3-Bromo-6-chloroimidazo(1,2-b)pyridazine → (6-Chloroimidazo[1,2-b]pyridazin-3-yl)(1-methyl-1H-indazol-5-yl)methanol

HRID 1892324노트

반응식

HRID 1892324 반응식
Br[C:2]1[N:6]2[N:7]=[C:8]([Cl:11])[CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1.[CH3:12][N:13]1[C:21]2[C:16](=[CH:17][C:18]([CH:22]=[O:23])=[CH:19][CH:20]=2)[CH:15]=[N:14]1>C1COCC1>[Cl:11][C:8]1[CH:9]=[CH:10][C:5]2[N:6]([C:2]([CH:22]([C:18]3[CH:17]=[C:16]4[C:21](=[CH:20][CH:19]=3)[N:13]([CH3:12])[N:14]=[CH:15]4)[OH:23])=[CH:3][N:4]=2)[N:7]=1

참가 물질

4

반응물 2

HCID 128723233-Bromo-6-chloroimidazo(1,2-b)pyridazineHCID 378185941-Methyl-1H-indazole-5-carboxaldehyde

생성물 1

HCID 58190458(6-Chloroimidazo[1,2-b]pyridazin-3-yl)(1-methyl-1H-indazol-5-yl)methanol수율 73.3%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

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온도
-10 °C

실험 절차

To a solution of 3-bromo-6-chloroimidazo[1,2-b]pyridazine (232.0 mg, 1.00 mmol) in THF (5 mL) was added EtMaBr (1M in THF, 1.50 mL, 1.50 mmol) at −10° C. After stirring at −10° C. for 1 h, 1-methyl-1H-indazole-5-carbaldehyde (240.0 mg, 1.50 mmol) was added. The mixture was allowed to warm to it slowly and stirred for 2 h. The reaction was quenched with saturated NH4Cl solution and concentrated under reduced pressure. The residue was diluted with water and extracted with EtOAc twice. The organic layers were combined, dried over Na2SO4 and concentrated. The crude product was washed with DCM to give the title compound as a white solid (230 mg, 70%). 1H-NMR (400 MHz, DMSO-d6) δ ppm 8.21 (d, 1H), 8.02 (s, 1H), 7.81 (s, 1H), 7.59 (d, 1H), 7.56 (s, 1H), 7.49 (d, 1H), 7.35 (d, 1H), 6.29 (d, 1H), 6.21 (d, 1H), 4.02 (s, 3H). LCMS (method A): [MH]+=314, tR=4.44 min.

후처리

  1. temperatureto warm to it slowly
  2. stirringstirred for 2 h
  3. customThe reaction was quenched with saturated NH4Cl solution
  4. concentrationconcentrated under reduced pressure
  5. additionThe residue was diluted with water
  6. extractionextracted with EtOAc twice
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. washThe crude product was washed with DCM

출처 및 근거

ORD 기록
ord-c6a5ee17fed24995a73a288de2477c62
출처 데이터셋
uspto-grants-2013_08
특허 번호
US08507676B2

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