Dimethylformamide → N-{2-fluoro-5-[(2-{[(2,2,3,3-tetramethylcyclopropyl)carbonyl]amino}imidazo[1,2-b]pyridazin-6-yl)oxy]phenyl}-1,3-dimethyl-1H-pyrazole-5-carboxamide

HRID 1663864

반응식

HRID 1663864 반응식
[CH3:1][C:2]1([CH3:10])[C:4]([CH3:6])([CH3:5])[CH:3]1[C:7]([OH:9])=O.CN(C)C=O.C(Cl)(=O)C(Cl)=O.Cl.[NH2:23][C:24]1[N:25]=[C:26]2[CH:31]=[CH:30][C:29]([O:32][C:33]3[CH:34]=[CH:35][C:36]([F:49])=[C:37]([NH:39][C:40]([C:42]4[N:46]([CH3:47])[N:45]=[C:44]([CH3:48])[CH:43]=4)=[O:41])[CH:38]=3)=[N:28][N:27]2[CH:50]=1.C(=O)([O-])O.[Na+]>O1CCCC1.CN(C)C(=O)C>[F:49][C:36]1[CH:35]=[CH:34][C:33]([O:32][C:29]2[CH:30]=[CH:31][C:26]3[N:27]([CH:50]=[C:24]([NH:23][C:7]([CH:3]4[C:4]([CH3:5])([CH3:6])[C:2]4([CH3:1])[CH3:10])=[O:9])[N:25]=3)[N:28]=2)=[CH:38][C:37]=1[NH:39][C:40]([C:42]1[N:46]([CH3:47])[N:45]=[C:44]([CH3:48])[CH:43]=1)=[O:41]

참가 물질

8

반응물 5

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 1521152,2,3,3-Tetramethylcyclopropanecarboxylic acidHCID 516892Sodium BicarbonateHCID 57505567N-{5-[(2-aminoimidazo[1,2-b]pyridazin-6-yl)oxy]-2-fluorophenyl}-1,3-dimethyl-1H-pyrazole-5-carboxamide hydrochloride

생성물 1

HCID 57505600N-{2-fluoro-5-[(2-{[(2,2,3,3-tetramethylcyclopropyl)carbonyl]amino}imidazo[1,2-b]pyridazin-6-yl)oxy]phenyl}-1,3-dimethyl-1H-pyrazole-5-carboxamide수율 19%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 31374Dimethylacetamide용매

실험 절차

To a solution of 2,2,3,3-tetramethylcyclopropanecarboxylic acid (102 mg, 0.72 mmol) in tetrahydrofuran (4.0 mL) were added N,N-dimethylformamide (20 μL, 0.26 mmol) and oxalyl chloride (63 mL, 0.72 mmol), and the mixture was stirred at room temperature for 30 min. The reaction mixture was added to a solution of N-{5-[(2-aminoimidazo[1,2-b]pyridazin-6-yl)oxy]-2-fluorophenyl}-1,3-dimethyl-1H-pyrazole-5-carboxamide.hydrochloride (200 mg, 0.48 mmol) in N,N-dimethylacetamide (4.0 mL), and the mixture was stirred at room temperature for 3 hr. Saturated aqueous sodium hydrogencarbonate solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate/tetrahydrofuran, washed with saturated brine, dried over anhydrous sodium sulfate, and filtrated. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane=3/1) and precipitated from hexane/ethyl acetate to give the title compound (46 mg, 19%) as a white powder.

후처리

  1. stirringthe mixture was stirred at room temperature for 3 hr
  2. extractionthe mixture was extracted with ethyl acetate/tetrahydrofuran
  3. washwashed with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltrated
  6. customThe solvent was evaporated under reduced pressure
  7. customthe residue was purified by silica gel column chromatography (ethyl acetate/hexane=3/1)
  8. customprecipitated from hexane/ethyl acetate

출처 및 근거

ORD 기록
ord-8064107b2c63428daaf7a6593cf55db9
출처 데이터셋
uspto-grants-2011_10
특허 번호
US08034812B2

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