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

HRID 1890683ノート

反応式

HRID 1890683 の反応式
[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

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 679Dimethyl Sulfoxide溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
130 °C

実験手順

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].

後処理

  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

出典と根拠

ORDレコード
ord-f53edd717dad45b2a8bf264da41eb37d
出典データセット
uspto-grants-2013_08
特許番号
US08507488B2

反応ノート

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