Citric Acid → N-[4-[4-(2,4-diamino-6-methyl-5-pyrimidinyl)-1-piperazinyl]benzoyl]-L-glutamic acid

HRID 371457

Reaction equation

HRID 371457 reaction equation
C([O:3][C:4](=[O:37])[C@H:5]([CH2:30][CH2:31][C:32]([O:34]CC)=[O:33])[NH:6][C:7](=[O:29])[C:8]1[CH:13]=[CH:12][C:11]([N:14]2[CH2:19][CH2:18][N:17]([C:20]3[C:21]([NH2:28])=[N:22][C:23]([NH2:27])=[N:24][C:25]=3[CH3:26])[CH2:16][CH2:15]2)=[CH:10][CH:9]=1)C.[OH-].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CO>[NH2:27][C:23]1[N:22]=[C:21]([NH2:28])[C:20]([N:17]2[CH2:16][CH2:15][N:14]([C:11]3[CH:10]=[CH:9][C:8]([C:7]([NH:6][C@H:5]([C:4]([OH:37])=[O:3])[CH2:30][CH2:31][C:32]([OH:34])=[O:33])=[O:29])=[CH:13][CH:12]=3)[CH2:19][CH2:18]2)=[C:25]([CH3:26])[N:24]=1

Participants

5

Reactant 3

HCID 311Citric AcidHCID 14798Sodium HydroxideHCID 13478337N-[4-[4-(2,4-Diamino-6-methyl-5-pyrimidinyl)-1-piperazinyl]benzoyl]-L-glutamic acid diethyl ester

Product 1

HCID 13478336N-[4-[4-(2,4-diamino-6-methyl-5-pyrimidinyl)-1-piperazinyl]benzoyl]-L-glutamic acidYield 28.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 3.00 g (0.0058 mole) of N-[4-[4-(2,4-diamino-6-methyl-5-pyrimidinyl)-1-piperazinyl]-benzoyl]-L-glutamic acid diethyl ester and 12.5 ml of 1N aqueous sodium hydroxide solution in 150 ml of methanol was stirred at room temperature for four hours. The methanol was removed under vacuum at 23° C. and the residue was dissolved in 100 ml of ice water and then neutralized by the addition of 2.5 g (0.0129 moles) of citric acid. The solid precipitate was collected, washed with water, and then triturated several times with ethanol. The remaining solid was dried overnight in vacuo at 67° C. to give 0.75 g of the product as a white powder, mp 270° C. (dec.).

Workup

  1. customThe methanol was removed under vacuum at 23° C.
  2. dissolutionthe residue was dissolved in 100 ml of ice water
  3. customThe solid precipitate was collected
  4. washwashed with water
  5. customtriturated several times with ethanol
  6. customThe remaining solid was dried overnight in vacuo at 67° C.

Sources & evidence

ORD record
ord-b329b7b11ee34d3c9679794b347d968c
Source dataset
uspto-grants-1985_07
Patent number
US04532240

Linked notes

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