5-aminoisoquinolin-1(2H)-one → 5-{[(2R,4R)-4-(4-fluoro-2-methoxy-3-methylphenyl)-2-hydroxy-2-(trifluoromethyl)hexylidene]amino}isoquinolin-1(2H)-one

HRID 1362531Notes

Reaction equation

HRID 1362531 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([CH2:18][CH3:19])[CH2:9][C@:10]([OH:17])([C:13]([F:16])([F:15])[F:14])[CH:11]=O)=[C:4]([O:20][CH3:21])[C:3]=1[CH3:22].[NH2:23][C:24]1[CH:33]=[CH:32][CH:31]=[C:30]2[C:25]=1[CH:26]=[CH:27][NH:28][C:29]2=[O:34]>CC(C)([O-])C.[Ti+4].CC(C)([O-])C.CC(C)([O-])C.CC(C)([O-])C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([CH2:18][CH3:19])[CH2:9][C@:10]([OH:17])([C:13]([F:16])([F:15])[F:14])[CH:11]=[N:23][C:24]2[CH:33]=[CH:32][CH:31]=[C:30]3[C:25]=2[CH:26]=[CH:27][NH:28][C:29]3=[O:34])=[C:4]([O:20][CH3:21])[C:3]=1[CH3:22]

Participants

4

Reactant 2

HCID 20725-aminoisoquinolin-1(2H)-oneHCID 86615331(2R,4R)-4-(4-fluoro-2-methoxy-3-methylphenyl)-2-hydroxy-2-(trifluoromethyl)hexanal

Product 1

HCID 669693265-{[(2R,4R)-4-(4-fluoro-2-methoxy-3-methylphenyl)-2-hydroxy-2-(trifluoromethyl)hexylidene]amino}isoquinolin-1(2H)-one

Reagents, catalysts & solvents 1

HCID 6451515Titanum tetra t-butoxideCatalyst

Procedure

In the same way as in Example 130, 200 mg (0.62 mmol) of (2R,4R)-4-(4-fluoro-2-methoxy-3-methylphenyl)-2-hydroxy-2-(trifluoromethyl)hexanal, 100 mg (0.62 mmol) of 5-aminoisoquinolin-1(2H)-one and 0.39 ml (1.25 mmol) of titanium tert-butoxide are reacted to give 5-{[(2R,4R)-4-(4-fluoro-2-methoxy-3-methylphenyl)-2-hydroxy-2-(trifluoromethyl)hexylidene]amino}isoquinolin-1 (2H)-one. 460 mg of crude imine are cyclized in the same way as in Example 130 at −30° C. with 7.9 ml (7.9 mmol) of 1 M boron tribromide solution to give the desired product. Column chromatography on silica gel (hexane/ethyl acetate 50-100%) yields 223 mg of desired product.

Sources & evidence

ORD record
ord-1635929b04174716bc9f3871385e7808
Source dataset
uspto-grants-2011_02
Patent number
US07880042B2

Reaction notes

Loading…