Cesium carbonate → 2-{4-[(2,3-difluorobenzyl)oxy]phenyl}-N-[1-(2-pyrrolidin-1-ylethyl)-1H-indazol-4-yl]acetamide

HRID 1790092Notes

Reaction equation

HRID 1790092 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([NH:11][C:12]2[CH:20]=[CH:19][CH:18]=[C:17]3[C:13]=2[CH:14]=[N:15][N:16]3[CH2:21][CH2:22][N:23]2[CH2:27][CH2:26][CH2:25][CH2:24]2)=[O:10])=[CH:4][CH:3]=1.Br[CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[C:31]=1[F:37].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[F:37][C:31]1[C:32]([F:36])=[CH:33][CH:34]=[CH:35][C:30]=1[CH2:29][O:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([NH:11][C:12]2[CH:20]=[CH:19][CH:18]=[C:17]3[C:13]=2[CH:14]=[N:15][N:16]3[CH2:21][CH2:22][N:23]2[CH2:27][CH2:26][CH2:25][CH2:24]2)=[O:10])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 5179841-(Bromomethyl)-2,3-difluoro-benzeneHCID 220365922-(4-hydroxy-phenyl)-N-[1-(2-pyrrolidin-1-yl-ethyl)-1H-indazol-4-yl]-acetamide

Product 1

HCID 113752572-{4-[(2,3-difluorobenzyl)oxy]phenyl}-N-[1-(2-pyrrolidin-1-ylethyl)-1H-indazol-4-yl]acetamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-(4-hydroxy-phenyl)-N-[1-(2-pyrrolidin-1-yl-ethyl)-1H-indazol-4-yl]-acetamide (45.0 mg, 0.124 mmol), 1-bromomethyl-2,3-difluoro-benzene (38.0 mg, 0.185 mmol), Cs2CO3 (60.0 mg, 0.184 mmol) in 2 mL of DMF was shaken for 6 hours after which the mixture was concentrated under reduced pressure. The residue was dissolved in 1.5 mL of a 1:1 mixture of dimethyl sulfoxide/MeOH and purified by preparative reverse-phase HPLC. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.61 (m, 4H), 2.44 (m, 4H), 2.86 (t, 2H, J=6.78), 3.72 (s, 2H), 4.47 (t, 2H, J=6.78), 5.18 (s, 2H), 7.00 (m, 2H), 7.19–7.72 (m, 8H), 8.26 (s, 1H), 10.16 (s, 1H); MS (DCI/NH3) m/z 491 [M+H]+.

Workup

  1. concentrationwas concentrated under reduced pressure
  2. dissolutionThe residue was dissolved in 1.5 mL of a 1:1 mixture of dimethyl sulfoxide/MeOH
  3. custompurified by preparative reverse-phase HPLC

Sources & evidence

ORD record
ord-f9d91439e9bb4de78088195624bbb089
Source dataset
uspto-grants-2006_07
Patent number
US07071182B2

Reaction notes

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