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 467510ノート

反応式

HRID 467510 の反応式
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

参加物

9

反応物 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

生成物 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

試薬・触媒・溶媒 4

HCID 8471Triethylamine触媒HCID 24290Palladium Chloride触媒HCID 8028Tetrahydrofuran溶媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
80 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-65be4291df3b4f8386e4451ab30537e7
出典データセット
uspto-grants-2014_01
特許番号
US08623870B2

反応ノート

読み込み中…