7-Fluoro-2-methylquinazolin-5-amine → 4-(3-Fluoro-2-methoxyphenyl)-1-[(7-fluoro-2-methylquinazolin-5-yl)imino]-2-(trifluoromethyl)heptan-2-ol

HRID 1362514Notes

Reaction equation

HRID 1362514 reaction equation
[F:1][C:2]1[C:3]([O:21][CH3:22])=[C:4]([CH:8]([CH2:18][CH2:19][CH3:20])[CH2:9][C:10]([OH:17])([C:13]([F:16])([F:15])[F:14])[CH:11]=O)[CH:5]=[CH:6][CH:7]=1.[NH2:23][C:24]1[CH:33]=[C:32]([F:34])[CH:31]=[C:30]2[C:25]=1[CH:26]=[N:27][C:28]([CH3:35])=[N:29]2>[O-]CC.[O-]CC.[O-]CC.[O-]CC.[Ti+4]>[F:1][C:2]1[C:3]([O:21][CH3:22])=[C:4]([CH:8]([CH2:18][CH2:19][CH3:20])[CH2:9][C:10]([C:13]([F:16])([F:14])[F:15])([OH:17])[CH:11]=[N:23][C:24]2[CH:33]=[C:32]([F:34])[CH:31]=[C:30]3[C:25]=2[CH:26]=[N:27][C:28]([CH3:35])=[N:29]3)[CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 179850417-Fluoro-2-methylquinazolin-5-amineHCID 866153274-(3-Fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)heptanal

Product 1

HCID 669689874-(3-Fluoro-2-methoxyphenyl)-1-[(7-fluoro-2-methylquinazolin-5-yl)imino]-2-(trifluoromethyl)heptan-2-ol

Reagents, catalysts & solvents 1

HCID 76524Titanium tetraethoxideCatalyst

Procedure

In the same way as in Example 61, 228 mg (0.71 mmol) of 4-(3-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)heptanal, 150 mg (0.85 mmol) of 5-amino-7-fluoro-2-methylquinazoline and 0.5 ml of titanium tetraethoxide are reacted to give 4-(3-fluoro-2-methoxyphenyl)-1-[(7-fluoro-2-methylquinazolin-5-yl)imino]-2-(trifluoromethyl)heptan-2-ol. 185 mg of imine purified by column chromatography (silica gel, hexane/ethyl acetate 0-25%) are cyclized in the same way as in Example 61 at −20° C. with 3 ml (3 mmol) of 1 M boron tribromide solution to give the desired product. Column chromatography on silica gel (hexane/ethyl acetate 0-65%) yields 27 mg of product and 38 mg of the corresponding 5α,6α,8α) compound (Example 64).

Sources & evidence

ORD record
ord-14a0309dcbac4adcbb4ddbe389bade6c
Source dataset
uspto-grants-2011_02
Patent number
US07880042B2

Reaction notes

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