Hydrochloric Acid → Anagrelide

HRID 275005Notes

Reaction equation

HRID 275005 reaction equation
Cl.C(N=[C:5]1[N:14]([CH2:15][C:16]#[N:17])[CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[C:10]([Cl:19])[C:11]=2[Cl:18])[NH:6]1)#N.C(=O)([O-])[O-:21].[K+].[K+]>C(O)CO>[Cl:18][C:11]1[C:10]([Cl:19])=[CH:9][CH:8]=[C:7]2[C:12]=1[CH2:13][N:14]1[CH2:15][C:16](=[O:21])[NH:17][C:5]1=[N:6]2

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 178511313(2-Cyanoimino-5,6-dichloro-1,2,3,4-tetrahydroquinazolin-3-yl) acetonitrile

Product 1

HCID 135409400AnagrelideYield 97.1%

Reagents, catalysts & solvents 1

HCID 174Ethylene GlycolSolvent

Procedure

To a mixture of 15 ml of ethylene glycol and 2 ml (0.02 moles) of cc. hydrochloric acid, warmed to 120° C., 2.50 g (0.01 mole) of (2-cyanoimino-5,6-dichloro-1,2,3,4-tetrahydroquinazolin-3-yl) acetonitrile are added, and the solution is stirred at the same temperature for 20 minutes. Then it is cooled to room temperature and made neutral with 10% potassium carbonate solution. The separated crystals are filtered off. Thus 2.72 g (97.1%) of crude 6,7-dichloro-1,5dihydroimidazo[2,1-b]quinazolin-2[3H]-one base are obtained (m.p.>300° C., HPLC content: 97.2%), which is dissolved in a hot mixture of 15 ml of methanol and 16 ml of cc. ethanolic hydrogen chloride (hydrogen chloride content: 0.76 moles/1000 ml) and allowed to crystallize. Then it is cooled, the separated product is filtered off and washed with a slight amount of ethanol.

Workup

  1. filtrationThe separated crystals are filtered off

Sources & evidence

ORD record
ord-b9fa29e2df60453db47f9da4b6a4979c
Source dataset
uspto-grants-1995_02
Patent number
US05391737

Reaction notes

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