N-bromobutanimide → HCID 86710447, compound

HRID 1398476Notes

Reaction equation

[CH3:1][C:2]1[N:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10](=[O:12])[N:9]([CH3:13])[C:8]1[CH:14]=[C:15]([O:18][CH2:19][C@@H:20]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[CH2:21][CH:22]=[C:23]([F:25])[F:24])[CH:16]=[CH:17][C:7]2=1.[Br:34]N1C(=O)CCC1=O>C(#N)C>[Br:34][C:16]1[C:15]([O:18][CH2:19][C@@H:20]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:30])([CH3:32])[CH3:31])[CH2:21][CH:22]=[C:23]([F:25])[F:24])=[CH:14][C:8]2[N:9]([CH3:13])[C:10](=[O:12])[C:11]3[C:6]([C:7]=2[CH:17]=1)=[CH:5][CH:4]=[N:3][C:2]=3[CH3:1]

Participants

Conditions

Temperature: 80 °C

Procedure

A solution of (S)-tert-butyl (1-((4,6-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-5,5-difluoropent-4-en-2-yl)carbamate (1.03 g, 2.24 mmol) in acetonitrile (22 mL) was treated with N-bromosuccinimide (0.44 g, 2.5 mmol), heated to 80° C. for 45 min, and then concentrated under reduced pressure. The crude material was purified over SiO2 (1-4% 2M ammonia in methanol/dichloromethane gradient elution) to afford (S)-tert-butyl (1-((9-bromo-4,6-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-5,5-difluoropent-4-en-2-yl)carbamate (0.81 g, 1.51 mmol, 67% yield) as a white solid. LC/MS, (ESI) m/z 537.9 [(M+H)+, calcd for C24H27BrF2N3O4, 538.1]; 1H NMR (400 MHz, CDCl3) δ ppm 8.62 (d, J=5.8 Hz, 1H), 8.22 (s, 1H), 7.65 (d, J=5.5 Hz, 1H), 6.75 (s, 1H), 5.01 (d, J=8.3 Hz, 1H), 4.41-4.26 (m, 1H), 4.24-4.04 (m, 3H), 3.67 (s, 3H), 3.12 (s, 3H), 2.64-2.34 (m, 2H), 1.48 (s, 9H).

Workup

concentrationconcentrated under reduced pressure
customThe crude material was purified over SiO2 (1-4% 2M ammonia in methanol/dichloromethane gradient elution)

Sources & evidence

ORD record: ord-4d35bba5f7994873ae41a1f16eae8344
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08901305B2

Reaction notes

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