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

HRID 338457Notes

Reaction equation

HRID 338457 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 0.5N 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-6504a466430b4beead312fd2420a6814
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Reaction notes

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