Sodium hydride → methyl [1-((2R)-4-{[tert-butyl(dimethyl)silyl]oxy}-2-{[(4-fluorophenyl)sulfonyl]amino}butyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]acetate

HRID 1036630Notes

Reaction equation

HRID 1036630 reaction equation
[NH:1]1[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[C:3]([CH2:10][C:11]([O:13][CH3:14])=[O:12])=[CH:2]1.[H-].[Na+].[Si:17]([O:24][CH2:25][CH2:26][C@@H:27]1[CH2:29][N:28]1[S:30]([C:33]1[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=1)(=[O:32])=[O:31])([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18].[Cl-].[NH4+]>CN(C=O)C.C(OCC)(=O)C>[CH3:14][O:13][C:11](=[O:12])[CH2:10][C:3]1[C:4]2[C:5](=[N:6][CH:7]=[CH:8][CH:9]=2)[N:1]([CH2:29][C@H:27]([NH:28][S:30]([C:33]2[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=2)(=[O:32])=[O:31])[CH2:26][CH2:25][O:24][Si:17]([C:20]([CH3:23])([CH3:21])[CH3:22])([CH3:18])[CH3:19])[CH:2]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 25067325Methyl 2-(1H-pyrrolo[2,3-b]pyridin-3-yl)acetateHCID 58399169(2R)-2-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-1-[(4-fluoro-phenyl)sulfonyl]aziridine

Product 1

HCID 86655913methyl [1-((2R)-4-{[tert-butyl(dimethyl)silyl]oxy}-2-{[(4-fluorophenyl)sulfonyl]amino}butyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]acetateYield 37.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a cooled solution at 0° C. of methyl 1H-pyrrolo[2,3-b]pyridin-3-ylacetate (1.1 g, 5.8 mmol) in DMF (12 mL) was added 60% NaH in oil (0.26 g, 6.4 mmol, 1.1 equiv.). After a period of 10 min at room temperature, the reaction mixture was cooled to 0° C. and a DMF solution (12 mL) of (2R)-2-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-1-[(4-fluorophenyl)-sulfonyl]aziridine (2.0 g, 5.8 mmol) was added. The reaction was aged 0.5 h at room temperature and poured over saturated ammonium chloride and ethyl acetate. The organic phase was separated, dried over sodium sulfate, filtered and evaporated under reduced pressure. The residue was purified by combiflash (hexane to 50% ethyl acetate in hexane) to provide 1.2 g of the title compound.

Workup

  1. waitThe reaction was aged 0.5 h at room temperature
  2. customThe organic phase was separated
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated under reduced pressure
  6. customThe residue was purified by combiflash (hexane to 50% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-a603c40d6dda47a2ac6a9d622813d31b
Source dataset
uspto-grants-2013_10
Patent number
US08546422B2

Reaction notes

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