Cesium carbonate → (S)-1-(1-(oxiran-2-ylmethyl)-1H-indazol-5-yl)-4-(4-(trifluoromethyl)phenyl)-pyridin-2(1H)-one

HRID 2390448Notes

Reaction equation

HRID 2390448 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([N:10]3[CH:15]=[CH:14][C:13]([C:16]4[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=4)=[CH:12][C:11]3=[O:26])=[CH:7][CH:8]=2)[CH:3]=[N:2]1.S(C1C=CC([N+]([O-])=O)=CC=1)(O[CH2:31][C@@H:32]1[O:34][CH2:33]1)(=O)=O.C(=O)([O-])[O-].[Cs+].[Cs+]>CS(C)=O.O>[O:34]1[CH2:33][C@@H:32]1[CH2:31][N:1]1[C:9]2[C:4](=[CH:5][C:6]([N:10]3[CH:15]=[CH:14][C:13]([C:16]4[CH:21]=[CH:20][C:19]([C:22]([F:24])([F:25])[F:23])=[CH:18][CH:17]=4)=[CH:12][C:11]3=[O:26])=[CH:7][CH:8]=2)[CH:3]=[N:2]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 14292098(R)-(-)-Glycidyl-4-nitrobenzenesulfonateHCID 576255401-(1H-indazol-5-yl)-4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one

Product 1

HCID 57625522(S)-1-(1-(oxiran-2-ylmethyl)-1H-indazol-5-yl)-4-(4-(trifluoromethyl)phenyl)-pyridin-2(1H)-oneYield 55.3%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

A mixture of 1-(1H-indazol-5-yl)-4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one (750 mg, 2.11 mmol), (R)-(−)-glycidyl nosylate (657 mg, 2.53 mmol) and cesium carbonate (1.03 g, 3.17 mmol) in methyl sulfoxide (6 mL) was stirred at ambient temperature overnight. The reaction mixture was diluted with water (20 mL) and extracted with ethyl acetate (2×50 mL). The combined organic extracts were washed with brine (20 mL), dried (Na2SO4), and concentrated under reduced pressure. Purification by column chromatography (silica gel, ethyl acetate) gave the title compound (480 mg, 55%) as a yellow solid: 1H NMR (300 MHz, CDCl3) δ 8.09 (d, J=0.9 Hz, 1H), 7.76-7.72 (m, 5H), 7.65 (d, J=9.0 Hz, 1H), 7.52 (d, J=7.2 Hz, 1H), 7.47 (dd, J=9.0, 2.1 Hz, 1H), 6.92 (d, J=1.8 Hz, 1H), 6.53 (dd, J=6.9, 1.8 Hz, 1H), 4.79 (dd, J=15, 3.0 Hz, 1H), 4.48 (dd, J=15.3, 5.7 hz, 1H), 3.41-3.37 (m, 1H), 2.88 (app t, J=4.5 Hz, 1H), 2.60 (dd, J=4.5, 2.4 Hz, 1H).

Workup

  1. extractionextracted with ethyl acetate (2×50 mL)
  2. washThe combined organic extracts were washed with brine (20 mL)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated under reduced pressure
  5. customPurification by column chromatography (silica gel, ethyl acetate)

Sources & evidence

ORD record
ord-c316d430c2b748789872edafe4445570
Source dataset
uspto-grants-2012_09
Patent number
US08273770B2

Reaction notes

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