Tert-butyl (3-methylpiperidin-3-yl)carbamate → N-(4-(3-Amino-3-methylpiperidin-1-yl)-5-bromo-1H-pyrrolo [2,3-b]pyridin-3-yl)-2-methoxyacetamide

HRID 408230Notes

Reaction equation

HRID 408230 reaction equation
[Br:1][C:2]1[C:3](F)=[C:4]2[C:10]([NH:11][C:12](=[O:16])[CH2:13][O:14][CH3:15])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[CH3:18][C:19]1([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])[CH2:24][CH2:23][CH2:22][NH:21][CH2:20]1>CCCCO>[NH2:25][C:19]1([CH3:18])[CH2:24][CH2:23][CH2:22][N:21]([C:3]2[C:2]([Br:1])=[CH:7][N:6]=[C:5]3[NH:8][CH:9]=[C:10]([NH:11][C:12](=[O:16])[CH2:13][O:14][CH3:15])[C:4]=23)[CH2:20]1.[Br:1][C:2]1[C:3]([N:21]2[CH2:22][CH2:23][CH2:24][C:19]([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:18])[CH2:20]2)=[C:4]2[C:10]([NH:11][C:12](=[O:16])[CH2:13][O:14][CH3:15])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1

Participants

5

Reactant 2

HCID 19691473Tert-butyl (3-methylpiperidin-3-yl)carbamateHCID 60205365N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-methoxyacetamide

Product 2

HCID 58195557N-(4-(3-Amino-3-methylpiperidin-1-yl)-5-bromo-1H-pyrrolo [2,3-b]pyridin-3-yl)-2-methoxyacetamideYield 49%HCID 60205373tert-butyl 1-(5-bromo-3-(2-methoxyacetamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)-3-methylpiperidin-3-ylcarbamateYield 19%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

N-(5-Bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-methoxyacetamide (100 mg, 0.331 mmol, Example 31, Step A) and tert-butyl 3-methylpiperidin-3-ylcarbamate (213 mg, 0.993 mmol) in n-BuOH (4 mL) were heated to 160° C. for 48 hours in a sealed tube. After concentration, the residue was purified by C-18 reverse phase flash chromatography (Biotage SP4 unit, C-18 25M column, 10-90% CH3CN/water gradient; 30 CV) to yield N-(4-(3-amino-3-methylpiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-methoxyacetamide (65 mg, 49% yield) as a solid and tert-butyl 1-(5-bromo-3-(2-methoxyacetamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)-3-methylpiperidin-3-ylcarbamate (32 mg, 19% yield) as an oil.

Workup

  1. concentrationAfter concentration
  2. customthe residue was purified by C-18 reverse phase flash chromatography (Biotage SP4 unit

Sources & evidence

ORD record
ord-a11350c4f70f4b6da1d1997975829b2c
Source dataset
uspto-grants-2014_06
Patent number
US08758830B2

Reaction notes

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