Potassium Hydroxide → 5-bromo-1-(4-methoxybenzyl)-3-{1-[4-(morpholin-4-ylcarbonyl)phenyl]-1H-1,2,3-triazol-4-yl}-1H-indazole

HRID 1520043Notes

Reaction equation

HRID 1520043 reaction equation
[CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:6]([CH2:7]Cl)=[CH:5][CH:4]=1.[Br:11][C:12]1[CH:13]=[C:14]2[C:18](=[CH:19][CH:20]=1)[NH:17][N:16]=[C:15]2[C:21]1[N:22]=[N:23][N:24]([C:26]2[CH:31]=[CH:30][C:29]([C:32]([N:34]3[CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)=[O:33])=[CH:28][CH:27]=2)[CH:25]=1.[OH-].[K+]>CC(C)=O.CN(C=O)C.Cl>[Br:11][C:12]1[CH:13]=[C:14]2[C:18](=[CH:19][CH:20]=1)[N:17]([CH2:7][C:6]1[CH:9]=[CH:10][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1)[N:16]=[C:15]2[C:21]1[N:22]=[N:23][N:24]([C:26]2[CH:27]=[CH:28][C:29]([C:32]([N:34]3[CH2:35][CH2:36][O:37][CH2:38][CH2:39]3)=[O:33])=[CH:30][CH:31]=2)[CH:25]=1

Participants

7

Reactant 3

HCID 14797Potassium HydroxideHCID 699934-Methyloxybenzyl chlorideHCID 574046585-bromo-3-{1-[4-(morpholin-4-ylcarbonyl)phenyl]-1H-1,2,3-triazol-4-yl}-1H-indazole

Product 1

HCID 679814615-bromo-1-(4-methoxybenzyl)-3-{1-[4-(morpholin-4-ylcarbonyl)phenyl]-1H-1,2,3-triazol-4-yl}-1H-indazoleYield 130%

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolvent

Procedure

4-methoxybenzylchloride (1.13 mL; 8.27 mmol; 1.5 eq.) was added dropwise to a solution of {4-[4-(5-Bromo-1H-indazol-3-yl)-[1,2,3]triazol-1-yl]-phenyl}-morpholin-4-yl-methanone (2.5 g; 5.5 mmol; 1.0 eq.) and KOH (0.34 g; 6.07 mmol; 1.1 eq.) in acetone (75 mL) and DMF (25 mL). The reaction mixture was stirred at RT O/N. It was then diluted with a 0.1N HCl solution and extracted three times with EtOAc. Combined organic phases were washed with brine, dried over magnesium sulfate, filtered and concentrated. The crude was purified by flash chromatography on silica (DCM:MeOH, gradient from 100:0 to 90:10) to give the title compound as an orange oil (4.1 g, 100%). UPLC/MS: (MS+) 573.0.

Workup

  1. extractionextracted three times with EtOAc
  2. washCombined organic phases were washed with brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude was purified by flash chromatography on silica (DCM:MeOH, gradient from 100:0 to 90:10)

Sources & evidence

ORD record
ord-53b02d0c54a648ce962b757681475400
Source dataset
uspto-grants-2015_07
Patent number
US09073892B2

Reaction notes

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