7-Chloro-4-[4-(5-trifluoromethyl-pyridin-2-yl)-piperazin-1-yl]-furo[2,3-d]pyridazine → 7-Benzyl-4-[4-(5-trifluoromethylpyridin-2-yl)piperazin-1-yl]furo[2,3-d]pyridazine

HRID 42230ノート

反応式

HRID 42230 の反応式
Cl[C:2]1[N:3]=[N:4][C:5]([N:11]2[CH2:16][CH2:15][N:14]([C:17]3[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][N:18]=3)[CH2:13][CH2:12]2)=[C:6]2[CH:10]=[CH:9][O:8][C:7]=12.ClC1N=NC(N2CCN(C3C=CC(C(F)(F)F)=CN=3)CC2)=C2OC=CC=12.[Br-].[CH2:54]([Zn+])[C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:54]([C:2]1[N:3]=[N:4][C:5]([N:11]2[CH2:12][CH2:13][N:14]([C:17]3[CH:22]=[CH:21][C:20]([C:23]([F:25])([F:24])[F:26])=[CH:19][N:18]=3)[CH2:15][CH2:16]2)=[C:6]2[CH:10]=[CH:9][O:8][C:7]=12)[C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1

参加物

5

反応物 3

HCID 441865277-Chloro-4-[4-(5-trifluoromethyl-pyridin-2-yl)-piperazin-1-yl]-furo[2,3-d]pyridazineHCID 441865284-Chloro-7-[4-(5-trifluoromethyl-pyridin-2-yl)-piperazin-1-yl]-furo[2,3-d]pyridazineHCID 178419772HCID 178419772、化合物

生成物 1

HCID 441861857-Benzyl-4-[4-(5-trifluoromethylpyridin-2-yl)piperazin-1-yl]furo[2,3-d]pyridazine収率 7%

試薬・触媒・溶媒 1

HCID 178418397HCID 178418397、化合物触媒

反応条件

温度
80 °C

実験手順

The mixture of 7-chloro-4-[4-(5-trifluoromethyl-pyridin-2-yl)-piperazin-1-yl]-furo[2,3-d]pyridazine and 4-chloro-7-[4-(5-trifluoromethyl-pyridin-2-yl)-piperazin-1-yl]-furo[2,3-d]pyridazine (210 mg, 0.547 mmol) are combined with benzyl zinc bromide (6.75 mL, 0.5M in THF, 3.28 mmol) and tetrakis (triphenylphosphine) palladium0 (31.5 mg, 0.027 mmol). The reaction is heated to 80° C. for 40 h. Add H2O and extract with EtOAc. Concentrate in vacuo. The residue is purified by flash chromatography on silica gel (EtOAc/Heptane) to afford a mix of title compounds. This mixture is separated by HPLC using a 30% isocratic gradient of CH3CN/H2O with a formic acid modifier (0.1%) to yield both title compounds (16.9 mg, 7%).

後処理

  1. extractionAdd H2O and extract with EtOAc
  2. concentrationConcentrate in vacuo
  3. customThe residue is purified by flash chromatography on silica gel (EtOAc/Heptane)
  4. customto afford
  5. additiona mix of title compounds
  6. customThis mixture is separated by HPLC

出典と根拠

ORDレコード
ord-a7ba8844a6d94eab98e9a46b1d45ef2a
出典データセット
uspto-grants-2013_09
特許番号
US08536168B2

反応ノート

読み込み中…