8-Fluoro-2-methylquinazolin-5-amine → HCID 68774998, compound

HRID 1362496Notes

Reaction equation

HRID 1362496 reaction equation
[F:1][C:2]1[C:3]([O:20][CH3:21])=[C:4]([C@H: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][C:30]([F:33])=[C:29]2[C:24]=1[CH:25]=[N:26][C:27]([CH3:34])=[N:28]2>[O-]CC.[O-]CC.[O-]CC.[O-]CC.[Ti+4]>[F:1][C:2]1[C:3]([O:20][CH3:21])=[C:4]([C@@H:8]([CH2:18][CH3:19])[CH2:9][C@@:10]([C:13]([F:14])([F:15])[F:16])([OH:17])[CH:11]=[N:22][C:23]2[CH:32]=[CH:31][C:30]([F:33])=[C:29]3[C:24]=2[CH:25]=[N:26][C:27]([CH3:34])=[N:28]3)[CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 179850558-Fluoro-2-methylquinazolin-5-amineHCID 86615322HCID 86615322, compound

Product 1

HCID 68774998HCID 68774998, compound

Reagents, catalysts & solvents 1

HCID 76524Titanium tetraethoxideCatalyst

Procedure

In the same way as in Example 31, 123 mg (0.40 mmol) of (2R*,4R*)-4-(3-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)hexanal, 72 mg (0.60 mmol) of 5-amino-8-fluoro-2-methylquinazoline and 0.22 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)hexan-2-ol. 170 mg of crude imine are cyclized in the same way as in Example 31 at −30° C. with 2.8 ml (2.8 mmol) of 1 M boron tribromide solution to give the desired product. Purification by chromatography on silica gel (dichloromethane/ethyl acetate 0-40%) gives 68 mg of product.

Sources & evidence

ORD record
ord-61a80d1963664eb3a612e11b0abfedeb
Source dataset
uspto-grants-2011_02
Patent number
US07880042B2

Reaction notes

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