Hydrochloric Acid → 7-Bromo-3-(2-chloro-5-fluorophenyl)-1,6-naphthyridine

HRID 468887노트

반응식

HRID 468887 반응식
CC(C)([O-])C.[K+].[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([F:14])=[CH:10][C:9]=1[CH2:15][CH:16]=O.[Br:18][C:19]1[CH:24]=[C:23]([NH:25]C(=O)OC(C)(C)C)[C:22]([CH:33]=O)=[CH:21][N:20]=1.Cl>O1CCOCC1.O.C(OCC)(=O)C>[Br:18][C:19]1[CH:24]=[C:23]2[C:22]([CH:33]=[C:15]([C:9]3[CH:10]=[C:11]([F:14])[CH:12]=[CH:13][C:8]=3[Cl:7])[CH:16]=[N:25]2)=[CH:21][N:20]=1

참가 물질

8

반응물 4

HCID 313Hydrochloric AcidHCID 23665647Potassium tert-butoxideHCID 552747552-(2-Chloro-5-fluorophenyl)acetaldehydeHCID 86674965tert-Butyl (2-bromo-5-formylpyridin-4-yl)carbamate

생성물 1

HCID 866749667-Bromo-3-(2-chloro-5-fluorophenyl)-1,6-naphthyridine수율 30%

시약·촉매·용매 3

HCID 962Water용매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매3회

실험 절차

To a slurry of potassium tert-butoxide (94 mg, 0.8 mmol) in 1,4-dioxane (1 mL) cooled at 0° C. was added 2-(2-chloro-5-fluorophenyl)acetaldehyde (98 mg, 0.4 mmol) as a solution in 1,4-dioxane (0.6 mL). The reaction mixture was stirred for 10 minutes at this temperature, and then tert-butyl 2-bromo-5-formylpyridin-4-ylcarbamate (60 mg, 0.2 mmol) was added as a solution in dioxane (0.6 mL). The reaction mixture was allowed to warm to room temperature, and after 30 minutes a 5.0M solution of hydrogen chloride in water (0.5 mL) was added and the mixture was heated at 100° C. for 1 hour. The cooled reaction mixture was diluted with ethyl acetate (50 mL) and washed with water (50 mL). The organic layer was separated, dried over sodium sulfate, filtered, and evaporated in vacuo to afford a residue that was purified by flash chromatography (silica, 4 g, ISCO, 0-50% ethyl acetate in heptane) to afford the title compound as an off-white solid (20 mg, 30%), which was used in the next step without further purification.

후처리

  1. temperaturethe mixture was heated at 100° C. for 1 hour
  2. customThe cooled reaction mixture
  3. washwashed with water (50 mL)
  4. customThe organic layer was separated
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customto afford a residue that
  9. customwas purified by flash chromatography (silica, 4 g, ISCO, 0-50% ethyl acetate in heptane)

출처 및 근거

ORD 기록
ord-84fcc6721143408589546e34daac356b
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08623889B2

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