5-amino-1(2H)-phthalazinone → 5-{[(2R*,4R*)-4-(3,4-difluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)hexylidene]amino}phthalazin-1-one

HRID 1362509Notes

Reaction equation

HRID 1362509 reaction equation
[F:1][C:2]1[C:3]([O:21][CH3:22])=[C:4]([C@H:9]([CH2:19][CH3:20])[CH2:10][C@:11]([OH:18])([C:14]([F:17])([F:16])[F:15])[CH:12]=O)[CH:5]=[CH:6][C:7]=1[F:8].[NH2:23][C:24]1[CH:33]=[CH:32][CH:31]=[C:30]2[C:25]=1[CH:26]=[N:27][NH:28][C:29]2=[O:34]>CC(C)([O-])C.CC(C)([O-])C.CC(C)([O-])C.CC(C)([O-])C.[Ti+4]>[F:1][C:2]1[C:3]([O:21][CH3:22])=[C:4]([C@H:9]([CH2:19][CH3:20])[CH2:10][C@:11]([OH:18])([C:14]([F:17])([F:16])[F:15])[CH:12]=[N:23][C:24]2[CH:33]=[CH:32][CH:31]=[C:30]3[C:25]=2[CH:26]=[N:27][NH:28][C:29]3=[O:34])[CH:5]=[CH:6][C:7]=1[F:8]

Participants

4

Reactant 2

HCID 123410025-amino-1(2H)-phthalazinoneHCID 86615326(2R*,4R*)-4-(3,4-difluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)hexanal

Product 1

HCID 687743985-{[(2R*,4R*)-4-(3,4-difluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)hexylidene]amino}phthalazin-1-one

Reagents, catalysts & solvents 1

HCID 6451515Titanum tetra t-butoxideCatalyst

Procedure

In the same way as in Example 29, 372 mg (1.14 mmol) of (2R*,4R*)-4-(3,4-difluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)hexanal, 200 mg (1.14 mmol) of 5-aminophthalazin-1-one and 0.36 ml of titanium tetra-tert-butoxide are reacted to give 5-{[(2R*,4R*)-4-(3,4-difluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)hexylidene]amino}phthalazin-1-one. 560 mg of crude imine are cyclized in the same way as in Example 29 at −30° C. with 11.8 ml (11.8 mmol) of 1 M boron tribromide solution to give the desired product. Preparative thin-layer chromatography on silica gel (hexane/2-propanol 17%) yields 249 mg of the desired product

Sources & evidence

ORD record
ord-6acc239c5b0844129239d3fb89677081
Source dataset
uspto-grants-2011_02
Patent number
US07880042B2

Reaction notes

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