1,3,3-Trimethyl-6-azabicyclo(3.2.1)octane → Ethyl 8-fluoro-4-methyl-1-oxo-9-(1,3,3-trimethyl-6-azabicyclo[3.2.1]oct-6-yl)-1,4-dihydrobenzo[f] [1,7]naphthyridine-2-carboxylate

HRID 413045노트

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HRID 413045 반응식
[F:1][C:2]1[C:22](F)=[CH:21][C:5]2[C:6]3[C:7](=[O:20])[C:8]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:9][N:10]([CH3:14])[C:11]=3[CH:12]=[N:13][C:4]=2[CH:3]=1.[CH3:24][C:25]12[CH2:32][CH:29]([NH:30][CH2:31]1)[CH2:28][C:27]([CH3:34])([CH3:33])[CH2:26]2>CS(C)=O>[F:1][C:2]1[C:22]([N:30]2[CH2:31][C:25]3([CH3:24])[CH2:32][CH:29]2[CH2:28][C:27]([CH3:34])([CH3:33])[CH2:26]3)=[CH:21][C:5]2[C:6]3[C:7](=[O:20])[C:8]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:9][N:10]([CH3:14])[C:11]=3[CH:12]=[N:13][C:4]=2[CH:3]=1

참가 물질

4

반응물 2

HCID 1037871,3,3-Trimethyl-6-azabicyclo(3.2.1)octaneHCID 18523355Ethyl 8,9-difluoro-4-methyl-1-oxo-1,4-dihydrobenzo[f][1,7]naphthyridine-2-carboxylate

생성물 1

HCID 18523295Ethyl 8-fluoro-4-methyl-1-oxo-9-(1,3,3-trimethyl-6-azabicyclo[3.2.1]oct-6-yl)-1,4-dihydrobenzo[f] [1,7]naphthyridine-2-carboxylate수율 31.7%

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매

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온도
90 °C

실험 절차

A suspension of 2 g of ethyl 8,9-difluoro-4-methyl-1-oxo-1,4-dihydrobenzo[f][1,7]naphthyridine-2-carboxylate and 2.6 g of 1,3,3-trimethyl-6-azabicyclo[3.2.1]octane in 50 cm3 of dimethyl sulphoxide was heated, with stirring, at a temperature of 90° C. for 12 days. After cooling to 20° C., the mixture was poured into 200 cm3 of ice-cold water. The medium was extracted 3 times with 200 cm3 of dichloromethane, and the organic extracts were washed 3 times with 100 cm3 of water, and dried over sodium sulphate. After filtration and concentration under reduced pressure (5.2 kPa), the compound obtained was purified by chromatography on 160 g of silica gel (0.06-0.20 mm). Elution was carried out with 3 liters of a dichloromethane-ethanol mixture (97-3 by volume), collecting 200 cm3 fractions. The fractions between 1.65 and 3 liters were concentrated to dryness under reduced pressure (5.2 kPa). 0.9 g of ethyl 8-fluoro-4-methyl-1-oxo-9-(1,3,3-trimethyl-6-azabicyclo[3.2.1]oct-6-yl)-1,4-dihydrobenzo[f][1,7]naphthyridine-2-carboxylate was obtained in the form of yellow crystals, which melted at 187° C.

후처리

  1. temperaturewas heated
  2. temperatureAfter cooling to 20° C.
  3. extractionThe medium was extracted 3 times with 200 cm3 of dichloromethane
  4. washthe organic extracts were washed 3 times with 100 cm3 of water
  5. dry with materialdried over sodium sulphate
  6. filtrationAfter filtration and concentration under reduced pressure (5.2 kPa)
  7. customthe compound obtained
  8. customwas purified by chromatography on 160 g of silica gel (0.06-0.20 mm)
  9. washElution
  10. customcollecting 200 cm3 fractions
  11. concentrationThe fractions between 1.65 and 3 liters were concentrated to dryness under reduced pressure (5.2 kPa)

출처 및 근거

ORD 기록
ord-433c4b383b2b46a3bc3504c914469148
출처 데이터셋
uspto-grants-2003_05
특허 번호
US06566362B2

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