Diisopropylethylamine → tert-butyl 2-(5-bromo-4-((R)-3-(tert-butoxycarbonylamino)piperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-ylcarbamoyl)morpholine-4-carboxylate

HRID 875808Notes

Reaction equation

[Br:1][C:2]1[C:3](F)=[C:4]2[C:10]([NH:11][C:12]([CH:14]3[O:19][CH2:18][CH2:17][N:16]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:15]3)=[O:13])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[NH:28]1[CH2:33][CH2:32][CH2:31][C@@H:30]([NH:34][C:35](=[O:41])[O:36][C:37]([CH3:40])([CH3:39])[CH3:38])[CH2:29]1.CCN(C(C)C)C(C)C>CCCCO>[Br:1][C:2]1[C:3]([N:28]2[CH2:33][CH2:32][CH2:31][C@@H:30]([NH:34][C:35]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:41])[CH2:29]2)=[C:4]2[C:10]([NH:11][C:12]([CH:14]3[O:19][CH2:18][CH2:17][N:16]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:15]3)=[O:13])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of tert-butyl 2-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-ylcarbamoyl)morpholine-4-carboxylate (660 mg, 1.49 mmol), (R)-tert-butyl piperidin-3-ylcarbamate (1.49 g, 7.44 mmol), and DIEA (1.30 mL, 7.44 mmol) in n-BuOH (6 mL) was stirred at 120° C. for 36 hours. The reaction was then cooled to room temperature and concentrated in vacuo. The crude residue was purified by reverse phase HPLC (0-50% CH3CN/water) to give the separated diastereomers of tert-butyl 2-(5-bromo-4-((R)-3-(tert-butoxycarbonylamino)piperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-ylcarbamoyl)morpholine-4-carboxylate in the following yields: diastereomer #1 (70 mg, 7.5%) diastereomer #2 (80 mg, 8.6%).

Workup

temperatureThe reaction was then cooled to room temperature
concentrationconcentrated in vacuo
customThe crude residue was purified by reverse phase HPLC (0-50% CH3CN/water)

Sources & evidence

ORD record: ord-57e77ab609804e039a051b7661c50a8f
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08981085B2

Reaction notes

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