(+-)-2-Butanol → Tert-butyl (1r)-3-(5-bromo-3-(2,2-dimethylcyclopropanecarboxamido)-1h-pyrrolo[2,3-b]pyridin-4-yl)cyclohexylcarbamate

HRID 875929Notes

Reaction equation

HRID 875929 reaction equation
[Br:1][C:2]1[C:3](F)=[C:4]2[C:10]([NH:11][C:12]([CH:14]3[CH2:16][C:15]3([CH3:18])[CH3:17])=[O:13])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.N1[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]1.[CH:34](O)(CC)C>>[Br:1][C:2]1[C:3]([CH:34]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]([CH:14]3[CH2:16][C:15]3([CH3:18])[CH3:17])=[O:13])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1

Participants

4

Reactant 3

HCID 6568(+-)-2-ButanolHCID 1514172(3R)-3-Aminopiperidine, 3-BOC protectedHCID 60205714N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2,2-dimethylcyclopropanecarboxamide

Product 1

HCID 60205715Tert-butyl (1r)-3-(5-bromo-3-(2,2-dimethylcyclopropanecarboxamido)-1h-pyrrolo[2,3-b]pyridin-4-yl)cyclohexylcarbamateYield 46.5%

Procedure

N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2,2-dimethylcyclopropanecarboxamide (500 mg, 1.53 mmol) and (R)-tert-butyl piperidin-3-ylcarbamate (921 mg, 4.60 mmol) in s-BuOH (10 mL) were stirred at 130° C. for 18 hours. The reaction was concentrated and purified by reverse phase chromatography (SP4, 25M, water/ACN 90/10→0/100, 30 CV) to yield tert-butyl (1R)-3-(5-bromo-3-(2,2-dimethylcyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)cyclohexylcarbamate (360 mg, 46.5% yield) as a solid.

Workup

  1. concentrationThe reaction was concentrated
  2. custompurified by reverse phase chromatography (SP4, 25M, water/ACN 90/10→0/100, 30 CV)

Sources & evidence

ORD record
ord-cc613837d0434538b8af9efc616c53d3
Source dataset
uspto-grants-2015_03
Patent number
US08981085B2

Reaction notes

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