Hydrochloric Acid → HCID 178508845, compound

HRID 1847133Notes

Reaction equation

HRID 1847133 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 83%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
2.5 °C

Procedure

A 3 L flask equipped with magnetic stirrer, ice bath and thermometer was charged with of 1 L of water containing 15.2 g of NaOH (5 eqv.) and the solution was cooled to 0-5° C. To this solution was added 50 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 75 g of NaCl and stirred. At the beginning everything was dissolved and a clear solution was formed. The mixture was stirred at it 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 32.7 g of pemetrexed disodium 2.5 hydrate in 83% yield as a white solid with a purity of 99.4% analyzed by HPLC.

Workup

  1. customA 3 L 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 it 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-76c09199387e447eb522c00a76789eb2
Source dataset
uspto-grants-2015_02
Patent number
US08952153B2

Reaction notes

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