Diisopropylethylamine → tert-butyl (R)-1-(5-bromo-3-((S)-2-hydroxypropanamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)pyrrolidin-3-ylcarbamate

HRID 408415Notes

Reaction equation

[Br:1][C:2]1[C:3](F)=[C:4]2[C:10]([NH:11][C:12](=[O:16])[C@@H:13]([OH:15])[CH3:14])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[NH:18]1[CH2:22][CH2:21][C@@H:20]([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH2:19]1.CCN(C(C)C)C(C)C.CC#N.O>CCCCO>[Br:1][C:2]1[C:3]([N:18]2[CH2:22][CH2:21][C@@H:20]([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:28])([CH3:27])[CH3:29])[CH2:19]2)=[C:4]2[C:10]([NH:11][C:12](=[O:16])[C@@H:13]([OH:15])[CH3:14])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1

Participants

Conditions

Temperature: 135 °C

Procedure

(S)—N-(5-Bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-hydroxypropanamide (0.040 g, 0.13 mmol), (R)-tert-butyl pyrrolidin-3-ylcarbamate (0.074 g, 0.40 mmol) and DIEA (0.069 mL, 0.40 mmol, d 0.742) were placed in n-BuOH (1 mL) and heated to 135° C. for 8 hours. The reaction was then cooled to room temperature and concentrated to dryness. The resulting residue was purified by reverse phase chromatography (Biotage SP4, C-18 25M+, 0-60% CH3CN/water) to give tert-butyl (R)-1-(5-bromo-3-((S)-2-hydroxypropanamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)pyrrolidin-3-ylcarbamate (0.040 g, 65% yield).

Workup

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

Sources & evidence

ORD record: ord-ea57212b86dc46b1afd171824048273c
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08758830B2

Reaction notes

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