Dimethylformamide → 9-Chloro-5,6-dihydroimidazo[1,2-d]pyrido[3,4-f][1,4]oxazepine-2-carbaldehyde

HRID 1498452노트

반응식

HRID 1498452 반응식
C([Mg]Br)C.[Cl:5][C:6]1[N:20]=[CH:19][C:9]2[C:10]3[N:11]([CH:15]=[C:16](I)[N:17]=3)[CH2:12][CH2:13][O:14][C:8]=2[CH:7]=1.CN(C)[CH:23]=[O:24]>O1CCCC1>[Cl:5][C:6]1[N:20]=[CH:19][C:9]2[C:10]3[N:11]([CH:15]=[C:16]([CH:23]=[O:24])[N:17]=3)[CH2:12][CH2:13][O:14][C:8]=2[CH:7]=1

참가 물질

5

반응물 3

HCID 6228DimethylformamideHCID 582047809-Chloro-2-iodo-5,6-dihydroimidazo[1,2-d]pyrido[3,4-f][1,4]oxazepineHCID 178418443HCID 178418443, 화합물

생성물 1

HCID 582044299-Chloro-5,6-dihydroimidazo[1,2-d]pyrido[3,4-f][1,4]oxazepine-2-carbaldehyde수율 98.5%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

Ethylmagnesium bromide (3.0 M in Et2O, 100 mmol, 33.3 mL) was added dropwise to a solution of 9-chloro-2-iodo-5,6-dihydroimidazo[1,2-d]pyrido[3,4-f][1,4]oxazepine (10.0 g, 28.8 mmol) in tetrahydrofuran (173 mL) at −20° C. The mixture was maintained at this temperature 20 min and then allowed to warm to ambient temperature for a 1 hr period. At this point, the reaction was re-cooled to −20° C. and N,N-dimethylformamide (8.9 mL, 115 mmol) was added to the mixture. Stirring was continued for 16 h before quenching with saturated aqueous ammonium chloride solution (220 mL) and further dilution with EtOAc (250 mL). The phases were separated and the aqueous layer was extracted twice with EtOAc. The combined organic portions were washed once with brine, dried over MgSO4, filtered and concentrated in vacuo. This provided 7.08 g (98% yield) of 9-chloro-5,6-dihydroimidazo[1,2-d]pyrido[3,4-f][1,4]oxazepine-2-carbaldehyde as a yellow solid in >95% purity as determined by analytical HPLC. MS(ESI+): m/z 249.8 (M+H+), calc. 249.65

후처리

  1. temperatureThe mixture was maintained at this temperature 20 min
  2. temperatureAt this point, the reaction was re-cooled to −20° C.
  3. custombefore quenching with saturated aqueous ammonium chloride solution (220 mL) and further dilution with EtOAc (250 mL)
  4. customThe phases were separated
  5. extractionthe aqueous layer was extracted twice with EtOAc
  6. washThe combined organic portions were washed once with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-7d7829a4bd0442bf849776ce4120e60b
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09198918B2

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