5-Amino-2-ethylquinazoline → 1-[(2-Ethylquinazolin-5-yl)imino]-4-(3-fluoro-2-methoxyphenyl)-2-(trifluoromethyl)hexan-2-ol

HRID 1362497Notes

Reaction equation

HRID 1362497 reaction equation
[F:1][C:2]1[C:3]([O:20][CH3:21])=[C:4]([CH:8]([CH2:18][CH3:19])[CH2:9][C:10]([OH:17])([C:13]([F:16])([F:15])[F:14])[CH:11]=O)[CH:5]=[CH:6][CH:7]=1.[NH2:22][C:23]1[CH:32]=[CH:31][CH:30]=[C:29]2[C:24]=1[CH:25]=[N:26][C:27]([CH2:33][CH3:34])=[N:28]2>[O-]CC.[O-]CC.[O-]CC.[O-]CC.[Ti+4]>[CH2:33]([C:27]1[N:26]=[CH:25][C:24]2[C:29](=[CH:30][CH:31]=[CH:32][C:23]=2[N:22]=[CH:11][C:10]([C:13]([F:14])([F:15])[F:16])([OH:17])[CH2:9][CH:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=2[O:20][CH3:21])[CH2:18][CH3:19])[N:28]=1)[CH3:34]

Participants

4

Reactant 2

HCID 669689825-Amino-2-ethylquinazolineHCID 866153234-(3-Fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)hexanal

Product 1

HCID 669694671-[(2-Ethylquinazolin-5-yl)imino]-4-(3-fluoro-2-methoxyphenyl)-2-(trifluoromethyl)hexan-2-ol

Reagents, catalysts & solvents 1

HCID 76524Titanium tetraethoxideCatalyst

Procedure

In the same way as in Example 31, 112 mg (0.37 mmol) of (4-(3-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)hexanal, 60 mg (0.37 mmol) of 5-amino-2-ethylquinazoline and 0.2 ml of titanium tetraethoxide are reacted to give 1-[(2-ethylquinazolin-5-yl)imino]-4-(3-fluoro-2-methoxyphenyl)-2-(trifluoromethyl)hexan-2-ol. 280 mg of crude imine are cyclized in the same way as in Example 31 at −20° C. with 2.4 ml (2.4 mmol) of 1 M boron tribromide solution to give the desired product. Purification by chromatography on silica gel (ethyl acetate) gives 4 mg of desired product and 11 mg of the 8α compound (Example 49).

Sources & evidence

ORD record
ord-4ff0405ee50d4963ba65f90bae1b9bd9
Source dataset
uspto-grants-2011_02
Patent number
US07880042B2

Reaction notes

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