1-Bromo-2-Chloroethane → 1-(1-(2-Chloroethyl)-1H-indazol-5-yl)-4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one

HRID 2390440Notes

Reaction equation

HRID 2390440 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.Br[CH2:28][CH2:29][Cl:30].C([O-])([O-])=O.[Cs+].[Cs+]>CS(C)=O.O>[Cl:30][CH2:29][CH2:28][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 78491-Bromo-2-ChloroethaneHCID 10796Cesium carbonateHCID 576255401-(1H-indazol-5-yl)-4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one

Product 1

HCID 576255391-(1-(2-Chloroethyl)-1H-indazol-5-yl)-4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-oneYield 51%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

To a solution of 1-(1H-indazol-5-yl)-4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one (120 mg, 0.338 mmol) in DMSO (2.0 mL) was added 2-bromo-1-chloroethane (485 mg, 3.38 mmol) and Cs2CO3 (330 mg, 1.01 mmol), and the reaction was stirred at ambient temperature for 3 h. The reaction was diluted with H2O (25 mL) and extracted with EtOAc (3×25 mL). The extracts were washed with brine (25 mL), dried over Na2SO4, and concentrated. Flash chromatography (Biotage 25+M column, CH2Cl2/MeOH, 99:1 to 98:2) yielded the title compound (72 mg, 51%): 1H NMR (500 MHz, CDCl3) δ 8.11 (s, 1H), 7.76-7.73 (m, 5H), 7.59-7.47 (m, 3H), 6.92-6.91 (m, 1H), 6.53-6.51 (m, 1H), 4.74-4.71 (m, 2H), 4.00-3.98 (m, 2H).

Workup

  1. extractionextracted with EtOAc (3×25 mL)
  2. washThe extracts were washed with brine (25 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-3991ac8257884887a5e0d0a1713fb2dd
Source dataset
uspto-grants-2012_09
Patent number
US08273770B2

Reaction notes

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