Methanol → 1-(6-Methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)ethanone

HRID 1527250Notes

Reaction equation

HRID 1527250 reaction equation
[Al+3].[Cl-].[Cl-].[Cl-].[CH3:5][O:6][C:7]1[N:15]=[C:14]2[C:10]([CH:11]=[CH:12][NH:13]2)=[CH:9][CH:8]=1.[C:16](Cl)(=[O:18])[CH3:17].CO>C(Cl)Cl>[CH3:5][O:6][C:7]1[N:15]=[C:14]2[NH:13][CH:12]=[C:11]([C:16](=[O:18])[CH3:17])[C:10]2=[CH:9][CH:8]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 6367Acetyl chlorideHCID 6451240Aluminum(III) ChlorideHCID 116151916-Methoxy-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 682845331-(6-Methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)ethanone

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of AlCl3 (1.37 g, 10.3 mmol) in CH2Cl2 (40 mL) was added 6-methoxy-7-azaindole (315 mg, 2.07 mmol) and the mixture was stirred at RT for 30 min under nitrogen. Acetyl chloride (736 μL, 10.3 mmol) was added dropwise and the resulting mixture stirred at RT overnight. MeOH (8 mL) was added cautiously to quench the reaction and the solvents were removed under vacuum. The residue was purified by flash column chromatography on silica gel (CH2Cl2 to CH2Cl2/MeOH 93-7) and by preparative HPLC (Waters Sunfire C18-ODB, 5 μm, 30×100 mm, 5% to 100% CH3CN in H2O in 25 min, CH3CN and H2O containing 0.1% TFA, flow: 40 mL/min) to give after neutralization (aqueous saturated NaHCO3) and extraction (CH2Cl2) of the purified fractions the desired compound TLC, Rf (CH2Cl2/MeOH 9:1)=0.55; MS (UPLC/MS): 191.2 [M+H]+, 189.1 [M−H]−, 379.2 [2M−H]−; tR (HPLC conditions f): 1.45 min. 1H-NMR (400 MHz, DMSO): δ (ppm): 8.35 (d, 1H), 8.29 (s, 1H), 6.75 (d, 1H), 5.04 (s, 2H), 3.89 (s, 3H), 2.44 (s, 3H).

Workup

  1. stirringthe resulting mixture stirred at RT overnight
  2. customto quench
  3. customthe reaction
  4. customthe solvents were removed under vacuum
  5. customThe residue was purified by flash column chromatography on silica gel (CH2Cl2 to CH2Cl2/MeOH 93-7) and by preparative HPLC (Waters Sunfire C18-ODB, 5 μm, 30×100 mm, 5% to 100% CH3CN in H2O in 25 min, CH3CN and H2O containing 0.1% TFA, flow: 40 mL/min)
  6. customto give
  7. extractionafter neutralization (aqueous saturated NaHCO3) and extraction (CH2Cl2) of the
  8. custompurified fractions the desired compound TLC, Rf (CH2Cl2/MeOH 9:1)=0.55
  9. custom1.45 min

Sources & evidence

ORD record
ord-8ec112497a1e4ba7856e5bfe8845140e
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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