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 42230노트

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HRID 42230 반응식
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

참가 물질

5

반응물 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, 화합물

생성물 1

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

시약·촉매·용매 1

HCID 178418397HCID 178418397, 화합물촉매

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온도
80 °C

실험 절차

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%).

후처리

  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

출처 및 근거

ORD 기록
ord-a7ba8844a6d94eab98e9a46b1d45ef2a
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08536168B2

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