3-Bromo-5-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-7-carbaldehyde → HCID 57546143, compound

HRID 913875Notes

Reaction equation

HRID 913875 reaction equation
[Br:1][C:2]1[C:10]2[C:5](=[C:6]([CH:12]=[O:13])[CH:7]=[C:8]([Cl:11])[CH:9]=2)[N:4]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])[N:3]=1.[CH3:22][Mg]Br>O1CCCC1>[Br:1][C:2]1[C:10]2[C:5](=[C:6]([CH:12]([OH:13])[CH3:22])[CH:7]=[C:8]([Cl:11])[CH:9]=2)[N:4]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])[N:3]=1

Participants

4

Reactant 2

HCID 575461403-Bromo-5-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-7-carbaldehydeHCID 178418573HCID 178418573, compound

Product 1

HCID 57546143HCID 57546143, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

3-Bromo-5-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-7-carbaldehyde (1.35 g, 3.46 mmol) was dissolved in tetrahydrofuran (10 mL), cooled to −78° C. and treated with methylmagnesium bromide (3.0 M in diethyl ether, 1.7 mL, 5.20 mmol) over several minutes. After 1 h, the ice bath was removed and stirring continued for 1 h at room temperature. The reaction was cooled to 0° C., treated with saturated ammonium chloride and diluted with ethyl acetate. The layers were separated. The organic layer was washed with water (2×), brine (2×), dried over sodium sulfate, filtered and concentrated. Flash chromatography on silica gel (30% ethyl acetate/hexanes) afforded 1.29 g (92%) as a brown oil. 1H-NMR (CDCl3, 300 MHz) δ 7.51-7.53 (m, 2H), 5.91 (qAB, JAB=11.7 Hz, 2H), 5.52-5.54 (m, 1H), 3.49-3.54 (m, 2H), 1.63 (d, J=6.6 Hz, 3H), 0.78-0.83 (m, 2H), 0.09 (s, 9H). Mass spec.: 429.18 (MNa)+.

Workup

  1. customthe ice bath was removed
  2. waitcontinued for 1 h at room temperature
  3. temperatureThe reaction was cooled to 0° C.
  4. additiontreated with saturated ammonium chloride
  5. additiondiluted with ethyl acetate
  6. customThe layers were separated
  7. washThe organic layer was washed with water (2×), brine (2×)
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customFlash chromatography on silica gel (30% ethyl acetate/hexanes) afforded 1.29 g (92%) as a brown oil

Sources & evidence

ORD record
ord-b20c2224be7c437b92f0b8fc4b84dd61
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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