Ethylene Glycol → Anagrelide
Reaction equation
Cl.C(O[N:6]1[CH2:15][C:14]2[C:9](=[CH:10][CH:11]=[C:12]([Cl:17])[C:13]=2[Cl:16])[N:8](CC)[C:7]1=[N:20]C#N)(=O)C.C(=O)([O-])[O-].[K+].[K+].[CH2:29]([OH:32])[CH2:30]O>>[Cl:16][C:13]1[C:12]([Cl:17])=[CH:11][CH:10]=[C:9]2[C:14]=1[CH2:15][N:6]1[CH2:30][C:29](=[O:32])[NH:20][C:7]1=[N:8]2Participants
Procedure
To a solution of 150 ml of ethylene glycol and 15 ml (0.15 moles) of cc. hydrochloric acid 24.5 g (0.075 moles) of ethyl-(2-cyanoimino-5,6-dichloro-1,2,3,4-tetrahydroquinazolin-3-yl) acetate are added in small portions, within about 10 minutes, at 115° C., and the mixture is kept at the same temperature for further 20 minutes. Then it is cooled to room temperature and made neutral by the dropwise addition of 10% potassium carbonate solution. The separated crystals are filtered off. Thus 17.75 g (93.0%) of 6,7-dichloro-1,5-dihydroimidazo[2,1-b]quinazolin-2[3H]-one base are obtained (m.p.>300° C., HPLC content: 99.5%), which is dissolved in a hot mixture of 150 ml of methanol and 150 ml of cc. ethanolic hydrogen chloride (hydrogen chloride content: 0.75 moles/1000 ml). The mixture is then cooled, the separated product is filtered off and washed with a slight amount of ethanol.
Workup
- filtrationThe separated crystals are filtered off
Sources & evidence
- ORD record
- ord-c737283169824774b8af892460ff65c4
- Source dataset
- uspto-grants-1995_02
- Patent number
- US05391737
Reaction notes
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