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 42230Notes

Reaction equation

HRID 42230 reaction equation
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

Participants

5

Reactant 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, compound

Product 1

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

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
80 °C

Procedure

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%).

Workup

  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

Sources & evidence

ORD record
ord-a7ba8844a6d94eab98e9a46b1d45ef2a
Source dataset
uspto-grants-2013_09
Patent number
US08536168B2

Reaction notes

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