Triphenylphosphine → 4-{1-[3-(2,6-Dichloro-phenyl)-5-isopropyl-isoxazol-4-ylmethyl]-6-oxo-1,6-dihydro-pyridazin-3-yloxy}-benzoic acid methyl ester

HRID 215838Notes

Reaction equation

HRID 215838 reaction equation
[CH3:1][O:2][C:3](=[O:18])[C:4]1[CH:9]=[CH:8][C:7]([O:10][C:11]2[CH:16]=[CH:15][C:14](=[O:17])[NH:13][N:12]=2)=[CH:6][CH:5]=1.[Cl:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[C:21]=1[C:27]1[C:31]([CH2:32]O)=[C:30]([CH:34]([CH3:36])[CH3:35])[O:29][N:28]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1C=CC=CC=1>[CH3:1][O:2][C:3](=[O:18])[C:4]1[CH:5]=[CH:6][C:7]([O:10][C:11]2[N:12]=[N:13][C:14]([O:17][CH2:32][C:31]3[C:27]([C:21]4[C:20]([Cl:19])=[CH:25][CH:24]=[CH:23][C:22]=4[Cl:26])=[N:28][O:29][C:30]=3[CH:34]([CH3:36])[CH3:35])=[CH:15][CH:16]=2)=[CH:8][CH:9]=1.[CH3:1][O:2][C:3](=[O:18])[C:4]1[CH:5]=[CH:6][C:7]([O:10][C:11]2[CH:16]=[CH:15][C:14](=[O:17])[N:13]([CH2:32][C:31]3[C:27]([C:21]4[C:20]([Cl:19])=[CH:25][CH:24]=[CH:23][C:22]=4[Cl:26])=[N:28][O:29][C:30]=3[CH:34]([CH3:36])[CH3:35])[N:12]=2)=[CH:8][CH:9]=1

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 10850745(3-(2,6-Dichlorophenyl)-5-isopropylisoxazol-4-yl)methanolHCID 672971734-(6-Oxo-1,6-dihydro-pyridazin-3-yloxy)-benzoic acid methyl ester

Product 2

HCID 672970344-{6-[3-(2,6-Dichloro-phenyl)-5-isopropyl-isoxazol-4-ylmethoxy]-pyridazin-3-yloxy}-benzoic acid methyl esterYield 9%HCID 672970644-{1-[3-(2,6-Dichloro-phenyl)-5-isopropyl-isoxazol-4-ylmethyl]-6-oxo-1,6-dihydro-pyridazin-3-yloxy}-benzoic acid methyl esterYield 58%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

To a mixture of 4-(6-oxo-1,6-dihydro-pyridazin-3-yloxy)-benzoic acid methyl ester (0.43 g, 1.75 mmol), [3-(2,6-dichloro-phenyl)-5-isopropyl-isoxazol-4-yl]-methanol (0.50 g, 1.75 mmol) and triphenylphosphine (0.56 g, 2.1 mmol) in benzene (12 ml) was added dropwise 0.6 ml (2.9 mmol) of diisopropyl 1,2-diazenedicarboxylate (DIAD). The reaction mixture was stirred at room temperature for 27 h and the solvent was removed in vacuo. The residue was subjected to preparative HPLC purification eluting with acetonitrile/water 1:1 to provide 0.08 g (9%) of the desired 4-{6-[3-(2,6-dichloro-phenyl)-5-isopropyl-isoxazol-4-ylmethoxy]-pyridazin-3-yloxy}-benzoic acid methyl ester together with 0.52 g (58%) of 4-{1-[3-(2,6-dichloro-phenyl)-5-isopropyl-isoxazol-4-ylmethyl]-6-oxo-1,6-dihydro-pyridazin-3-yloxy}-benzoic acid methyl ester.

Workup

  1. customthe solvent was removed in vacuo
  2. customThe residue was subjected to preparative HPLC purification
  3. washeluting with acetonitrile/water 1:1

Sources & evidence

ORD record
ord-68fe0b9d9c2e4576a9331c0bd848ebf7
Source dataset
uspto-grants-2012_06
Patent number
US08193192B2

Reaction notes

Loading…