1-Bromo-2-chlorobenzene → 4-(2-Chlorophenyl)-1-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-ol

HRID 1675011노트

반응식

HRID 1675011 반응식
C([Mg]Cl)(C)C.[Cl-].[Li+].Br[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[Cl:15].[F:16][C:17]([F:35])([F:34])[C:18]1[N:22]2[N:23]=[C:24]([N:27]3[CH2:32][CH2:31][C:30](=[O:33])[CH2:29][CH2:28]3)[CH:25]=[CH:26][C:21]2=[N:20][N:19]=1>C1COCC1>[Cl:15][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=1[C:30]1([OH:33])[CH2:31][CH2:32][N:27]([C:24]2[CH:25]=[CH:26][C:21]3[N:22]([C:18]([C:17]([F:35])([F:34])[F:16])=[N:19][N:20]=3)[N:23]=2)[CH2:28][CH2:29]1

참가 물질

5

반응물 3

HCID 127541-Bromo-2-chlorobenzeneHCID 595783691-[3-(Trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-oneHCID 178461733HCID 178461733, 화합물

생성물 1

HCID 591497444-(2-Chlorophenyl)-1-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-ol수율 41.3%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

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온도
0 °C

실험 절차

Isopropylmagnesium chloride-lithium chloride complex (1.0M in THF, 10 mL, 10.00 mmol) was added dropwise to 1-bromo-2-chlorobenzene (1.91 g, 9.98 mmol) in THF (2.0 mL) cooled to 0° C. over a period of 10 minutes. The resulting solution was stirred at 0° C. for 1 hour then a 2.0 mL aliquot was added dropwise to 1-[3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-one (400 mg, 1.40 mmol) in THF (10 mL) cooled to 0° C. over a period of 10 minutes. The resulting solution was stirred at 0° C. for 10 minutes then allowed to warm slowly to room temperature and stirred for a further hour. The reaction mixture was then quenched with saturated ammonium chloride (30 mL) and extracted with EtOAc. The extract was washed with saturated brine, dried over MgSO4 and concentrated by evaporation, then purified by flash silica chromatography, eluting with EtOAc. Pure fractions were evaporated to dryness to afford 4-(2-chlorophenyl)-1-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-ol (230 mg, 41%) as a colourless solid.

후처리

  1. temperaturecooled to 0° C. over a period of 10 minutes
  2. stirringThe resulting solution was stirred at 0° C. for 10 minutes
  3. temperatureto warm slowly to room temperature
  4. stirringstirred for a further hour
  5. customThe reaction mixture was then quenched with saturated ammonium chloride (30 mL)
  6. extractionextracted with EtOAc
  7. washThe extract was washed with saturated brine
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated by evaporation
  10. custompurified by flash silica chromatography
  11. washeluting with EtOAc
  12. customPure fractions were evaporated to dryness

출처 및 근거

ORD 기록
ord-6b4912403db442ff84a6faf18689fdf3
출처 데이터셋
uspto-grants-2011_08
특허 번호
US08003649B2

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