Sodium hydride → HCID 67293404, compound

HRID 1038817Notes

Reaction equation

HRID 1038817 reaction equation
[H-].[Na+].[N+:3]([C:6]1[CH:14]=[C:13]2[C:9]([C:10]([CH:15]=O)=[N:11][NH:12]2)=[CH:8][CH:7]=1)([O-:5])=[O:4].[CH3:17][Si:18]([CH2:21][CH2:22][O:23][CH2:24]Cl)([CH3:20])[CH3:19].[NH4+].[Cl-]>O.C1COCC1>[CH3:15][C:10]1[C:9]2[C:13](=[CH:14][C:6]([N+:3]([O-:5])=[O:4])=[CH:7][CH:8]=2)[N:12]([CH2:24][O:23][CH2:22][CH2:21][Si:18]([CH3:20])([CH3:19])[CH3:17])[N:11]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 178520046HCID 178520046, compound

Product 1

HCID 67293404HCID 67293404, compoundYield 52.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a flask was added NaH (60% in mineral oil, 0.473 g, 11.8 mmol) and THF (59.1 mL). The mixture was cooled to about 0° C. 6-Nitro-1H-indazole-3-carbaldehyde (2.26 g, 11.8 mmol, ChemPacific) was added in several smaller portions and the mixture was stirred at about 0° C. for about 20 min. SEMCl (2.30 mL, 13.0 mmol) was added dropwise and the mixture was stirred at about 0° C. for about 10 min and then stirred at rt for about 72 h. To the mixture was added saturated aqueous NH4Cl (25 mL) and water (10 mL). The aqueous layer was separated and extracted with DCM (2×50 mL). The combined organic layers were washed with brine (20 mL), dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (80 g silica gel) eluting with 10 to 25% EtOAc/heptane to give 3-methyl-6-nitro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole (1.915 g, 50%): 1H NMR (400 MHz, DMSO) δ 10.24 (s, 1H), 8.94 (d, J=1.5 Hz, 1H), 8.36 (dd, J=6.5, 2.3 Hz, 1H), 8.31-8.13 (m, 1H), 6.08 (s, 2H), 3.58 (s, 2H), 0.83 (s, 2H), −0.12 (s, 9H).

Workup

  1. stirringthe mixture was stirred at about 0° C. for about 10 min
  2. stirringstirred at rt for about 72 h
  3. customThe aqueous layer was separated
  4. extractionextracted with DCM (2×50 mL)
  5. washThe combined organic layers were washed with brine (20 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by column chromatography (80 g silica gel)
  10. washeluting with 10 to 25% EtOAc/heptane

Sources & evidence

ORD record
ord-0c03062106574c5694395ead7600d66d
Source dataset
uspto-grants-2013_10
Patent number
US08551981B2

Reaction notes

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