8-Fluoro-2-methylquinazolin-5-amine → (2R*,4S*)-4-(3-fluoro-2-methoxyphenyl)-1-[(8-fluoro-2-methylquinazolin-5-yl)imino]-2-(trifluoromethyl)pentan-2-ol

HRID 1362478Notes

Reaction equation

HRID 1362478 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][C:29]([F:32])=[C:28]2[C:23]=1[CH:24]=[N:25][C:26]([CH3:33])=[N:27]2>[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]([C:13]([F:14])([F:15])[F:16])([OH:17])[CH:11]=[N:21][C:22]2[CH:31]=[CH:30][C:29]([F:32])=[C:28]3[C:23]=2[CH:24]=[N:25][C:26]([CH3:33])=[N:27]3)[CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 179850558-Fluoro-2-methylquinazolin-5-amineHCID 86615316(2R*,4S*)-4-(3-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)pentanal

Product 1

HCID 68770151(2R*,4S*)-4-(3-fluoro-2-methoxyphenyl)-1-[(8-fluoro-2-methylquinazolin-5-yl)imino]-2-(trifluoromethyl)pentan-2-ol

Reagents, catalysts & solvents 1

HCID 76524Titanium tetraethoxideCatalyst

Procedure

In the same way as in Example 1, 170 mg (0.58 mmol) of (2R*,4S*)-4-(3-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)pentanal, 124 mg (0.70 mmol) of 5-amino-8-fluoro-2-methylquinazoline and 0.31 ml of titanium tetraethoxide are reacted to give (2R*,4S*)-4-(3-fluoro-2-methoxyphenyl)-1-[(8-fluoro-2-methylquinazolin-5-yl)imino]-2-(trifluoromethyl)pentan-2-ol. 295 mg of resultant crude imine are cyclized in the same way as in Example 1 at −20° C. using 2.6 ml (2.6 mmol) of 1 M boron tribromide solution to give the desired product. Column chromatography on silica gel (hexane/ethyl acetate 50%) yields 25 mg of product.

Sources & evidence

ORD record
ord-3c21847925964898987477b8a81fc781
Source dataset
uspto-grants-2011_02
Patent number
US07880042B2

Reaction notes

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