Sodium hydride → 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(2-methoxy-ethoxy)-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid ethyl ester

HRID 2250439Notes

Reaction equation

HRID 2250439 reaction equation
[H-].[Na+].[CH2:3]([O:5][C:6]([C:8]1[NH:21][C:11]2=[CH:12][N:13]=[C:14]([O:16][CH2:17][CH2:18][O:19][CH3:20])[CH:15]=[C:10]2[CH:9]=1)=[O:7])[CH3:4].Br[CH2:23][C:24]1[CH:28]=[C:27]([C:29]2[S:30][C:31]([Cl:34])=[CH:32][CH:33]=2)[O:26][N:25]=1>CN(C=O)C>[CH2:3]([O:5][C:6]([C:8]1[N:21]([CH2:23][C:24]2[CH:28]=[C:27]([C:29]3[S:30][C:31]([Cl:34])=[CH:32][CH:33]=3)[O:26][N:25]=2)[C:11]2=[CH:12][N:13]=[C:14]([O:16][CH2:17][CH2:18][O:19][CH3:20])[CH:15]=[C:10]2[CH:9]=1)=[O:7])[CH3:4]

Participants

5

Reactant 3

HCID 24758Sodium hydride2×HCID 111501463-Bromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazole2×HCID 59820057ethyl 5-(2-methoxyethoxy)-1H-pyrrolo[2,3-c]pyridine-2-carboxylate

Product 1

HCID 692251001-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(2-methoxy-ethoxy)-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

105 mg (4.16 mmol) NaH (96%) were added to a solution of 5-(2-Methoxy-ethoxy)-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid ethyl ester in 50 mL absolute DMF and the mixture was stirred for 30 min. at room temperature. 1.05 g (3.78 mmol) 3-Bromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazole were added and the the mixture and stirring was continued for 3 h. After addition of 21 mg (0.832 mmol) NaH (96%) and 210 mg (0.756 mmol) 3-Bromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazole and standing overnight the mixture was concentrated in vacuo. The residue was dissolved in CH2Cl2 and the solution washed with saturated NaHCO3 solution. The solvent was removed in vacuo and the residue purified by flash chromatography over silica gel using n-heptane/ethyl acetate=3/2 as solvent. The fractions containing the product were concentrated.

Workup

  1. stirringthe the mixture and stirring
  2. waitwas continued for 3 h
  3. waitstanding overnight
  4. concentrationthe mixture was concentrated in vacuo
  5. dissolutionThe residue was dissolved in CH2Cl2
  6. washthe solution washed with saturated NaHCO3 solution
  7. customThe solvent was removed in vacuo
  8. customthe residue purified by flash chromatography over silica gel
  9. additionThe fractions containing the product
  10. concentrationwere concentrated

Sources & evidence

ORD record
ord-528824721d08480b8cf310cad7cef027
Source dataset
uspto-grants-2008_01
Patent number
US07317027B2

Reaction notes

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