N-(4-Methoxybenzyl)aniline → 6-chloro-N-(4-methoxybenzyl)-N-phenylimidazo[1,2-b]pyridazin-8-amine

HRID 1943496

반응식

HRID 1943496 반응식
[CH3:1][O:2][C:3]1[CH:16]=[CH:15][C:6]([CH2:7][NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.CC(C)([O-])C.[K+].Br[C:24]1[C:25]2[N:26]([CH:31]=[CH:32][N:33]=2)[N:27]=[C:28]([Cl:30])[CH:29]=1>C1COCC1>[Cl:30][C:28]1[CH:29]=[C:24]([N:8]([CH2:7][C:6]2[CH:15]=[CH:16][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:25]2[N:26]([CH:31]=[CH:32][N:33]=2)[N:27]=1

참가 물질

5

반응물 3

HCID 408377N-(4-Methoxybenzyl)anilineHCID 23665647Potassium tert-butoxideHCID 468352698-Bromo-6-chloroimidazo(1,2-b)pyridazine

생성물 1

HCID 596245586-chloro-N-(4-methoxybenzyl)-N-phenylimidazo[1,2-b]pyridazin-8-amine수율 83%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

A solution of N-(4-methoxybenzyl)aniline (6.42 g, 30.10 mmol) in THF (10 mL) was stirred at 25° C., and potassium tert-butoxide (1M in THF, 90.30 mL, 90.30 mmol) was added. After 30 minutes, 8-bromo-6-chloroimidazo[1,2-b]pyridazine (7.00 g, 30.10 mmol, Example 1 from WO 2007/038314) was added, and the reaction solution stirred at room temperature for 2 hours. The reaction was quenched with water (50 mL) and extracted with ethyl acetate (2×200 mL). The organic layer was washed with saturated aqueous NaHCO3 (100 mL) and saturated aqueous at NaCl (100 mL). The organic phase was dried Na2SO4, filtered and concentrated in vacuo. The residue was purified via ISCO (5% EtOAC/DCM; 120 g column) to give 6-chloro-N-(4-methoxybenzyl)-N-phenylimidazo[1,2-b]pyridazin-8-amine (9.09 g, 83% yield) as a tan solid. LC/MS (Phenomenex Luna 5 micron C18 4.6×30 mm, 0 to 100 B in 2 min with 1 min hold time, Flow rate=5 mL/min, detection at 254 nm, Solvent A: 10% methanol/90% water/0.1% TFA; Solvent B: 10% water/90% methanol/0.1% TFA). Rt=3.918 minutes [M+H]=365.07.

후처리

  1. customThe reaction was quenched with water (50 mL)
  2. extractionextracted with ethyl acetate (2×200 mL)
  3. washThe organic layer was washed with saturated aqueous NaHCO3 (100 mL) and saturated aqueous at NaCl (100 mL)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified via ISCO (5% EtOAC/DCM; 120 g column)

출처 및 근거

ORD 기록
ord-ed89a18303a6419cad54e59ec5fdf633
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08389527B2

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