2-Chloro-N-methoxy-N-methylacetamide → 2-chloro-1-(1-[2-(trimethylsilyl)ethoxy]methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)ethanone

HRID 1501386Notes

Reaction equation

HRID 1501386 reaction equation
Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[CH:9]=[CH:10][C:3]=12.C([Mg]Cl)(C)C.[Cl:24][CH2:25][C:26](N(OC)C)=[O:27]>CCOCC.C1COCC1>[Cl:24][CH2:25][C:26]([C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[CH:9]=[CH:10][C:3]=12)=[O:27]

Participants

6

Reactant 3

HCID 27347162-Chloro-N-methoxy-N-methylacetamideHCID 574775614-bromo-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridineHCID 178418918HCID 178418918, compound

Product 1

HCID 574775702-chloro-1-(1-[2-(trimethylsilyl)ethoxy]methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)ethanoneYield 35%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 4-bromo-1-[2-(trimethylsilyl)ethoxy]methyl-1H-pyrrolo[2,3-b]pyridine (2.05 g, 0.00626 mol) in THF (10 mL, 0.123 mol) at 0° C. was added dropwise a solution of isopropylmagnesium chloride in ether (2.0 M, 9.4 mL). The mixture was allowed to warm to room temperature and stirred for 4 hours. This mixture was then transferred via cannula to a solution of 2-chloro-N-methoxy-N-methylacetamide (2.84 g, 0.0207 mol) in THF (10 ml). After 30 minutes reaction time, the solution was quenched by the addition of saturated ammonium chloride aqueous solution. The product was extracted with ethyl acetate, the combined organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The crude residue was purified by flash column chromatography (0-20% ethyl acetate/hexanes) to afford 2-chloro-1-(1-[2-(trimethylsilyl)-ethoxy]methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)ethanone (711 mg, 35%). 1H NMR (400 MHz, CDCl3): δ 8.56 (d, 1H), 7.66 (d, 1H), 7.60 (d, 1H), 7.23 (d, 1H), 5.80 (s, 2H), 4.91 (s, 2H), 3.60 (dd, 2H), 0.98 (dd, 2H), 0.01 (s, 9H); MS (ES): 325 (M+1).

Workup

  1. customAfter 30 minutes reaction time
  2. customthe solution was quenched by the addition of saturated ammonium chloride aqueous solution
  3. extractionThe product was extracted with ethyl acetate
  4. washthe combined organic extracts were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude residue was purified by flash column chromatography (0-20% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-98b850727daf4f598337b4f772b144d6
Source dataset
uspto-grants-2015_12
Patent number
US09206187B2

Reaction notes

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