Sodium hydride → Diethyl 1-{3-[(tert-butoxycarbonyl)amino]butan-2-yl}-1H-pyrrolo[2,3-b]pyridine-2,6-dicarboxylate

HRID 1521713Notes

Reaction equation

HRID 1521713 reaction equation
[NH:1]1[C:5]2=[N:6][C:7]([C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:8][CH:9]=[C:4]2[CH:3]=[C:2]1[C:15]([O:17][CH2:18][CH3:19])=[O:16].[H-].[Na+].[CH3:22][CH:23]1[CH:27]([CH3:28])OS(=O)(=O)[N:24]1[C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32]>CN(C=O)C>[C:34]([O:33][C:31]([NH:24][CH:23]([CH3:22])[CH:27]([N:1]1[C:5]2=[N:6][C:7]([C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:8][CH:9]=[C:4]2[CH:3]=[C:2]1[C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH3:28])=[O:32])([CH3:37])([CH3:36])[CH3:35]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 67236396Diethyl 1H-pyrrolo[2,3-B]pyridine-2,6-dicarboxylate2×HCID 86682386Tert-butyl 4,5-dimethyl-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide

Product 1

HCID 67236832Diethyl 1-{3-[(tert-butoxycarbonyl)amino]butan-2-yl}-1H-pyrrolo[2,3-b]pyridine-2,6-dicarboxylateYield 106.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of diethyl 1H-pyrrolo[2,3-b]pyridine-2,6-dicarboxylate (Intermediate D, 3.40 g, 13.0 mmol) in DMF (15 mL) cooled to 0° C. is added 60% sodium hydride in mineral oil (570 mg, 14.3 mmol). The mixture is stirred at 0° C. for 20 min after which a solution of tert-butyl 4,5-dimethyl-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide (5.35 g, 14.3 mmol) in DMF (10 mL) is added. The mixture is stirred at 0° C. for 30 min after which the reaction was allowed to warm and stir at ambient temperature overnight. The reaction is quenched with H2O and was stirred for 15 min. The mixture is extracted with ethyl acetate and the combined organic phases are washed with brine, and are dried (Na2SO4). The solvent is removed in vacuo and the crude material is purified via flash column chromatography using a gradient elution of 0-20% ethyl acetate/heptane to afford the title compound as a colorless oil (6.00 g, quantitative). LCMS: 434.83 (M+H+).

Workup

  1. additionis added
  2. temperatureto warm
  3. stirringstir at ambient temperature overnight
  4. customThe reaction is quenched with H2O
  5. stirringwas stirred for 15 min
  6. extractionThe mixture is extracted with ethyl acetate
  7. washthe combined organic phases are washed with brine
  8. dry with materialare dried (Na2SO4)
  9. customThe solvent is removed in vacuo
  10. customthe crude material is purified via flash column chromatography
  11. washa gradient elution of 0-20% ethyl acetate/heptane

Sources & evidence

ORD record
ord-fc9df301e56c486fa90dec2fbe8be2ff
Source dataset
uspto-grants-2015_07
Patent number
US09073926B2

Reaction notes

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