Potassium Carbonate → 1-(1-(3-(Pyrrolidin-1-yl)propyl)-1H-indazol-5-yl)-4-(4(trifluoromethyl)phenyl)pyridin-2(1H)-one

HRID 2390443Notes

Reaction equation

HRID 2390443 reaction equation
Cl[CH2:2][CH2:3][CH2:4][N:5]1[C:13]2[C:8](=[CH:9][C:10]([N:14]3[CH:19]=[CH:18][C:17]([C:20]4[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=4)=[CH:16][C:15]3=[O:30])=[CH:11][CH:12]=2)[CH:7]=[N:6]1.C([O-])([O-])=O.[K+].[K+].[NH:37]1[CH2:41][CH2:40][CH2:39][CH2:38]1>CN(C=O)C.O>[N:37]1([CH2:2][CH2:3][CH2:4][N:5]2[C:13]3[C:8](=[CH:9][C:10]([N:14]4[CH:19]=[CH:18][C:17]([C:20]5[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=5)=[CH:16][C:15]4=[O:30])=[CH:11][CH:12]=3)[CH:7]=[N:6]2)[CH2:41][CH2:40][CH2:39][CH2:38]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 31268PyrrolidineHCID 667191041-(1-(3-chloropropyl)-1H-indazol-5-yl)-4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one

Product 1

HCID 252062941-(1-(3-(Pyrrolidin-1-yl)propyl)-1H-indazol-5-yl)-4-(4(trifluoromethyl)phenyl)pyridin-2(1H)-oneYield 91.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

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 mixture 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 the intermediate 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 (78 mg, 0.18 mmol) in DMF (1.0 mL) was added K2CO3 (0.12 g, 0.90 mmol), pyrrolidine (130 mg, 1.8 mmol) and KI (30 mg, 0.18 mmol), and the reaction was heated to 50° C. for 18 h. The reaction mixture was cooled and diluted with H2O (25 mL). The resulting solids were collected by filtration and washed with H2O (10 mL). The collected solid was dissolved in EtOAc (20 mL) and washed with brine (10 mL). The washed organic solution was dried over Na2SO4, filtered and concentrated to provide the title compound (77 mg, 91%): 1H NMR (500 MHz, CDCl3) δ 8.05 (s, 1H), 7.77-7.74 (m, 5H), 7.60-7.42 (m, 3H), 6.92 (d, J=2.0 Hz, 1H), 6.53-6.51 (m, 1H), 4.51 (t, J=7.0 Hz, 2H), 2.48-2.44 (m, 6H), 2.16-2.12 (m, 2H), 1.79-1.77 (m, 4H).

Workup

  1. temperatureThe reaction mixture was cooled
  2. filtrationThe resulting solids were collected by filtration
  3. washwashed with H2O (10 mL)
  4. dissolutionThe collected solid was dissolved in EtOAc (20 mL)
  5. washwashed with brine (10 mL)
  6. dry with materialThe washed organic solution was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-fd709c2c33484d41a829e856ca239a29
Source dataset
uspto-grants-2012_09
Patent number
US08273770B2

Reaction notes

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