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

HRID 1521723Notes

Reaction equation

HRID 1521723 reaction equation
[H-].[Na+].[NH:3]1[C:7]2=[N:8][C:9]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:10][CH:11]=[C:6]2[CH:5]=[C:4]1[C:17]([O:19][CH2:20][CH3:21])=[O:18].[CH3:22][C@@H:23]1OS(=O)(=O)[N:25]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:24]1>CN(C=O)C>[C:33]([O:32][C:30]([NH:25][CH2:24][C@@H:23]([N:3]1[C:7]2=[N:8][C:9]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:10][CH:11]=[C:6]2[CH:5]=[C:4]1[C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH3:22])=[O:31])([CH3:36])([CH3:35])[CH3:34]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 11195739(s)-Tert-butyl 5-methyl-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxideHCID 67236396Diethyl 1H-pyrrolo[2,3-B]pyridine-2,6-dicarboxylate2×

Product 1

HCID 67238103Diethyl (S)-1-(1-((tert-butoxycarbonyl)amino)propan-2-yl)-1H-pyrrolo[2,3-b]pyridine-2,6-dicarboxylateYield 63%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
0 °C

Procedure

To a suspension of 60% sodium hydride in mineral oil (503 mg, 12.6 mmol) in DMF (10 mL) cooled to 0° C. is added a solution of diethyl 1H-pyrrolo[2,3-b]pyridine-2,6-dicarboxylate (Intermediate D, 3.00 g, 11.4 mmol) in DMF (10 mL), dropwise. The mixture is stirred at 0° C. for 30 min after which a solution of tert-butyl (5S)-5-methyl-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide (2.71 g, 11.4 mmol) in DMF (10 mL) is added. The mixture is allowed to warm and stir at room temperature for 16 h. The reaction is quenched with H2O and is 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 0-30% ethyl acetate/heptane to afford the title compound (3.00 g, 63%). LCMS: 442.86 (M+Na+).

Workup

  1. additionis added
  2. temperatureto warm
  3. customThe reaction is quenched with H2O
  4. stirringis stirred for 15 min
  5. extractionThe mixture is extracted with ethyl acetate
  6. washthe combined organic phases are washed with brine
  7. dry with materialare dried (Na2SO4)
  8. customThe solvent is removed in vacuo
  9. customthe crude material is purified via flash column chromatography
  10. washa gradient elution of 0-30% ethyl acetate/heptane

Sources & evidence

ORD record
ord-9707583393d34f6fa38b2af6aea0d0ff
Source dataset
uspto-grants-2015_07
Patent number
US09073926B2

Reaction notes

Loading…