(3R)-3-Aminopiperidine, 3-BOC protected → (R)-tert-butyl 1-(5-bromo-3-(6-methoxypicolinamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate

HRID 1923760Notes

Reaction equation

HRID 1923760 reaction equation
[Br:1][C:2]1[C:3](F)=[C:4]2[C:10]([NH:11][C:12](=[O:21])[C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[N:14]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[NH:23]1[CH2:28][CH2:27][CH2:26][C@@H:25]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[CH2:24]1>CCCCO>[Br:1][C:2]1[C:3]([N:23]2[CH2:28][CH2:27][CH2:26][C@@H:25]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:34])([CH3:33])[CH3:35])[CH2:24]2)=[C:4]2[C:10]([NH:11][C:12](=[O:21])[C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[N:14]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1

Participants

4

Reactant 2

HCID 1514172(3R)-3-Aminopiperidine, 3-BOC protectedHCID 60205376N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-6-methoxypicolinamide

Product 1

HCID 67045126(R)-tert-butyl 1-(5-bromo-3-(6-methoxypicolinamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamateYield 27%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
160 °C

Procedure

A solution of N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-6-methoxypicolinamide (228 mg, 0.624 mmol) in n-BuOH (5 mL) was treated with (R)-tert-butyl piperidin-3-ylcarbamate (375 mg, 1.87 mmol) and stirred at 160° C. for 48 hours in a sealed tube. The mixture was concentrated in vacuo, and the residue diluted with water (25 mL) and extracted with EtOAc (3×20 mL). The combined organic extracts were dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated in vacuo and purified by C-18 reverse phase flash chromatography (Biotage SP4 unit, C-18 25M column, 5-85% CH3CN/water gradient; 25 CV) to provide (R)-tert-butyl 1-(5-bromo-3-(6-methoxypicolinamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (91.5 mg, 27% yield) as a solid. LCMS (APCI+) m/z 445.1, 447.1, 454.1 (M+H)+, Retention time=4.03 minutes (Method 2).

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. additionthe residue diluted with water (25 mL)
  3. extractionextracted with EtOAc (3×20 mL)
  4. dry with materialThe combined organic extracts were dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo
  7. custompurified by C-18 reverse phase flash chromatography (Biotage SP4 unit

Sources & evidence

ORD record
ord-19f3564b04874d3c908cb0a38123b78e
Source dataset
uspto-grants-2012_05
Patent number
US08178131B2

Reaction notes

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