Methyl iodide → ethyl 7-methoxy-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxylate

HRID 711068Notes

Reaction equation

HRID 711068 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH:5]=[C:6]2[C:10]=1[N:9]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)[N:8]=[CH:7]2.[C:22](=O)([O-])[O-].[K+].[K+].CI>CN(C)C=O.O>[CH3:22][O:1][C:2]1[CH:3]=[C:4]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH:5]=[C:6]2[C:10]=1[N:9]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)[N:8]=[CH:7]2

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 66920492Ethyl 7-hydroxy-1-tetrahydropyran-2-YL-indazole-5-carboxylate

Product 1

HCID 66920406ethyl 7-methoxy-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxylateYield 101.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of ethyl 7-hydroxy-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxylate (WO2009144554) (100 mg, 0.34 mmol) and potassium carbonate (95.1 mg, 0.68 mmol) in N,N-dimethylformamide (1 mL) was added methyl iodide (32 μL, 0.51 mmol). The reaction was stirred at room temperature overnight. The reaction was diluted with water and extracted with ethyl acetate (4×). The combined organic layers were washed with water and brine, dried over sodium sulfate, filtered, and concentrated to give the title compound (105 mg, 100%) as a yellow oil. +ESI (M+1-THP) 221.2; 1H NMR (400 MHz, CDCl3, δ): 8.07-8.10 (m, 2H), 7.43 (d, J=0.98 Hz, 1H), 6.24 (dd, J=10.24, 2.44 Hz, 1H), 4.38 (q, J=7.15 Hz, 2H), 4.08 (dt, J=11.56, 2.02 Hz, 1H), 4.04 (s, 3H), 3.70-3.78 (m, 1H), 2.54-2.66 (m, 1H), 2.09-2.19 (m, 1H), 2.01-2.08 (m, 1H), 1.71-1.83 (m, 2H), 1.55-1.64 (m, 1H), 1.41 (t, J=7.12 Hz, 3H).

Workup

  1. extractionextracted with ethyl acetate (4×)
  2. washThe combined organic layers were washed with water and brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-46eca87e22b743b5b37de12e948eda51
Source dataset
uspto-grants-2015_11
Patent number
US09181252B2

Reaction notes

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