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

HRID 875748Notes

Reaction equation

Cl[C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=[C:4]2[NH:12][CH:13]=[C:14]([NH:15][C:16]([C:18]3[CH:23]=[N:22][CH:21]=[CH:20][N:19]=3)=[O:17])[C:3]=12.[NH:24]1[CH2:29][CH2:28][CH2:27][C@@H:26]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[CH2:25]1>CCCCO>[N:19]1[CH:20]=[CH:21][N:22]=[CH:23][C:18]=1[C:16]([NH:15][C:14]1[C:3]2[C:4](=[N:5][CH:6]=[C:7]([C:8]([F:11])([F:10])[F:9])[C:2]=2[N:24]2[CH2:29][CH2:28][CH2:27][C@@H:26]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:35])([CH3:34])[CH3:36])[CH2:25]2)[NH:12][CH:13]=1)=[O:17]

Participants

Conditions

Temperature: 155 °C

Procedure

N-(4-Chloro-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrazine-2-carboxamide (0.230 g, 0.673 mmol) and (R)-tert-butyl piperidin-3-ylcarbamate (0.404 g, 2.02 mmol) were placed in n-BuOH (3 mL) and heated to 155° C. for 18 hours in a sealed tube. The reaction was then cooled to room temperature and concentrated to dryness. The resulting residue was purified by C-18 reverse phase flash chromatography (Biotage SP4 unit, C-18 25M column, 5-75% CH3CN/water gradient; 25 CV) to give (R)-tert-butyl 1-(3-(pyrazine-2-carboxamido)-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (0.120 g, 35% yield).

Workup

temperatureThe reaction was then cooled to room temperature
concentrationconcentrated to dryness
customThe resulting residue was purified by C-18 reverse phase flash chromatography (Biotage SP4 unit

Sources & evidence

ORD record: ord-7e594e3abf91416c86052129bfbab088
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08981085B2

Reaction notes

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