Sodium hydride → 4-Bromo-5-methoxy-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-c]pyridine

HRID 1909070Notes

Reaction equation

HRID 1909070 reaction equation
[H-].[Na+].[Br:3][C:4]1[C:9]([O:10][CH3:11])=[N:8][CH:7]=[C:6]2[NH:12][CH:13]=[CH:14][C:5]=12.Cl[CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21]>C1COCC1>[Br:3][C:4]1[C:9]([O:10][CH3:11])=[N:8][CH:7]=[C:6]2[N:12]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[CH:13]=[CH:14][C:5]=12

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 665998491H-Pyrrolo[2,3-c]pyridine, 4-broMo-5-Methoxy-

Product 1

HCID 665997094-Bromo-5-methoxy-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-c]pyridine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
23 °C

Procedure

To a suspension of NaH (0.238 g, 5.95 mmol, 1.3 eq, 60%) in THF at 0° C. was added a solution of 4-Bromo-5-methoxy-1H-pyrrolo[2,3-c]pyridine (1.05 g, 4.62 mmol) in THF and the solution stirred until no effervescence was observed (approx. 5 minutes). To the reaction mixture was added (2-Chloromethoxy-ethyl)-trimethyl-silane (1.00 mL, 5.64 mmol, 1.2 eq) and the solution was warmed to 23° C. and stirred for 16 hr. The reaction was quenched using sat'd NaHCO3 (aq) and most of the THF removed under reduced pressure. The aqueous layer was partitioned between EtOAc (100 mL), the organic layer washed with water, brine, dried, and concentrated. The crude reaction was purified using chromatography eluting with 20% EtOAc/Heptane giving 4-Bromo-5-methoxy-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-c]pyridine beige crystalline product (0.950 g, 2.53 mmol, 55%). MS ESI m/z 359.2 (M+2H)+. 1NMR (400 MHz, CDCl3) δ 8.46 (d, J=0.6 Hz 1H), 8.36 (s, 1H), 7.39 (d, J=3.2 Hz, 1H), 6.54 (dd, J=3.2 Hz, 0.6 Hz, 1H), 5.51 (s, 2H), 4.14 (s, 3H), 3.51 (m, 2H), 0.94 (m, 2H), 0.00 (s, 9H).

Workup

  1. custom(approx. 5 minutes)
  2. stirringstirred for 16 hr
  3. customThe reaction was quenched
  4. custommost of the THF removed under reduced pressure
  5. customThe aqueous layer was partitioned between EtOAc (100 mL)
  6. washthe organic layer washed with water, brine
  7. customdried
  8. concentrationconcentrated
  9. customThe crude reaction
  10. customwas purified
  11. washeluting with 20% EtOAc/Heptane

Sources & evidence

ORD record
ord-6cf5e2837d3a4b5ca82d74c3a7d68058
Source dataset
uspto-grants-2013_12
Patent number
US08598217B2

Reaction notes

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