(S)-tert-butyl (1-((9-bromo-6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate → (S)-tert-butyl (1-((9-cyano-6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate

HRID 1398297Notes

Reaction equation

HRID 1398297 reaction equation
Br[C:2]1[C:17]([O:18][CH2:19][C@@H:20]([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])[CH2:21][CH:22]([CH3:24])[CH3:23])=[CH:16][C:5]2[N:6]([CH3:15])[C:7](=[O:14])[C:8]3[C:13]([C:4]=2[CH:3]=1)=[CH:12][CH:11]=[N:10][CH:9]=3.[C:33]([Cu])#[N:34]>CC(N(C)C)=O.C(OCC)(=O)C>[C:33]([C:2]1[C:17]([O:18][CH2:19][C@@H:20]([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:29])([CH3:30])[CH3:31])[CH2:21][CH:22]([CH3:23])[CH3:24])=[CH:16][C:5]2[N:6]([CH3:15])[C:7](=[O:14])[C:8]3[C:13]([C:4]=2[CH:3]=1)=[CH:12][CH:11]=[N:10][CH:9]=3)#[N:34]

Participants

5

Reactant 2

HCID 86710307(S)-tert-butyl (1-((9-bromo-6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamateHCID 178418546HCID 178418546, compound

Product 1

HCID 86710309(S)-tert-butyl (1-((9-cyano-6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
150 °C

Procedure

In a 25 mL sealed tube, (S)-tert-butyl (1-((9-bromo-6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (150 mg, 0.297 mmol) (as prepared in Ex. 3, Part A) was taken up in DMA (4 mL). To this mixture was added CuCN (53.3 mg, 0.595 mmol) and the mixture heated at 150° C. for 24 h. The reaction mixture was cooled to room temperature and diluted with ethyl acetate (20 mL) and filtered through diatomaceous earth (Celite®). The ethyl acetate solution was washed with brine (10 mL) and water (10 mL). The organic layer was dried over sodium sulfate and concentrated under reduced pressure to afford the crude product as gummy solid which was carried forward without further purification. LC/MS (ESI) m/e 451.2 [(M+H)+, calcd for C25H31N4O4, 451.5]; LC/MS retention time (method B): tR=2.02 min.

Workup

  1. customIn a 25 mL sealed tube
  2. temperatureThe reaction mixture was cooled to room temperature
  3. filtrationfiltered through diatomaceous earth (Celite®)
  4. washThe ethyl acetate solution was washed with brine (10 mL) and water (10 mL)
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-b71062b0a65949989a5834e792c5b9c6
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

Loading…