Dimethyl Disulfide → (R)-tert-butyl 1-(5-(methylthio)-3-(nicotinamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate

HRID 875829

Reaction equation

HRID 875829 reaction equation
Br[C:2]1[C:3]([N:20]2[CH2:25][CH2:24][CH2:23][C@@H:22]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[CH2:21]2)=[C:4]2[C:10]([NH:11][C:12](=[O:19])[C:13]3[CH:18]=[CH:17][CH:16]=[N:15][CH:14]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[Li]C.C([Li])CCC.[CH3:41][S:42]SC>C1COCC1>[CH3:41][S:42][C:2]1[C:3]([N:20]2[CH2:25][CH2:24][CH2:23][C@@H:22]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[CH2:21]2)=[C:4]2[C:10]([NH:11][C:12](=[O:19])[C:13]3[CH:18]=[CH:17][CH:16]=[N:15][CH:14]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 12232Dimethyl DisulfideHCID 67045441(R)-tert-butyl 1-(5-bromo-3-(nicotinamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamateHCID 178418339ButyllithiumHCID 178418348HCID 178418348, compound

Product 1

HCID 67045567(R)-tert-butyl 1-(5-(methylthio)-3-(nicotinamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamateYield 50%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

(R)-tert-Butyl 1-(5-bromo-3-(nicotinamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (150 mg, 0.291 mmol; Example 1A, Step A) was dissolved in THF (20 mL) and cooled to −78° C. MeLi (546 μL, 0.873 mmol) was then added slowly, and the reaction was stirred for 10 minutes. n-Butyl lithium (128 μL, 0.320 mmol) was added next, and the reaction was stirred for an additional 10 minutes, followed by the addition of 1,2-dimethyldisulfane (31.5 mg, 0.335 mmol). The reaction was stirred for 30 minutes and then quenched with water. The reaction was extracted several times with DCM. The organic layer was dried, filtered, and concentrated. The resulting residue was purified by reverse phase chromatography (Biotage Horizon, C-18 25M+, 10-85% CH3CN/water) to provide 50% pure (R)-tert-butyl 1-(5-(methylthio)-3-(nicotinamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate, which was used without further purification.

Workup

  1. stirringthe reaction was stirred for an additional 10 minutes
  2. stirringThe reaction was stirred for 30 minutes
  3. customquenched with water
  4. extractionThe reaction was extracted several times with DCM
  5. customThe organic layer was dried
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting residue was purified by reverse phase chromatography (Biotage Horizon

Sources & evidence

ORD record
ord-916fc198f14c49e69c88bc275686eaa6
Source dataset
uspto-grants-2015_03
Patent number
US08981085B2

Linked notes

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