5-Amino-2-methylphthalazin-1-one → 5-{[4-(3-Fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)hexylidene]amino}-2-methylphthalazin-1-one

HRID 1362495Notes

Reaction equation

HRID 1362495 reaction equation
[F:1][C:2]1[C:3]([O:20][CH3:21])=[C:4]([CH:8]([CH2:18][CH3:19])[CH2:9][C:10]([OH:17])([C:13]([F:16])([F:15])[F:14])[CH:11]=O)[CH:5]=[CH:6][CH:7]=1.[NH2:22][C:23]1[CH:32]=[CH:31][CH:30]=[C:29]2[C:24]=1[CH:25]=[N:26][N:27]([CH3:34])[C:28]2=[O:33]>[O-]CC.[O-]CC.[O-]CC.[O-]CC.[Ti+4]>[F:1][C:2]1[C:3]([O:20][CH3:21])=[C:4]([CH:8]([CH2:18][CH3:19])[CH2:9][C:10]([OH:17])([C:13]([F:14])([F:15])[F:16])[CH:11]=[N:22][C:23]2[CH:32]=[CH:31][CH:30]=[C:29]3[C:24]=2[CH:25]=[N:26][N:27]([CH3:34])[C:28]3=[O:33])[CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 179850455-Amino-2-methylphthalazin-1-oneHCID 866153234-(3-Fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)hexanal

Product 1

HCID 669694765-{[4-(3-Fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)hexylidene]amino}-2-methylphthalazin-1-one

Reagents, catalysts & solvents 1

HCID 76524Titanium tetraethoxideCatalyst

Procedure

In the same way as in Example 29, 265 mg (0.86 mmol) of 4-(3-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)hexanal, 150 mg (0.86 mmol) of 5-amino-2-methylphthalazin-1-one and 0.42 ml of titanium tetraethoxide are reacted to give 5-{[4-(3-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)hexylidene]amino}-2-methylphthalazin-1-one. 410 mg of crude imine are cyclized in the same way as in Example 29 at −20° C. with 3.5 ml (3.5 mmol) of 1 M boron tribromide solution to give the desired product. Column chromatography on silica gel (hexane/ethyl acetate 50%) and subsequent preparative thin-layer chromatography on silica gel with dichloromethane/methanol 9:1 yield 10 mg of product and 8.6 mg of the 8α compound (Example 45).

Sources & evidence

ORD record
ord-881bf60f2f9846d8911d76385807814e
Source dataset
uspto-grants-2011_02
Patent number
US07880042B2

Reaction notes

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