Carbon Disulfide → HCID 178518761, compound
Reaction equation
[C:1]([NH2:10])(=[O:9])[C:2]1[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[NH2:4].[OH-].[K+].[C:13](=S)=[S:14]>>[SH:14][C:13]1[NH:10][C:1](=[O:9])[C:2]2[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:4]=1Participants
Procedure
Aminoalcohol VIII was then allowed to react with 2,4-dimethylthioquinazoline (IX) in acetonitrile at reflux to give 4-[(3-(4-methoxyphenyl)piperazine-1-yl)propan-2-ol-1-yl]amino-2-methylthioquinazoline (XI). But the results were variable in the yields ranging from 24 to 56% and the reaction released notorious methylthiol. The possibility of synthesizing compound XI by using 4-chloro-2-methylthioquinazoline (X) was also investigated. Compound X was obtained in good yield (90-93%) starting from anthranilamide by heating with carbon disulfide in water-alcohol solution of potassium hydroxide to afford 2-mercaptoquinazolin-4-one (XII) in 91% yield. (Zakerinia, M. et. al. Helv. Chim. Acta. 1990, 73, 912-915) Compound XII was then methylated with methyl iodide to give 2-methylthioquinazolin-2-one (XIII) which was subsequently converted to 4-chloro-2-methylthioquinazoline (X) in high yield (90-93%) by treating with POCl3, followed by precipitation with water from acetone solution. Compound X was reacted smoothly with amino alcohol VIII in the presence of triethylamine to give compound XI in 72% yield. The cyclization of XI to compound I was achieved by methanesulphonylchloride (MsCl) and triethylamine. The cyclization reaction proceeded in 12-17 hours to give compound I with 47-69% chemical yield after chromatographical purification. The addition of potassium carbonate to the reaction mixture to trap hydrogen chloride formed allowed to obtain a chromatographically pure compound I in 77% yield without column chromatography. ##STR7##
Workup
- customin good yield (90-93%)
Sources & evidence
- ORD record
- ord-b46e4da2121e4093a3ac3d9469a19c6a
- Source dataset
- uspto-grants-1999_08
- Patent number
- US05932584
Reaction notes
Loading…