1-Bromo-3-chloropropane → 1-(1-(3-chloropropyl)-1H-indazol-5-yl)-4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one

HRID 2390441Notes

Reaction equation

HRID 2390441 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][CH2:30][Cl:31].C([O-])([O-])=O.[Cs+].[Cs+]>CS(C)=O.O>[Cl:31][CH2:30][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 80061-Bromo-3-chloropropaneHCID 10796Cesium carbonateHCID 576255401-(1H-indazol-5-yl)-4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one

Product 1

HCID 667191041-(1-(3-chloropropyl)-1H-indazol-5-yl)-4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one

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 (278 mg, 0.783 mmol) in DMSO (4.0 mL) was added 3-bromo-1-chloropropane (1.23 g, 7.83 mmol) and Cs2CO3 (765 mg, 2.35 mmol), and the reaction was stirred at ambient temperature for 18 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 (silica gel, CH2Cl2/MeOH, 100:1) yielded 1-(1-(3-chloropropyl)-1H-indazol-5-yl)-4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one. To a solution of 1-(1-(3-chloropropyl)-1H-indazol-5-yl)-4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one (84 mg, 0.19 mmol) in DMF (1.0 mL) was added K2CO3 (0.13 g, 0.97 mmol), dimethylamine (1.94 mL, 3.88 mmol, 2.0 M in THF) and KI (32 mg, 0.19 mmol), and the reaction was heated to 45° C. for 18 h. The reaction mixture was cooled, diluted with H2O (25 mL) and extracted with EtOAc (3×25 mL). The combined organic extracts were washed with brine (25 mL), dried over Na2SO4, filtered and concentrated. Flash chromatography (Biotage 25+M column, CH2Cl2/MeOH/NH4OH, 50:1:0 to 20:1:0.1) provided the title compound (54 mg, 63%): 1H NMR (500 MHz, CDCl3) δ 8.06 (s, 1H), 7.75-7.70 (m, 5H), 7.60-7.43 (m, 3H), 6.92-6.91 (m, 1H), 6.53-6.51 (m, 1H), 4.49 (t, J=6.8 Hz, 2H), 2.29 (t, J=6.8 Hz, 2H), 2.23 (s, 6H), 2.13-2.08 (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-d459c185c90b41bdbdfe9a054f897008
Source dataset
uspto-grants-2012_09
Patent number
US08273770B2

Reaction notes

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