Cesium carbonate → 5-Bromo-1-(2-(pyrrolidin-1-yl)ethyl)-3-(trifluoromethyl)-1H-indazole

HRID 2387523Notes

Reaction equation

HRID 2387523 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[C:5]2[C:11]([F:14])([F:13])[F:12].C([O-])([O-])=O.[Cs+].[Cs+].Cl.Cl[CH2:23][CH2:24][N:25]1[CH2:29][CH2:28][CH2:27][CH2:26]1>CS(C)=O.O>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:23][CH2:24][N:25]1[CH2:29][CH2:28][CH2:27][CH2:26]1)[N:6]=[C:5]2[C:11]([F:14])([F:13])[F:12]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 816681-(2-Chloroethyl)pyrrolidine hydrochlorideHCID 178506287HCID 178506287, compound

Product 1

HCID 592934135-Bromo-1-(2-(pyrrolidin-1-yl)ethyl)-3-(trifluoromethyl)-1H-indazoleYield 65%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

A solution of 5-bromo-3-(trifluoromethyl)-1H-indazole (282 mg, 1.07 mmol) in DMSO (15 mL) was treated with Cs2CO3 (1.45 g, 4.45 mmol) and 1-(2-chloroethyl)pyrrolidine hydrochloride (376 mg, 2.21 mmol). After stirring for 16 hours at room temperature, the mixture was diluted with water (50 mL) and extracted with EtOAc (3×50 mL). The combined organics were washed with brine (50 mL), dried over Na2SO4, filtered and concentrated to dryness. Purification by flash column chromatography (silica gel, MeOH/EtOAc/hexanes, 0:1:1 to 1.49:50) gave the title compound (250 mg, 65%) as a light yellow oil: 1H NMR (500 MHz, CDCl3) δ 7.98 (s, 1H), 7.54 (dd, J=8.9, 1.7 Hz, 1H), 7.40 (d, J=8.9, 1H), 4.54 (t, J=7.1 Hz, 2H), 3.01 (t, J=7.1 Hz, 2H), 2.56-2.54 (m, 4H), 1.79-1.75 (m, 4H); ESI MS m/z 362 [M+H]+.

Workup

  1. extractionextracted with EtOAc (3×50 mL)
  2. washThe combined organics were washed with brine (50 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated to dryness
  6. customPurification by flash column chromatography (silica gel, MeOH/EtOAc/hexanes, 0:1:1 to 1.49:50)

Sources & evidence

ORD record
ord-8a07f5930d9c430ab97c3d7b9c35b2b8
Source dataset
uspto-grants-2012_09
Patent number
US08268868B2

Reaction notes

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