Triphenylphosphine → 2-{3-[5-(4-methylpiperazin-1-yl)pyrimidin-2-yl]benzyl}-6-(1-methyl-1H-pyrazol-4-yl)-2H-pyridazin-3-one

HRID 1408400Notes

Reaction equation

HRID 1408400 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:8]=[CH:9][C:10](=[O:13])[NH:11][N:12]=2)[CH:4]=[N:3]1.[CH3:14][N:15]1[CH2:20][CH2:19][N:18]([C:21]2[CH:22]=[N:23][C:24]([C:27]3[CH:28]=[C:29]([CH2:33]O)[CH:30]=[CH:31][CH:32]=3)=[N:25][CH:26]=2)[CH2:17][CH2:16]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>C1COCC1.CN(C=O)C>[CH3:14][N:15]1[CH2:16][CH2:17][N:18]([C:21]2[CH:26]=[N:25][C:24]([C:27]3[CH:28]=[C:29]([CH:30]=[CH:31][CH:32]=3)[CH2:33][N:11]3[C:10](=[O:13])[CH:9]=[CH:8][C:7]([C:5]4[CH:4]=[N:3][N:2]([CH3:1])[CH:6]=4)=[N:12]3)=[N:23][CH:22]=2)[CH2:19][CH2:20]1

Participants

7

Reactant 4

HCID 11776Triphenylphosphine2×HCID 97268Di-tert-butyl azodicarboxylate2×HCID 594380436-(1-methyl-1H-pyrazol-4-yl)pyridazin-3(2H)-oneHCID 59484860{3-[5-(4-Methylpiperazin-1-yl)pyrimidin-2-yl]phenyl}methanol

Product 1

HCID 594849282-{3-[5-(4-methylpiperazin-1-yl)pyrimidin-2-yl]benzyl}-6-(1-methyl-1H-pyrazol-4-yl)-2H-pyridazin-3-one

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

71 mg (0.40 mmol) of 6-(1-methyl-1H-pyrazol-4-yl)-2H-pyridazin-3-one and 163 mg (0.40 mmol) of {3-[5-(4-methylpiperazin-1-yl)pyrimidin-2-yl]phenyl}-methanol are suspended in 3 ml of THF and 1 ml of DMF with 200 mg (0.60 mmol) of polymer-bound triphenylphosphine (about 3 mmol of triphenylphosphine per g) and shaken at room temperature for 30 min. 139 mg (0.60 mmol) of di-tert-butyl azodicarboxylate are added. The reaction mixture is shaken at room temperature for 1 h. A further 200 mg (0.6 mmol) of polymer-bound triphenylphosphine (about 3 mmol of triphenylphosphine per g) and 139 mg (0.60 mmol) of di-tert-butyl azodicarboxylate are added, and the reaction mixture is shaken at room temperature for 2 h. The reaction mixture is filtered, the residue is evaporated, and the residue is purified by means of preparative HPLC; yield: 18 mg of “A286”; HPLC: Rt=2.08 min (method C); LC-MS: 443 (M+H).

Workup

  1. stirringthe reaction mixture is shaken at room temperature for 2 h
  2. filtrationThe reaction mixture is filtered
  3. customthe residue is evaporated
  4. customthe residue is purified by means of preparative HPLC

Sources & evidence

ORD record
ord-8dc9bd74e29045bc8486980bc47f7b9c
Source dataset
uspto-grants-2014_12
Patent number
US08921357B2

Reaction notes

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