Triethylamine → HCID 67480060, compound

HRID 509552Notes

Reaction equation

HRID 509552 reaction equation
C1C(=O)N(Cl)C(=O)C1.[F:9][C:10]1[CH:11]=[C:12]([CH:23]=[CH:24][C:25]=1[CH:26]=[N:27][OH:28])[CH2:13][N:14]([CH3:22])[C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18].[Br:29][C:30]1[CH:31]=[C:32]([C:51]#[CH:52])[C:33]([N:36]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[C:37](=[O:43])[O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[N:34][CH:35]=1.CCN(CC)CC>CN(C=O)C.C(OCC)(=O)C.O>[Br:29][C:30]1[CH:31]=[C:32]([C:51]2[O:28][N:27]=[C:26]([C:25]3[CH:24]=[CH:23][C:12]([CH2:13][N:14]([C:15]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:21])[CH3:22])=[CH:11][C:10]=3[F:9])[CH:52]=2)[C:33]([N:36]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[C:37](=[O:43])[O:38][C:39]([CH3:41])([CH3:42])[CH3:40])=[N:34][CH:35]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 31398ChlorosuccinimideHCID 76686622HCID 76686622, compoundHCID 86667790HCID 86667790, compound

Product 1

HCID 67480060HCID 67480060, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

NCS (62.52 mg, 0.4682 mmol) was added to a solution tert-butyl 3-fluoro-4-((hydroxyimino)methyl)benzyl(methyl)carbamate [prepared in an analogous manner to that described in Bioorganic & Medicinal Chemistry, 17(13), 4773-4785; 2009] (132.2 mg, 0.4682 mmol) in DMF (930.0 μL) and the mixture heated at 55° C. for 15 minutes. The reaction mixture was allowed to cool to room temperature, and tert-butyl N-(5-bromo-3-ethynyl-2-pyridyl)-N-tert-butoxycarbonyl-carbamate (186 mg, 0.4682 mmol) and Et3N (56.85 mg, 78.31 μL, 0.5618 mmol) were added. The mixture was stirred at ambient temperature for 45 minutes followed by heating to 65° C. for 1 hour. The mixture was cooled to ambient temperature and diluted with ethyl acetate (5 mL) and water (5 mL) and the layers separated. The aqueous layer was extracted further with ethyl acetate (2×5 mL) and the combined organic extracts washed with water (3×10 mL), dried over MgSO4 and concentrated in vacuo. The residue was purified by column chromatography (ISCO Companion™, 12 g column, eluting with 0 to 100% EtOAc/Petroleum Ether, loaded in DCM) to give the impure sub-title product as a tacky yellow oil. This was used in the next step without further purification.

Workup

  1. customprepared in an analogous manner to that
  2. temperatureby heating to 65° C. for 1 hour
  3. temperatureThe mixture was cooled to ambient temperature
  4. customthe layers separated
  5. extractionThe aqueous layer was extracted further with ethyl acetate (2×5 mL)
  6. washthe combined organic extracts washed with water (3×10 mL)
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by column chromatography (ISCO Companion™, 12 g column, eluting with 0 to 100% EtOAc/Petroleum Ether, loaded in DCM)

Sources & evidence

ORD record
ord-ff532445a2ae4837b68016cf4c2c09f0
Source dataset
uspto-grants-2015_08
Patent number
US09096584B2

Reaction notes

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