Cyanogen Bromide → Quinazolin-2-amine

反応式

[CH:1]1[C:6]2[N:7]=[C:8]3[N:13]([CH2:14][C:5]=2[C:4](Cl)=[C:3](Cl)[CH:2]=1)CC(=O)[NH:9]3.O.Cl.C(N(CC1C(N)=CC=C(Cl)C=1Cl)CC(O)=O)C.N#CBr>>[NH:9]=[C:8]1[N:13]=[CH:14][C:5]2[C:6](=[CH:1][CH:2]=[CH:3][CH:4]=2)[NH:7]1

参加物

反応物 4

HCID 10476Cyanogen Bromide2 回

HCID 21885828Hydrate;hydrochloride2 回

HCID 67080112ethyl-N-(6-amino-2,3-dichlorobenzyl)glycine2 回

HCID 135409400Anagrelide

生成物 1

HCID 178508286Quinazolin-2-amine

実験手順

Commercially, as discussed in U.S. Pat. No. 5,801,245 and as shown in FIG. 1, Anagrelide has been prepared as the hydrochloride monohydrate (compound IV) from the intermediate, ethyl N-(6-amino-2,3-dichlorobenzyl)glycine (compound I) by reaction with cyanogen bromide in hot alcohol solution, or, preferentially, by reaction with cyanogen bromide in an aprotic solvent to give the iminoquinazoline intermediate (compound II) which is isolated and then reacted with a base in a hot solution of alcohol to form Anagrelide base (compound III).