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

HRID 1943496

反応式

HRID 1943496 の反応式
[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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-ed89a18303a6419cad54e59ec5fdf633
出典データセット
uspto-grants-2013_03
特許番号
US08389527B2

関連ノート

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