Hydrochloric Acid → HCID 178508845, compound

HRID 1847132Notes

Reaction equation

HRID 1847132 reaction equation
[OH-:1].[Na+:2].C1(C)C=CC(S(O)(=O)=[O:10])=CC=1.C([O:16][C:17](=[O:48])[C@H:18]([CH2:41][CH2:42][C:43]([O:45]CC)=[O:44])[NH:19][C:20](=[O:40])[C:21]1[CH:26]=[CH:25][C:24]([CH2:27][CH2:28][C:29]2[C:37]3[C:36](=[O:38])[NH:35][C:34]([NH2:39])=[N:33][C:32]=3[NH:31][CH:30]=2)=[CH:23][CH:22]=1)C.Cl.[Na+].[Cl-]>O>[CH:23]1[C:24]([CH2:27][CH2:28][C:29]2[C:37]3[C:36]([N:35]=[C:34]([NH2:39])[NH:33][C:32]=3[NH:31][CH:30]=2)=[O:38])=[CH:25][CH:26]=[C:21]([C:20]([NH:19][C@H:18]([C:17]([O-:48])=[O:16])[CH2:41][CH2:42][C:43]([O-:45])=[O:44])=[O:40])[CH:22]=1.[CH:23]1[C:24]([CH2:27][CH2:28][C:29]2[C:37]3[C:36]([N:35]=[C:34]([NH2:39])[NH:33][C:32]=3[NH:31][CH:30]=2)=[O:38])=[CH:25][CH:26]=[C:21]([C:20]([NH:19][C@H:18]([C:17]([O-:48])=[O:16])[CH2:41][CH2:42][C:43]([O-:45])=[O:44])=[O:40])[CH:22]=1.[OH2:10].[OH2:1].[OH2:10].[OH2:10].[OH2:10].[Na+:2].[Na+:2].[Na+:2].[Na+:2]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 5234Sodium ChlorideHCID 14798Sodium HydroxideHCID 135741210L-Glutamic acid, N-[4-[2-(2-amino-4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-, 1,5-diethyl ester, 4-methylbenzenesulfonate (1:1)

Product 1

HCID 178508845HCID 178508845, compoundYield 81%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
2.5 °C

Procedure

A 500 mL flask equipped with magnetic stirrer, ice bath and thermometer was charged with 95 mL of water containing 1.52 g of NaOH (5 eqv.) and the solution was cooled to 0-5° C. To this solution was added 5 g of N-[4-[2-(2-Amino-4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid diethylester p-toluenesulfonic acid salt. The mixture was stirred at 0-5° C. for 30-35 minutes. The pH was adjusted to 7-9 by adding 1N HCl. The mixture was warmed to rt. To the solution was added 10 gr of NaCl and stirred. At the beginning everything was dissolved and a clear solution was formed. The mixture was stirred at rt for 50-60 minutes and pemetrexed disodium was precipitated. The solid was isolated by filtration and washed with 10 ml of ethanol/water (7/2 v/v). The solid was dried in a vacuum oven at 50-55° C. for 5-6 hours to give 3.19 g of pemetrexed disodium 2.5 hydrate in 81% yield as a white solid with a purity of 99.5% analyzed by HPLC.

Workup

  1. customA 500 mL flask equipped with magnetic stirrer, ice bath
  2. temperatureThe mixture was warmed to rt
  3. stirringstirred
  4. dissolutionAt the beginning everything was dissolved
  5. customa clear solution was formed
  6. stirringThe mixture was stirred at rt for 50-60 minutes
  7. custompemetrexed disodium was precipitated
  8. customThe solid was isolated by filtration
  9. washwashed with 10 ml of ethanol/water (7/2 v/v)
  10. customThe solid was dried in a vacuum oven at 50-55° C. for 5-6 hours

Sources & evidence

ORD record
ord-f3e09116049e4828a35267392dfc36b5
Source dataset
uspto-grants-2015_02
Patent number
US08952153B2

Reaction notes

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