(3R)-3-Aminopiperidine, 3-BOC protected → HCID 67045323, compound

HRID 1923766Notes

Reaction equation

HRID 1923766 reaction equation
[Br:1][C:2]1[C:3](F)=[C:4]2[C:10]([NH:11][C:12]([C:14]3([C:17]([F:20])([F:19])[F:18])[CH2:16][CH2:15]3)=[O:13])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[NH:22]1[CH2:27][CH2:26][CH2:25][C@@H:24]([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:23]1>CCCCO>[Br:1][C:2]1[C:3]([N:22]2[CH2:27][CH2:26][CH2:25][C@@H:24]([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:33])([CH3:32])[CH3:34])[CH2:23]2)=[C:4]2[C:10]([NH:11][C:12]([C:14]3([C:17]([F:20])([F:19])[F:18])[CH2:16][CH2:15]3)=[O:13])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1

Participants

4

Reactant 2

HCID 1514172(3R)-3-Aminopiperidine, 3-BOC protectedHCID 60205386HCID 60205386, compound

Product 1

HCID 67045323HCID 67045323, compoundYield 19%

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)-1-(trifluoromethyl)cyclopropanecarboxamide (229 mg, 0.627 mmol) in n-BuOH (5 mL) was treated with (R)-tert-butyl piperidin-3-ylcarbamate (505 mg, 2.507 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. The residue was 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-(1-(trifluoromethyl)cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (65 mg, 19% yield) as a solid. LCMS (APCI+) m/z 429.1, 446.1, 492.1, 548.1 (M+H)+, Retention time=3.79 minutes (Method 3).

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. customThe residue was purified by C-18 reverse phase flash chromatography (Biotage SP4 unit

Sources & evidence

ORD record
ord-a036a5ae3ae541a4b6445947621b03b0
Source dataset
uspto-grants-2012_05
Patent number
US08178131B2

Reaction notes

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