Triethylamine → tert-butyl (5-bromo-3-(3-phenylisoxazol-5-yl)pyrazin-2-yl)-N-tert-butoxycarbonyl-carbamate

HRID 78715

Reaction equation

HRID 78715 reaction equation
C1C(=O)N(Cl)C(=O)C1.[CH:9](=[N:16][OH:17])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[Br:18][C:19]1[N:20]=[C:21]([C:40]#[CH:41])[C:22]([N:25]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[N:23][CH:24]=1.CCN(CC)CC>CN(C=O)C>[Br:18][C:19]1[N:20]=[C:21]([C:40]2[O:17][N:16]=[C:9]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)[CH:41]=2)[C:22]([N:25]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[C:26](=[O:32])[O:27][C:28]([CH3:30])([CH3:31])[CH3:29])=[N:23][CH:24]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 12143(Z)-Benzaldehyde oximeHCID 31398ChlorosuccinimideHCID 58070394tert-butyl N-(5-bromo-3-ethynylpyrazin-2-yl)-N-[(tert-butoxy)carbonyl]carbamate

Product 1

HCID 59472363tert-butyl (5-bromo-3-(3-phenylisoxazol-5-yl)pyrazin-2-yl)-N-tert-butoxycarbonyl-carbamateYield 46%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
55 °C

Procedure

NCS (12.19 g, 91.26 mmol) was added to a solution of benzaldehyde oxime (10.05 g, 82.96 mmol) in DMF (40.20 mL) and the mixture heated at 55° C. for 15 minutes. The reaction mixture was cooled to ambient temperature and tert-butyl N-(5-bromo-3-ethynyl-pyrazin-2-yl)-N-tert-butoxycarbonyl-carbamate (36.34 g, 91.26 mmol) and DMF (30.15 mL) were added followed by the dropwise addition of Et3N (10.07 g, 13.87 mL, 99.55 mmol). The reaction mixture was stirred at ambient temperature for 45 minutes and then heated to 65° C. for 1 hour. The reaction mixture was cooled to ambient temperature and the solvent removed under high vacuum. The residue was taken up in ethyl acetate (50 ml). Remaining solid was filtered off and the filtrate concentrated in vacuo and then purified by column chromatography on silica using the ISCO column companion system, eluting with ethyl acetate/petroleum ether (0-40% EtOAc). Product fractions were combined and concentrated in vacuo to give tert-butyl (5-bromo-3-(3-phenylisoxazol-5-yl)pyrazin-2-yl)-N-tert-butoxycarbonyl-carbamate as a pale yellow solid (19 g, 46%). LC/MS m/z 419 [M−100+1]+.

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. temperatureheated to 65° C. for 1 hour
  3. temperatureThe reaction mixture was cooled to ambient temperature
  4. customthe solvent removed under high vacuum
  5. filtrationwas filtered off
  6. concentrationthe filtrate concentrated in vacuo
  7. custompurified by column chromatography on silica using the ISCO column companion system
  8. washeluting with ethyl acetate/petroleum ether (0-40% EtOAc)
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-dfb1fbf9dd21453387a43546f9c25264
Source dataset
uspto-grants-2014_09
Patent number
US08841449B2

Linked notes

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