5-Amino-7,8-difluoro-2-methylquinazoline → (2R*,4S*)-1-[(7,8-difluoro-2-methylquinazolin-5-yl)imino]-4-(3-fluoro-2-methoxyphenyl)-2-(trifluoromethyl)pentan-2-ol

HRID 1362479Notes

Reaction equation

HRID 1362479 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]=[C:30]([F:32])[C:29]([F:33])=[C:28]2[C:23]=1[CH:24]=[N:25][C:26]([CH3:34])=[N:27]2>[O-]CC.[O-]CC.[O-]CC.[O-]CC.[Ti+4]>[F:32][C:30]1[C:29]([F:33])=[C:28]2[C:23]([CH:24]=[N:25][C:26]([CH3:34])=[N:27]2)=[C:22]([N:21]=[CH:11][C@:10]([C:13]([F:14])([F:15])[F:16])([OH:17])[CH2:9][C@@H:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=2[O:19][CH3:20])[CH3:18])[CH:31]=1

Participants

4

Reactant 2

HCID 179891015-Amino-7,8-difluoro-2-methylquinazolineHCID 86615316(2R*,4S*)-4-(3-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)pentanal

Product 1

HCID 86615317(2R*,4S*)-1-[(7,8-difluoro-2-methylquinazolin-5-yl)imino]-4-(3-fluoro-2-methoxyphenyl)-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 (0.60 mmol) of 5-amino-7,8-difluoro-2-methylquinazoline and 0.31 ml of titanium tetraethoxide are reacted to give (2R*,4S*)-1-[(7,8-difluoro-2-methylquinazolin-5-yl)imino]-4-(3-fluoro-2-methoxyphenyl)-2-(trifluoromethyl)pentan-2-ol. 85 mg of imine purified by column chromatography (silica gel, hexane/ethyl acetate 0-30%) are cyclized in the same way as in Example 1 at −20° C. using 0.72 ml (0.72 mmol) of 1 M boron tribromide solution to give the desired product. Preparative thin-layer chromatography on silica gel (hexane/ethyl acetate 50%) yields 15 mg of product.

Sources & evidence

ORD record
ord-106e3b5921db458cad6f51d49c2b63ca
Source dataset
uspto-grants-2011_02
Patent number
US07880042B2

Reaction notes

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