5-Amino-2-methylphthalazin-1-one → 5-{[(2R*,4R*)-4-(3-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)pentyliden]amino}-2-methylphthalazin-1-one

HRID 1362475Notes

Reaction equation

HRID 1362475 reaction equation
[F:1][C:2]1[C:3]([O:19][CH3:20])=[C:4]([C@H:8]([CH3:18])[CH2:9][C@:10]([OH:17])([C:13]([F:16])([F:15])[F:14])[CH:11]=O)[CH:5]=[CH:6][CH:7]=1.[NH2:21][C:22]1[CH:31]=[CH:30][CH:29]=[C:28]2[C:23]=1[CH:24]=[N:25][N:26]([CH3:33])[C:27]2=[O:32]>[O-]CC.[O-]CC.[O-]CC.[O-]CC.[Ti+4]>[F:1][C:2]1[C:3]([O:19][CH3:20])=[C:4]([C@H:8]([CH3:18])[CH2:9][C@:10]([OH:17])([C:13]([F:14])([F:15])[F:16])[CH:11]=[N:21][C:22]2[CH:31]=[CH:30][CH:29]=[C:28]3[C:23]=2[CH:24]=[N:25][N:26]([CH3:33])[C:27]3=[O:32])[CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 179850455-Amino-2-methylphthalazin-1-oneHCID 25180225(2R*,4R*)-4-(3-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)pentanal

Product 1

HCID 687758605-{[(2R*,4R*)-4-(3-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)pentyliden]amino}-2-methylphthalazin-1-one

Reagents, catalysts & solvents 1

HCID 76524Titanium tetraethoxideCatalyst

Procedure

In the same way as in Example 1, 295 mg (1.0 mmol) of (2R*,4R*)-4-(3-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)pentanal, 217 mg (1.0 mmol) of 5-amino-2-methylphthalazin-1-one and 0.53 ml of titanium tetraethoxide are reacted to give 5-{[(2R*,4R*)-4-(3-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)pentyliden]amino}-2-methylphthalazin-1-one. 590 mg of resultant crude imine are cyclized, in the same way as in Example 1, at −30° C. using 10 ml (10 mmol) of 1 M boron tribromide solution to give the desired product. Column chromatography on silica gel (hexane/ethyl acetate 0-60%) yields 204 mg of product.

Sources & evidence

ORD record
ord-2f9db710d2be40d79f347281b6b8ea34
Source dataset
uspto-grants-2011_02
Patent number
US07880042B2

Reaction notes

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