(3R)-3-Aminopiperidine, 3-BOC protected → (R)-tert-Butyl 1-(5-chloro-3-(cyclopentanecarboxamido)-1H-pyrrolo [2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate

HRID 1034909Notes

Reaction equation

HRID 1034909 reaction equation
[NH:1]1[CH2:6][CH2:5][CH2:4][C@@H:3]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11])[CH2:2]1.[Cl:15][C:16]1[C:17](F)=[C:18]2[C:24]([NH:25][C:26]([CH:28]3[CH2:32][CH2:31][CH2:30][CH2:29]3)=[O:27])=[CH:23][NH:22][C:19]2=[N:20][CH:21]=1>C(O)(CC)C>[Cl:15][C:16]1[C:17]([N:1]2[CH2:6][CH2:5][CH2:4][C@@H:3]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:11])([CH3:13])[CH3:12])[CH2:2]2)=[C:18]2[C:24]([NH:25][C:26]([CH:28]3[CH2:29][CH2:30][CH2:31][CH2:32]3)=[O:27])=[CH:23][NH:22][C:19]2=[N:20][CH:21]=1

Participants

4

Reactant 2

HCID 1514172(3R)-3-Aminopiperidine, 3-BOC protectedHCID 60205684N-(5-chloro-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)cyclopentanecarboxamide

Product 1

HCID 67045325(R)-tert-Butyl 1-(5-chloro-3-(cyclopentanecarboxamido)-1H-pyrrolo [2,3-b]pyridin-4-yl)piperidin-3-ylcarbamateYield 58%

Reagents, catalysts & solvents 1

HCID 6568(+-)-2-ButanolSolvent

Conditions

Temperature
130 °C

Procedure

(R)-tert-Butyl piperidin-3-ylcarbamate (192 mg, 0.96 mmol) was added to N-(5-chloro-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)cyclopentanecarboxamide (90 mg, 0.32 mmol) in s-BuOH (2 mL), and the reaction mixture was heated to 130° C. for 30 hours in a sealed tube. After cooling down, the reaction was concentrated to dryness, dissolved in AcOEt (10 mL) and washed with 10% aqueous citric acid and brine. The aqueous phase was diluted with hexanes (10 mL) and passed through a short plug of silica gel. The silica gel was rinsed with AcOEt/hexanes (1/1, 100 mL), and the combined organic phases were concentrated in vacuo. The resulting solid was crystallized from AcOEt to yield (R)-tert-butyl 1-(5-chloro-3-(cyclopentanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (85 mg, 58% yield) as a solid.

Workup

  1. temperatureAfter cooling down
  2. concentrationthe reaction was concentrated to dryness
  3. dissolutiondissolved in AcOEt (10 mL)
  4. washwashed with 10% aqueous citric acid and brine
  5. additionThe aqueous phase was diluted with hexanes (10 mL)
  6. washThe silica gel was rinsed with AcOEt/hexanes (1/1, 100 mL)
  7. concentrationthe combined organic phases were concentrated in vacuo
  8. customThe resulting solid was crystallized from AcOEt

Sources & evidence

ORD record
ord-3abf8142990a414290fa466eba973c00
Source dataset
uspto-grants-2013_10
Patent number
US08545897B2

Reaction notes

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