Triethylamine → HCID 22051110, compound

HRID 1866967Notes

Reaction equation

HRID 1866967 reaction equation
Cl.[NH2:2][C:3]1[CH:8]=[CH:7][N:6]([CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=2)[C:5](=[O:17])[C:4]=1[Br:18].C(N(CC)CC)C.[F:26][C:27]1[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[C:28]=1[C:29](Cl)=[O:30].[OH-].[Na+]>CN(C)C1C=CN=CC=1.C(#N)C>[Br:18][C:4]1[C:5](=[O:17])[N:6]([CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=2)[CH:7]=[CH:8][C:3]=1[NH:2][C:29](=[O:30])[C:28]1[C:27]([F:26])=[CH:35][CH:34]=[CH:33][C:32]=1[F:36]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 874382,6-Difluorobenzoyl chlorideHCID 22050881HCID 22050881, compound

Product 1

HCID 22051110HCID 22051110, compoundYield 43%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6342AcetonitrileSolvent

Procedure

4-amino-3-bromo-1-(3-fluorobenzyl)pyridin-2(1H)-one (from step 3) (0.30 g, 1.01 mmol) and 4-dimethylaminopyridine (0.002 g, 0.01 mmol) were suspended in acetonitrile (5 mL) followed by dropwise addition of triethylamine (0.2 mL, 1.41 mmol). This reaction mixture was stirred for 10 minutes at room temperature before being cooled to 0° C. 2,6-difluorobenzoyl chloride (0.37 g, 2.12 mmol) was added dropwise and the reaction was heated at reflux overnight. The reaction was cooled to room temperature and 1N NaOH (10 mL) was added. The reaction was then stirred for 45 minutes at room temperature. The reaction mixture was extracted with ethyl acetate (3×25 mL) and the organic layer washed with 1N NaOH (2×25 mL), H2O (until pH neutral), brine (50 mL), dried over MgSO4, concentrated, and subjected to chromatography (on C-18, acetonitrile/H2O with 0.1% trifluoracetic acid) to afford a white solid (0.19 g, 43%). 1H NMR (400 MHz, CDCl3) δ 8.42 (br s, 1H), 7.67 (d, J=7.65 Hz, 1H), 7.49 (app tt, J=6.31, 8.60 Hz, 1H), 7.33-28 (m, 2H), 7.10-6.97 (m, 5H), 5.17 (s, 2H). ES-HRMS m/z 437.0083 (M+H C19H12BrF3N2O2 requires 437.0107).

Workup

  1. temperaturebefore being cooled to 0° C
  2. temperaturethe reaction was heated
  3. temperatureat reflux overnight
  4. temperatureThe reaction was cooled to room temperature
  5. stirringThe reaction was then stirred for 45 minutes at room temperature
  6. extractionThe reaction mixture was extracted with ethyl acetate (3×25 mL)
  7. washthe organic layer washed with 1N NaOH (2×25 mL), H2O (until pH neutral), brine (50 mL)
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-b309dde294a84a6a965173341617120e
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

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