Deferiprone → HCID 18637992, compound

HRID 1165176Notes

Reaction equation

HRID 1165176 reaction equation
[CH3:1][N:2]1[CH:7]=[CH:6][C:5](=[O:8])[C:4]([OH:9])=[C:3]1[CH3:10].Cl.[CH3:12][O:13][C:14](=[O:23])[C@@H:15]1[CH2:19][CH2:18][CH2:17][N:16]1[C:20](Cl)=[O:21].Cl.COC(=O)[C@@H]1CCCN1.C(Cl)(Cl)=O>N1C=CC=CC=1.C(#N)C.C1(C)C=CC=CC=1.C(N(CC)CC)C>[CH3:1][N:2]1[CH:7]=[CH:6][C:5](=[O:8])[C:4]([O:9][C:20]([N:16]2[CH2:17][CH2:18][CH2:19][C@H:15]2[C:14]([O:13][CH3:12])=[O:23])=[O:21])=[C:3]1[CH3:10]

Participants

9

Reactant 4

HCID 2972DeferiproneHCID 6371PhosgeneHCID 2733200methyl L-prolinate hydrochlorideHCID 86743804HCID 86743804, compound

Product 1

HCID 18637992HCID 18637992, compound

Reagents, catalysts & solvents 4

HCID 1049PyridineSolventHCID 1140TolueneSolvent2×HCID 6342AcetonitrileSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
110 °C

Procedure

2.80 ml of triethylamine are added to a suspension of 2.78 g of 1,2-dimethyl-3-hydroxy-4(1H)-pyridinone in 100 ml of pyridine and 100 ml of acetonitrile, and then a hot solution of 1-chlorocarbonyl-L-proline methyl ester hydrochloride (prepared by reacting a solution of 0.99 g of L-proline methyl ester hydrochloride (dry) in 150 ml of toluene with 245 ml of a 20% solution of phosgene in toluene after stirring for 6 hours at 110° C.) is added dropwise. The reaction mixture becomes reddish in hue and a solution forms, whereupon a precipitate forms again immediately. After a reaction time of 20 hours the solid is removed by filtration and the filtrate is concentrated by evaporation under reduced pressure. The residue, which contains the desired product in the form of the hydrochloride, is dissolved in 50 ml of water. The solution is adjusted to pH 2.5 by addition of phosphoric acid and extracted with methylene chloride. The aqueous phase is subsequently saturated with sodium chloride and extracted once more with methylene chloride. The residue of the second extract is crystallised from 10 ml of isopropanol and 50 ml of ethyl acetate at 4° C., affording 1,2-dimethyl-3-[(2(S)-methoxycarbonylpyrrolidino)carbonyloxy]-4(1H)-pyridinone which melts at 198°-200° C.

Workup

  1. additionis added dropwise
  2. customAfter a reaction time of 20 hours the solid is removed by filtration
  3. concentrationthe filtrate is concentrated by evaporation under reduced pressure
  4. dissolutionis dissolved in 50 ml of water
  5. additionThe solution is adjusted to pH 2.5 by addition of phosphoric acid
  6. extractionextracted with methylene chloride
  7. extractionextracted once more with methylene chloride
  8. extractionThe residue of the second extract
  9. customis crystallised from 10 ml of isopropanol and 50 ml of ethyl acetate at 4° C.

Sources & evidence

ORD record
ord-a7f228b3f4a04ef6b934de7d7ef35567
Source dataset
uspto-grants-1990_03
Patent number
US04908371

Reaction notes

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