Sodium Hydroxide → 5-Bromo-6-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazole

HRID 1054800Notes

Reaction equation

HRID 1054800 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[CH3:11])[NH:7][N:6]=[CH:5]2.C1(C(N)C2CCCCC2)CCCCC1.[CH3:26][Si:27]([CH2:30][CH2:31][O:32][CH2:33]Cl)([CH3:29])[CH3:28].[OH-].[Na+]>C1COCC1.CCOC(C)=O>[Br:1][C:2]1[C:10]([CH3:11])=[CH:9][C:8]2[C:4](=[CH:5][N:6]([CH2:33][O:32][CH2:31][CH2:30][Si:27]([CH3:29])([CH3:28])[CH3:26])[N:7]=2)[CH:3]=1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 10774245alpha-CyclohexylcyclohexanemethanamineHCID 247292595-Bromo-6-methyl-1H-indazole

Product 1

HCID 866987925-Bromo-6-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazoleYield 79%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-bromo-6-methyl-indazole (500 mg, 2.37 mmol) in THF (6 mL) was added dicyclohexylmethylamine (0.63 mL, 3.0 mmol), followed by SEM-chloride (0.50 mL, 2.8 mmol) via syringe. The reaction mixture was stirred at room temperature for 3 hours. EtOAc (20 mL) was added followed by 0.5 N aqueous NaOH (15 mL). The layers were separated and the aqueous layer was extracted with EtOAc (3×20 mL). The combined organic layers were washed consecutively with water and brine. The organic layer was dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (0-33% EtOAc/heptane) to provide the title compound (639 mg, 79% yield). MS (ES+) 343.1 (M+H)+. 1H NMR (500 MHz, CDCl3) δ 8.03 (s, 1H), 7.93 (s, 1H), 7.60 (s, 1H), 5.70 (s, 2H), 3.62 (t, J=8.10 Hz, 2H), 2.52 (s, 3H), 0.95 (t, J=8.30 Hz, 2H), 0.00 (s, 9H).

Workup

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted with EtOAc (3×20 mL)
  3. washThe combined organic layers were washed consecutively with water and brine
  4. dry with materialThe organic layer was dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by flash chromatography (0-33% EtOAc/heptane)

Sources & evidence

ORD record
ord-5445a7e825dd451db2a42bf15389d42d
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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