Acetic Acid → 4-(N-((2,4-diamino-6-pteridinyl)methyl)amino)benzoic acid

HRID 1154690Notes

Reaction equation

HRID 1154690 reaction equation
[CH:1]1[C:6](C(N[C@H](C(O)=O)CCC(O)=O)=O)=[CH:5][CH:4]=[C:3]([NH:19][CH2:20][C:21]2[CH:22]=[N:23][C:24]3[N:30]=[C:29]([NH2:31])[N:28]=[C:27]([NH2:32])[C:25]=3[N:26]=2)[CH:2]=1.[OH-].[Na+].C[C:36]([OH:38])=[O:37]>CC([O-])=O.[Na+].[Cl-].[Cl-].[Zn+2]>[CH:5]1[C:6]([C:36]([OH:38])=[O:37])=[CH:1][CH:2]=[C:3]([NH:19][CH2:20][C:21]2[N:26]=[C:25]3[C:27]([NH2:32])=[N:28][C:29]([NH2:31])=[N:30][C:24]3=[N:23][CH:22]=2)[CH:4]=1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 169371Aminopterin

Product 1

HCID 1697484-(N-((2,4-diamino-6-pteridinyl)methyl)amino)benzoic acidYield 86%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 517045Sodium AcetateSolvent

Conditions

Temperature
5 °C

Procedure

Aminopterin (2.4 g, 0.005 mol) is suspended in 1M NaOAc (500 ml) containing ZnCl2 (0.1 g), and 2N NaOH is added dropwise with stirring until a clear solution forms. Glacial AcOH is then added dropwise to bring the pH to 7.5, and 5 μl of carboxypeptidase G1 (4000 units/ml) is added. The mixture is shaken at 37° C. for 1 day, cooled to 5° C., and suction filtered. The solid is washed thoroughly with H2O, and dried in vacuo on a freeze-drying apparatus to obtain 4-amino-4-deoxypteroic acid (APA) (1.43 g, 86%) as an orange-yellow solid. The analytical sample is prepared by passing a small amount of this material through a microcrystalline cellulose column, with 0.1M glycine, pH 10, as the eluent. Appropriate fractions are pooled and acidified with AcOH, and the precipitate is collected, washed with H2O, and dried in vacuo over P2O5 ; Rf 0.1 (cellulose, pH 7.4 phosphate), dark absorbing spot; UVλmax (0.1N HCl) 243 nm (ε 18,500), 297 (23,900), 337 infl (13,700); UVλmax (0.1N NaOH) 261 nm (ε 30,400), 371 (9,100). Analysis for C, H, and N confirms the composition of APA.

Workup

  1. additionis added dropwise
  2. addition(4000 units/ml) is added
  3. stirringThe mixture is shaken at 37° C. for 1 day
  4. filtrationsuction filtered
  5. washThe solid is washed thoroughly with H2O
  6. customdried in vacuo on a freeze-drying apparatus

Sources & evidence

ORD record
ord-26775886c76d4b87810420f33ba47ed3
Source dataset
uspto-grants-1984_12
Patent number
US04490529

Reaction notes

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