5-amino-7-fluoroquinolin-2(1H)-one → HCID 91409687, compound

HRID 1362535Notes

Reaction equation

HRID 1362535 reaction equation
[CH2:1]([C:3]1[C:4]([O:22][CH3:23])=[C:5]([CH:10]([CH2:20][CH3:21])[CH2:11][C@:12]([OH:19])([C:15]([F:18])([F:17])[F:16])[CH:13]=O)[CH:6]=[CH:7][C:8]=1[F:9])[CH3:2].[NH2:24][C:25]1[CH:34]=[C:33]([F:35])[CH:32]=[C:31]2[C:26]=1[CH:27]=[CH:28][C:29](=[O:36])[NH:30]2>CC(C)([O-])C.[Ti+4].CC(C)([O-])C.CC(C)([O-])C.CC(C)([O-])C>[CH2:1]([C:3]1[C:4]([O:22][CH3:23])=[C:5]([CH:10]([CH2:20][CH3:21])[CH2:11][C@:12]([OH:19])([C:15]([F:17])([F:16])[F:18])[CH:13]=[N:24][C:25]2[CH:34]=[C:33]([F:35])[CH:32]=[C:31]3[C:26]=2[CH:27]=[CH:28][C:29](=[O:36])[NH:30]3)[CH:6]=[CH:7][C:8]=1[F:9])[CH3:2]

Participants

4

Reactant 2

HCID 669694385-amino-7-fluoroquinolin-2(1H)-oneHCID 87708536HCID 87708536, compound

Product 1

HCID 91409687HCID 91409687, compound

Reagents, catalysts & solvents 1

HCID 6451515Titanum tetra t-butoxideCatalyst

Procedure

In the same way as in Example 137, 45 mg (0.13 mmol) of (2R,4R/S)-4-(3-ethyl-4-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)hexanal, 23 mg (0.13 mmol) of 5-amino-7-fluoroquinolin-2(1H)-one and 0.09 ml (0.27 mmol) of titanium tert-butoxide are reacted to give 5-{[(2R,4R/S)-4-(3-ethyl-4-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)hexylidene]amino}-7-fluoroquinolin-2(1H)-one. 80 mg of crude imine are cyclized in the same way as in Example 137 at −30° C. with 1.3 ml (1.3 mmol) of 1 M boron tribromide solution. Purification by column chromatography on silica gel (hexane/isopropanol 16%) and subsequent preparative thin-layer chromatography on an amine phase (Merck NH2F254, ethyl acetate/triethylamine, 2%) yield 7 mg of the title compound and 5 mg of the corresponding (8R)-diastereomer.

Sources & evidence

ORD record
ord-3a72be47eabc4f81b4445b7576236044
Source dataset
uspto-grants-2011_02
Patent number
US07880042B2

Reaction notes

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