with EtOAc
5. 5
   건조The combined extracts were dried over Na2SO4
6. 6
   기타the solvent was evaporated off under reduced pressure
7. 7
   기타to give the crude product which
8. 8
   기타was purified by flash chromatography (Silica gel column, 850 g, EtOAc/n-hexane (1:2))
9. 9
   기타crystallized from iPr2O/EtOAc

실험 절차

1-(Tetrahydro-2H-pyran-2-yl)-1H-pyrazole-5-boronic acid pinacol ester (9.45 g, 34.0 mmol), Na2CO3 (39.2 mL, 78 mmol) and PdCl2(dppf) (0.956 g, 1.307 mmol) were added to 6-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-iodonicotinamide (Stage 25.2, 12 g, 26.1 mmol) in DME (160 mL). The mixture was evacuated/purged 3 times with argon, and stirred at 80° C. for 22 h. The RM was diluted with EtOAc (350 mL), washed with water (4×150 mL) and extracted with EtOAc. The combined extracts were dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give the crude product which was purified by flash chromatography (Silica gel column, 850 g, EtOAc/n-hexane (1:2)) and crystallized from iPr2O/EtOAc to give the title product as a white solid. HPLC (Condition 5) tR=7.52 min, UPLC-MS (Condition 3) tR=1.22 min, m/z=483/485 [M+H]+.

출처