4-Methyloxybenzyl chloride → 1-(4-Methoxybenzyl)-1H-indazole-6-carbaldehyde

HRID 1410336Notes

Reaction equation

HRID 1410336 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH:10]=[O:11])[CH:8]=2)[CH:3]=[N:2]1.CC([O-])(C)C.[K+].[CH3:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26]Cl)=[CH:22][CH:21]=1>CN(C=O)C>[CH3:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][N:1]2[C:9]3[C:4](=[CH:5][CH:6]=[C:7]([CH:10]=[O:11])[CH:8]=3)[CH:3]=[N:2]2)=[CH:22][CH:21]=1

Participants

5

Reactant 3

HCID 699934-Methyloxybenzyl chloride2×HCID 185383681H-Indazole-6-carbaldehydeHCID 23665647Potassium tert-butoxide

Product 1

HCID 866815121-(4-Methoxybenzyl)-1H-indazole-6-carbaldehydeYield 72%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1H-indazole-6-carbaldehyde (1.5 g, 10.3 mmol) in DMF (10 mL) at 0° C. was added KOtBu (1.4 g, 12.4 mmol) and let stir for 10 min. PMBCl (1.7 mL, 12.4 mmol) was then added and let slowly warm to room temperature. After 1.5 h the reaction was quenched with NH4Cl. The product was extracted with Et2O and the organic layers was washed brine and then dried over MgSO4. The solvent was removed and the crude material (mixture of N1 and N2 isomers) was dried under high vacuum. To the resulting residue was added PMBCl (0.70 mL, 5.15 mmol) and the mixture heated to 170° C. for 2.5 h. Cooled to room temperature and purified residue using Biotage Isolera (silica gel, 20-50% EtOAc in hexane) which gave the title compound (1.97 g, 72%). 1H NMR (400 MHz, CDCl3) δ 10.09 (s, 1H), 8.12 (s, 1H), 7.91 (s, 1H), 7.85 (d, J=8.4 Hz, 1H), 7.67 (d, J=8.4 Hz, 1H), 7.21 (d, J=8.5 Hz, 2H), 6.85 (d, J=8.6 Hz, 2H), 5.62 (s, 2H), 3.77 (s, 3H); MS ESI 266.9 [M+H]+, calcd for [C16H14N2O2+H]+ 267.1.

Workup

  1. customAfter 1.5 h the reaction was quenched with NH4Cl
  2. extractionThe product was extracted with Et2O
  3. washthe organic layers was washed brine
  4. dry with materialdried over MgSO4
  5. customThe solvent was removed
  6. customthe crude material (mixture of N1 and N2 isomers) was dried under high vacuum
  7. temperaturethe mixture heated to 170° C. for 2.5 h
  8. temperatureCooled to room temperature
  9. custompurified residue

Sources & evidence

ORD record
ord-82e4ac875b3b4dcb90f880731c57ad92
Source dataset
uspto-grants-2014_12
Patent number
US08921545B2

Reaction notes

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