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Ethylenediamine → 3-Cyclobutoxymethyl-2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one

HRID 2097387
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HRID 2097387 반응식
CN(C)C=O.[CH:6]1([O:10][CH2:11][C:12]2[C:20]3[C:19](=[O:21])[N:18](COCC[Si](C)(C)C)[N:17]=[CH:16][C:15]=3[NH:14][C:13]=2[C:30]2[CH:35]=[CH:34][C:33]([O:36][CH:37]([F:39])[F:38])=[C:32]([O:40][CH:41]3[CH2:43][CH2:42]3)[CH:31]=2)[CH2:9][CH2:8][CH2:7]1.[Br-].[Li+].C(N)CN.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C(OCC)(=O)C.C(Cl)(Cl)Cl.O1CCCC1>[CH:6]1([O:10][CH2:11][C:12]2[C:20]3[C:19](=[O:21])[NH:18][N:17]=[CH:16][C:15]=3[NH:14][C:13]=2[C:30]2[CH:35]=[CH:34][C:33]([O:36][CH:37]([F:39])[F:38])=[C:32]([O:40][CH:41]3[CH2:43][CH2:42]3)[CH:31]=2)[CH2:9][CH2:8][CH2:7]1
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참가 물질

9

반응물 5

HCID 3301EthylenediamineHCID 6228DimethylformamideHCID 82050Lithium BromideHCID 2724141Tetrabutylammonium FluorideHCID 1363466633-Cyclobutoxymethyl-2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-5-(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one

생성물 1

HCID 135845021
3-Cyclobutoxymethyl-2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one
수율 47%

시약·촉매·용매 3

HCID 6212Chloroform용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

반응 조건

온도
100 °C

실험 절차

To 1 ml of N,N-dimethylformamide containing 193 mg (0.352 mmol) of 3-cyclobutoxymethyl-2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-5-(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one obtained in Example 13-(b) were added 38.2 mg (0.440 mmol) of lithium bromide, 10 μl of ethylenediamine and 3 ml of tetrahydrofuran solution containing 1M tetrabutylammonium fluoride, and the mixture was stirred at 100° C. for 8 hours while removing tetrahydrofuran. After completion of the reaction, water was added to the reaction mixture, and the precipitated solid was collected by filtration. The obtained crude solid was applied to silica gel column chromatography (Eluent; chloroform:ethyl acetate=1:0→0:1 (V/V)), the fractions containing the desired compound were concentrated under reduced pressure, and recrystallized from a mixed solvent of ethanol and water to obtain 70 mg of the title compound as a white solid. (Yield: 47%)

후처리

  1. customwhile removing tetrahydrofuran
  2. customAfter completion of the reaction, water
  3. additionwas added to the reaction mixture
  4. filtrationthe precipitated solid was collected by filtration
  5. customThe obtained crude solid

출처 및 근거

ORD 기록
ord-d99da030e52b4abd939d860506e9562b
출처 데이터셋
uspto-grants-2013_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08450319B2

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