5-amino-8-fluoroquinolin-2(1H)-one → 8-fluoro-5-{[(2R,4R)-4-(4-fluoro-2-methoxy-3-methylphenyl)-2-hydroxy-2-(trifluoromethyl)hexylidene]amino}quinolin-2(1H)-one

HRID 1362530Notes

Reaction equation

HRID 1362530 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][C:31]([F:34])=[C:30]2[C:25]=1[CH:26]=[CH:27][C:28](=[O:35])[NH:29]2>CC(C)([O-])C.[Ti+4].CC(C)([O-])C.CC(C)([O-])C.CC(C)([O-])C>[F:34][C:31]1[CH:32]=[CH:33][C:24]([N:23]=[CH:11][C@@:10]([OH:17])([C:13]([F:16])([F:14])[F:15])[CH2:9][C@H:8]([C:5]2[CH:6]=[CH:7][C:2]([F:1])=[C:3]([CH3:22])[C:4]=2[O:20][CH3:21])[CH2:18][CH3:19])=[C:25]2[C:30]=1[NH:29][C:28](=[O:35])[CH:27]=[CH:26]2

Participants

4

Reactant 2

HCID 179891895-amino-8-fluoroquinolin-2(1H)-oneHCID 86615331(2R,4R)-4-(4-fluoro-2-methoxy-3-methylphenyl)-2-hydroxy-2-(trifluoromethyl)hexanal

Product 1

HCID 669696848-fluoro-5-{[(2R,4R)-4-(4-fluoro-2-methoxy-3-methylphenyl)-2-hydroxy-2-(trifluoromethyl)hexylidene]amino}quinolin-2(1H)-one

Reagents, catalysts & solvents 1

HCID 6451515Titanum tetra t-butoxideCatalyst

Procedure

In the same way as in Example 130, 300 mg (0.93 mmol) of (2R,4R)-4-(4-fluoro-2-methoxy-3-methylphenyl)-2-hydroxy-2-(trifluoromethyl)hexanal, 165 mg (0.93 mmol) of 5-amino-8-fluoroquinolin-2(1H)-one and 0.58 ml of titanium tert-butoxide are reacted to give 8-fluoro-5-{[(2R,4R)-4-(4-fluoro-2-methoxy-3-methylphenyl)-2-hydroxy-2-(trifluoromethyl)hexylidene]amino}quinolin-2(1H)-one. 280 mg of chromatographically purified imine (silica gel, hexane/ethyl acetate 0-75%) are cyclized in the same way as in Example 130 at −30° C. with 4.6 ml (4.6 mmol) of 1 M boron tribromide solution to give the desired product. Column chromatography on silica gel (hexane/ethyl acetate 0-100%) yields 230 mg of desired product.

Sources & evidence

ORD record
ord-6da198a8a3c241d48ca96f8e51e6e539
Source dataset
uspto-grants-2011_02
Patent number
US07880042B2

Reaction notes

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