Cesium carbonate → 1-(4-methoxybenzyl)-1H-indazole-3-carbonitrile

HRID 1776388Notes

Reaction equation

HRID 1776388 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:10]#[N:11])=[N:2]1.Br[CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[CH3:21][O:20][C:17]1[CH:18]=[CH:19][C:14]([CH2:13][N:1]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[C:3]([C:10]#[N:11])=[N:2]2)=[CH:15][CH:16]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 1650214-Methoxybenzyl bromideHCID 4375561H-Indazole-3-carbonitrile

Product 1

HCID 867324141-(4-methoxybenzyl)-1H-indazole-3-carbonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

6.47 g of 1H-indazole-3-carbonitrile (45.2 mmol, 1 eq.) were dissolved in 65 ml of dry DMF. 10 g of 1-(bromomethyl)-4-methoxybenzene (49.7 mmol, 1.1 eq.) and 17.7 g of cesium carbonate (54.2 mmol, 1.2 eq.) were added. The mixture was stirred at room temperature for 18 hours under nitrogen atmosphere. Then the reaction mixture was partitioned between water and tert-butyl methyl ether. The separated aqueous layer was extracted twice with tert-butyl methyl ether. The combined organic layers were washed with brine, dried over magnesium sulfate and concentrated in vacuo. The crystallization from methanol provided 9.25 g (35.1 mmol, 77.7%) of analytically pure target compound.

Workup

  1. customThen the reaction mixture was partitioned between water and tert-butyl methyl ether
  2. extractionThe separated aqueous layer was extracted twice with tert-butyl methyl ether
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe crystallization from methanol
  7. customprovided 9.25 g (35.1 mmol, 77.7%) of analytically pure target compound

Sources & evidence

ORD record
ord-0d81d44dd6e345a8b95981bc723cec31
Source dataset
uspto-grants-2016_02
Patent number
US09265763B2

Reaction notes

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