Water → 3-Bromo-6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazine

HRID 1890683노트

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HRID 1890683 반응식
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH:9]1[CH2:13][CH2:12][CH2:11][NH:10]1.[Br:14][C:15]1[N:19]2[N:20]=[C:21](Cl)[CH:22]=[CH:23][C:18]2=[N:17][CH:16]=1.[F-].[K+].O>CS(C)=O.ClCCl>[Br:14][C:15]1[N:19]2[N:20]=[C:21]([N:10]3[CH2:11][CH2:12][CH2:13][CH:9]3[C:3]3[CH:4]=[C:5]([F:8])[CH:6]=[CH:7][C:2]=3[F:1])[CH:22]=[CH:23][C:18]2=[N:17][CH:16]=1

참가 물질

7

반응물 4

HCID 962WaterHCID 522689Potassium FluorideHCID 128723233-Bromo-6-chloroimidazo(1,2-b)pyridazineHCID 246978582-(2,5-Difluorophenyl)pyrrolidine

생성물 1

HCID 583354643-Bromo-6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazine

시약·촉매·용매 2

HCID 679Dimethyl Sulfoxide용매HCID 6344Dichloromethane용매

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온도
130 °C

실험 절차

In step 6A-4, 2-(2,5-difluorophenyl)pyrrolidine (6-5) (1.7 g, 9.3 mmol) was added to a solution of 3-bromo-6-chloroimidazo[1,2-b]pyridazine (11-1) (1.1 g, 230.92) and potassium fluoride (2.7 g, 46 mmol) in DMSO (10 mL). The resulting solution was heated to 130° C. and stirred over-night. The resulting dark orange slurry was cooled to room temperature, poured into 50 mL of DI water and extracted with ethyl acetate (3×150 mL). The ethyl acetate was dried with sodium sulfate and then removed to yield an orange solid. This solid was reconstituted with minimal amounts of dichloromethane (DCM) and purified using a silica gel column (40 g, ISCO) and a 0-5% gradient of methanol:DCM over a 20 minute period followed by 5% methanol for an additional 10 minutes. The solvent was removed from the desired fractions to yield 3-bromo-6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazine (6-6) as a light yellow solid. m/z=379.2 [M+1].

후처리

  1. temperatureThe resulting dark orange slurry was cooled to room temperature
  2. extractionextracted with ethyl acetate (3×150 mL)
  3. dry with materialThe ethyl acetate was dried with sodium sulfate
  4. customremoved
  5. customto yield an orange solid
  6. custompurified
  7. customThe solvent was removed from the desired fractions

출처 및 근거

ORD 기록
ord-f53edd717dad45b2a8bf264da41eb37d
출처 데이터셋
uspto-grants-2013_08
특허 번호
US08507488B2

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