2-fluoro-N-methoxy-N,5-dimethylnicotinamide → Tert-butyl 4-(6-(2-fluoro-5-methylnicotinoyl)pyridin-2-yl)-1,4-diazepane-1-carboxylate

HRID 401484

반응식

HRID 401484 반응식
Br[C:2]1[N:7]=[C:6]([N:8]2[CH2:14][CH2:13][CH2:12][N:11]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:10][CH2:9]2)[CH:5]=[CH:4][CH:3]=1.[F:22][C:23]1[N:34]=[CH:33][C:32]([CH3:35])=[CH:31][C:24]=1[C:25](N(OC)C)=[O:26]>O1CCCC1>[F:22][C:23]1[N:34]=[CH:33][C:32]([CH3:35])=[CH:31][C:24]=1[C:25]([C:2]1[N:7]=[C:6]([N:8]2[CH2:14][CH2:13][CH2:12][N:11]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:10][CH2:9]2)[CH:5]=[CH:4][CH:3]=1)=[O:26]

참가 물질

4

반응물 2

HCID 576904762-fluoro-N-methoxy-N,5-dimethylnicotinamideHCID 70700340tert-Butyl 4-(6-bromopyridin-2-yl)-1,4-diazepane-1-carboxylate

생성물 1

HCID 57690501Tert-butyl 4-(6-(2-fluoro-5-methylnicotinoyl)pyridin-2-yl)-1,4-diazepane-1-carboxylate수율 87%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
-78 °C

실험 절차

To a solution of tert-butyl 4-(6-bromopyridin-2-yl)-1,4-diazepane-1-carboxylate (898 mg, 2.52 mmol) in tetrahydrofuran (10 ml) at −78° C. was added a 2.5M solution of nbutyllithium in hexanes (1.01 ml, 2.52 mmol) dropwise maintaining the temperature at −78° C. After complete addition, the solution was stirred at −78° C. for a further 20 minutes. A solution of 2-fluoro-N-methoxy-N,5-dimethylnicotinamide (500 mg, 2.52 mmol) in tetrahydrofuran (5 ml) was added dropwise at −78° C. and the reaction mixture was stirred at −78° C. for 1 hour. The reaction was quenched with a saturated solution of ammonium chloride. The mixture was stirred at room temperature for 20 minutes and extracted into ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified on silica gel by flash column chromatography (ISCO Companion□, 40 g column, 0-20% EtOAc/Petrol) to afford the title compound as a sticky green oil (906 mg, 87% yield).

후처리

  1. additionAfter complete addition
  2. stirringthe reaction mixture was stirred at −78° C. for 1 hour
  3. customThe reaction was quenched with a saturated solution of ammonium chloride
  4. stirringThe mixture was stirred at room temperature for 20 minutes
  5. extractionextracted into ethyl acetate
  6. washThe organic layer was washed with brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified on silica gel by flash column chromatography (ISCO Companion□, 40 g column, 0-20% EtOAc/Petrol)

출처 및 근거

ORD 기록
ord-8d8b211561ab4607851f7c9b8d6e7bd7
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08741931B2

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