Sodium hydride → HCID 57581128, compound

HRID 1982943Notes

Reaction equation

HRID 1982943 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[NH:15][C:14]4[CH:16]=[CH:17][CH:18]=[C:19]([CH2:20][O:21][CH3:22])[C:13]=4[N:12]=3)=[N:9][NH:8][C:5]2=[N:6][CH:7]=1.[H-].[Na+].[CH3:25][Si:26]([CH2:29][CH2:30][O:31][CH2:32]Cl)([CH3:28])[CH3:27]>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:15]([CH2:32][O:31][CH2:30][CH2:29][Si:26]([CH3:28])([CH3:27])[CH3:25])[C:14]4[CH:16]=[CH:17][CH:18]=[C:19]([CH2:20][O:21][CH3:22])[C:13]=4[N:12]=3)=[N:9][N:8]([CH2:32][O:31][CH2:30][CH2:29][Si:26]([CH3:28])([CH3:27])[CH3:25])[C:5]2=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 178494486HCID 178494486, compound

Product 1

HCID 57581128HCID 57581128, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

5-bromo-3-(4-methoxymethyl-1H-benzoimidazol-2-yl)-1H-pyrazolo[3,4-b]pyridine Compound 11 (1.2 g, 4.19 mmol) was dissolved in dry THF (20 mL). The solution was cooled to 0° C. before sodium hydride (0.37 g, 60% in mineral oil, 9.25 mmol) was added in portions. The suspension was stirred at 0° C. for additional 15 minutes before (trimethylsilyl)ethoxymethyl chloride (1.78 mL, 10.06 mmol) was added. The reaction was warmed to room temperature and stirred overnight. Solvent was removed and the residue was purified by silica gel chromatography (10% to 50% ethyl acetate in hexanes) to yield 5-bromo-3-[4-methoxymethyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-2-yl]-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridine Compound 12a (1.59 g, 77%) as amber oil. 1H NMR (300 MHz, CDCl3) δ 9.35 (d, 1H, J=2.4 Hz), 8.84 (d, 1H, J=2.4 Hz), 7.74 (d, 1H, J=5.4 Hz), 7.57 (m, 2H), 6.45 (s, 2H), 6.09 (s, 2H), 5.26 (s, 2H), 3.86 (m, 4H), 3.77 (s, 3H), 1.13 (t, 2H, J=7.2 Hz), 1.05 (t, 2H, J=7.8 Hz), 0.14 (s, 9H), 0.03 (s, 9H); MS (ESI) m/z: 619 (M+H+).

Workup

  1. additionwas added in portions
  2. additionwas added
  3. customSolvent was removed
  4. customthe residue was purified by silica gel chromatography (10% to 50% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-0e4da4ec60af42ffbea28a64659fb435
Source dataset
uspto-grants-2009_06
Patent number
US07541367B2

Reaction notes

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