N,N,N',N'-Tetramethylethylenediamine → HCID 21948183, compound

HRID 1839389Notes

Reaction equation

HRID 1839389 reaction equation
[Li]N1C(C)(C)CCCC1(C)C.CC1CCCN(C)C1(C)C.CN(CCN(C)C)C.[Li]CCCC.[NH:35]([C:42]1[N:43]([C:56]2[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=2)[C:44]2[C:49]([C:50](=[O:52])[CH:51]=1)=[CH:48][C:47]([F:53])=[C:46]([O:54][CH3:55])[N:45]=2)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.[Br:62]C(Cl)(Cl)C(Cl)(Cl)Br>C1COCC1.O>[NH:35]([C:42]1[N:43]([C:56]2[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=2)[C:44]2[C:49]([C:50](=[O:52])[CH:51]=1)=[C:48]([Br:62])[C:47]([F:53])=[C:46]([O:54][CH3:55])[N:45]=2)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1

Participants

9

Reactant 6

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 694261,2-Dibromo-1,1,2,2-tetrachloroethaneHCID 187617721,2,2,3-TetramethylpiperidineHCID 21948150HCID 21948150, compoundHCID 178418339ButyllithiumHCID 178418821HCID 178418821, compound

Product 1

HCID 21948183HCID 21948183, compoundYield 16.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-40 °C

Procedure

A solution of LTMP [freshly prepared at 0° C. from tetramethylpiperidine (785.4 mg, 5.6 mmol), TMEDA (651 mg, 5.6 mmol) and n-BuLi (3.5 mL, 5.6 mmol)] in THF (10 mL) was added to a cooled (−40° C.) stirred solution of 2-anilino-6-fluoro-7-methoxy-1-phenyl-1,8-naphthyridin-4(1H)-one (507 mg, 104 mmol) in THF (20 mL). The reaction mixture was warmed to room temperature. After 1 h, the mixture was cooled to −30° C. and 1,2-dibromotetrachloroethane (457 mg, 1.4 mmol) was added. After 30 min, water (50 mL) was added slowly, and then the reaction was warmed to room temperature and extracted with EtOAc. The combined organic extracts were washed with brine, dried over Na2SO4, and concentrated in vacuo. Silica gel flash chromatography of the residue using EtOAc afforded 2-anilino-5-bromo-6-fluoro-7-methoxy-1-phenyl-1,8-naphthyridin-4(1H)-one (101 mg, 16%) as a light yellow solid: LCMS RT: 2.75 min, MH+: 440.3.

Workup

  1. additionwas added to
  2. temperatureThe reaction mixture was warmed to room temperature
  3. temperaturethe mixture was cooled to −30° C.
  4. waitAfter 30 min
  5. temperaturethe reaction was warmed to room temperature
  6. extractionextracted with EtOAc
  7. washThe combined organic extracts were washed with brine
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-eb07a9db034e403697311e94c0049d97
Source dataset
uspto-grants-2004_01
Patent number
US06677352B1

Reaction notes

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