Ethyl (chloroformyl)acetate → Ethyl 6,8-dichloroimidazo[1,2-b]pyridazine-3-carboxylate

HRID 1943396노트

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HRID 1943396 반응식
[Cl:1]C(C=O)C(OCC)=O.BrC1C=C(Cl)N=NC=1N.Br[C:20]1[C:21]2[N:22]([C:27]([C:30]([O:32][CH2:33][CH3:34])=[O:31])=[CH:28][N:29]=2)[N:23]=[C:24]([Cl:26])[CH:25]=1>>[Cl:26][C:24]1[CH:25]=[C:20]([Cl:1])[C:21]2[N:22]([C:27]([C:30]([O:32][CH2:33][CH3:34])=[O:31])=[CH:28][N:29]=2)[N:23]=1

참가 물질

4

반응물 3

HCID 118030Ethyl (chloroformyl)acetateHCID 220244193-Amino-4-bromo-6-chloropyridazineHCID 59313730Ethyl 8-bromo-6-chloroimidazo[1,2-b]pyridazine-3-carboxylate

생성물 1

HCID 59314032Ethyl 6,8-dichloroimidazo[1,2-b]pyridazine-3-carboxylate수율 29%

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온도
90 °C

실험 절차

To a 250 mL round-bottomed flask was added ethyl 2-chloro-3-oxopropanoate (4.33 g, 28.8 mmol) and 4-bromo-6-chloropyridazin-3-amine (5 g, 23.99 mmol). The solution was heated to 90° C. for 16 hours. The solution was quenched with ethyl acetate and washed with water. The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. The crude material was purified by ISCO (10% ethyl acetate/dichloromethane; 80 g column) to give a mixture of ethyl 8-bromo-6-chloroimidazo[1,2-b]pyridazine-3-carboxylate and ethyl 6,8-dichloroimidazo[1,2-b]pyridazine-3-carboxylate (2.1 g, 29% yield). LC/MS, m/z 256.96 (M+1). HPLC Rt, 2.54 min. LC/MS, m/z 303.92 (M+1). HPLC Rt, 2.63 min. Waters Sunfire C18 column (4.6×50 mm) 0%-100% B. Solvent B: (90% MeOH, 10% H2O, 0.1% TFA). Solvent A: (10% MeOH, 90% H2O, 0.1% TFA). Gradient, start % B=0, final % B=100, gradient time 4 min, hold at 100% B 1 min, flow rate 4 mL/min.

후처리

  1. customThe solution was quenched with ethyl acetate
  2. washwashed with water
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe crude material was purified by ISCO (10% ethyl acetate/dichloromethane; 80 g column)
  6. customto give

출처 및 근거

ORD 기록
ord-ee428c6a52754a0fb7cf030865aa817b
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08389527B2

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