N-Methyl dicyclohexylamine → 7-Methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazole-5-carbaldehyde

HRID 501931Notes

Reaction equation

HRID 501931 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:11]=[O:12])[CH:5]=[C:6]2[C:10]=1[NH:9][N:8]=[CH:7]2.CN(C1CCCCC1)C1CCCCC1.[CH3:27][Si:28]([CH3:35])([CH3:34])[CH2:29][CH2:30][O:31][CH2:32]Cl>O1CCCC1>[CH3:1][C:2]1[C:10]2[C:6](=[CH:7][N:8]([CH2:32][O:31][CH2:30][CH2:29][Si:28]([CH3:35])([CH3:34])[CH3:27])[N:9]=2)[CH:5]=[C:4]([CH:11]=[O:12])[CH:3]=1

Participants

5

Reactant 3

HCID 24210N-Methyl dicyclohexylamineHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 184521067-Methyl-1H-indazole-5-carbaldehyde

Product 1

HCID 115728627-Methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazole-5-carbaldehyde

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 7-methyl-1H-indazole-5-carbaldehyde (5.0 g, 31.25 mmol) and N-methyl-dicyclohexylamine (113.5 mL, 62.35 mmol) in dry tetrahydrofuran (120 mL) at 0° C., was added 2-(trimethylsilyl)ethoxymethyl chloride (6.65 mL, 39.5 mmol). The icebath was removed and stirring continued for 5 h. The reaction mixture was diluted with ethyl acetate, washed with water (2×), brine (2×), dried over sodium sulfate, and concentrated in vacuo. Column chromatography afforded 8.5 g (93%). 1H-NMR (CD3OD, 300 MHz) δ −0.04 (s, 9H), 0.83-1.01 (m, 2H), 2.60 (s, 3H), 3.22-3.34 (m, 2H), 3.60-3.76 (m, 2H), 5.58 (s, 2H), 7.54 (s, 1H), 8.23 (s, 1H), 8.64 (s, 1H), 9.91 (s, 1H). Mass spec.: 291.33 (MH)+.

Workup

  1. customThe icebath was removed
  2. additionThe reaction mixture was diluted with ethyl acetate
  3. washwashed with water (2×), brine (2×)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customColumn chromatography afforded 8.5 g (93%)

Sources & evidence

ORD record
ord-4bd1d4f4aa2c4c4c9ce85bf16bf79934
Source dataset
uspto-grants-2010_08
Patent number
US07772244B2

Reaction notes

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