Dimethylformamide → tert-butyl 4-[4-(2-{3-[3-(3,5-difluorophenyl)-6-oxo-6H-pyridazin-1-ylmethyl]phenyl}oxazol-5-yl)pyrazol-1-yl]piperidine-1-carboxylate

HRID 467510노트

반응식

HRID 467510 반응식
CN(C=O)C.Br[C:7]1[O:11][C:10]([C:12]2[CH:13]=[C:14]([CH:31]=[CH:32][CH:33]=2)[CH2:15][N:16]2[C:21](=[O:22])[CH:20]=[CH:19][C:18]([C:23]3[CH:28]=[C:27]([F:29])[CH:26]=[C:25]([F:30])[CH:24]=3)=[N:17]2)=[N:9][CH:8]=1.CC1(C)C(C)(C)OB([C:42]2[CH:43]=[N:44][N:45]([CH:47]3[CH2:52][CH2:51][N:50]([C:53]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[O:54])[CH2:49][CH2:48]3)[CH:46]=2)O1.O.O.O.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C(N(CC)CC)C.COCCOC.C1COCC1.[Pd](Cl)Cl>[F:30][C:25]1[CH:24]=[C:23]([C:18]2[CH:19]=[CH:20][C:21](=[O:22])[N:16]([CH2:15][C:14]3[CH:13]=[C:12]([C:10]4[O:11][C:7]([C:42]5[CH:43]=[N:44][N:45]([CH:47]6[CH2:48][CH2:49][N:50]([C:53]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[O:54])[CH2:51][CH2:52]6)[CH:46]=5)=[CH:8][N:9]=4)[CH:33]=[CH:32][CH:31]=3)[N:17]=2)[CH:28]=[C:27]([F:29])[CH:26]=1

참가 물질

9

반응물 4

HCID 6228DimethylformamideHCID 18407952Tripotassium phosphate trihydrateHCID 45480279tert-butyl 4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylateHCID 584972522-[3-(5-bromooxazol-2-yl)benzyl]-6-(3,5-difluorophenyl)-2H-pyridazin-3-one

생성물 1

HCID 58497250tert-butyl 4-[4-(2-{3-[3-(3,5-difluorophenyl)-6-oxo-6H-pyridazin-1-ylmethyl]phenyl}oxazol-5-yl)pyrazol-1-yl]piperidine-1-carboxylate

시약·촉매·용매 4

HCID 8471Triethylamine촉매HCID 24290Palladium Chloride촉매HCID 8028Tetrahydrofuran용매HCID 80711,2-Dimethoxyethane용매

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온도
80 °C

실험 절차

21 mg (0.029 mmol) of bistriphenylphosphine)palladium(II) chloride, one drop of triethylamine and 200 μl of DMF are added to a suspension, kept under nitrogen, of 131 mg (0.294 mmol) of 2-[3-(5-bromooxazol-2-yl)benzyl]-6-(3,5-difluorophenyl)-2H-pyridazin-3-one, 144 mg (0.382 mmol) of tert-butyl 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazol-1-yl]-piperidine-1-carboxylate and 135 mg (0.382 mmol) of tripotassium phosphate trihydrate in 1.2 ml of 1,2-dimethoxyethane, and the mixture is stirred at 80° C. for 18 hours. The reaction mixture is diluted with THF and filtered off with suction. The filtrate is washed twice with saturated sodium chloride solution, dried over sodium sulfate and evaporated. The residue is chromatographed on a silica-gel column with dichloromethane/methanol, giving tert-butyl 4-[4-(2-{3-[3-(3,5-difluorophenyl)-6-oxo-6H-pyridazin-1-ylmethyl]phenyl}oxazol-5-yl)pyrazol-1-yl]piperidine-1-carboxylate as yellow-ish crystals; ESI 615.

후처리

  1. filtrationfiltered off with suction
  2. washThe filtrate is washed twice with saturated sodium chloride solution
  3. dry with materialdried over sodium sulfate
  4. customevaporated
  5. customThe residue is chromatographed on a silica-gel column with dichloromethane/methanol

출처 및 근거

ORD 기록
ord-65be4291df3b4f8386e4451ab30537e7
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08623870B2

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