HCID 59465209, compound → HCID 25158767, compound

HRID 1714841Notes

Reaction equation

HRID 1714841 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([N:8]([CH2:14][C:15]2[C:20]([CH3:21])=[C:19]([O:22][CH3:23])[C:18]([CH3:24])=[CH:17][N:16]=2)[CH2:9][C:10](OC)=[O:11])[C:5]([N+:25]([O-])=O)=[C:4]([Cl:28])[N:3]=1>C(O)(=O)C.[Fe]>[NH2:1][C:2]1[N:3]=[C:4]([Cl:28])[C:5]2[NH:25][C:10](=[O:11])[CH2:9][N:8]([CH2:14][C:15]3[C:20]([CH3:21])=[C:19]([O:22][CH3:23])[C:18]([CH3:24])=[CH:17][N:16]=3)[C:6]=2[N:7]=1

Participants

4

Reactant 1

HCID 59465209HCID 59465209, compound2×

Product 1

HCID 25158767HCID 25158767, compoundYield 7.6%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 176Acetic AcidSolvent

Conditions

Temperature
65 °C

Procedure

Methyl 2-[(2-amino-6-chloro-5-nitro-pyrimidin-4-yl)-[(4-methoxy-3,5-dimethyl-pyridin-2-yl)methyl]amino]acetate (Intermediate 25)(2.0 g) was dissolved in acetic acid (120 mL) and warmed to 65° C. Iron powder (5 g) was added and the mix heated at 85° C. for 40 minutes. The reaction mixture allowed to cool, filtered and the filtrate was evaporated to dryness. The residue was purified by flash chromatography on silica, eluting with increasingly polar mixtures of methanol DCM (1/99-10/90) to give crude product. The crude product was triturated with methanol (3 mL) and the resulting solid filtered off then redissolved in 5N aqueous HCl (5 mL) and heated at 80° C. for 30 minutes. The reaction mixture was cooled, evaporated to dryness and the residue triturated with aqueous ammonia solution (d=0.880). The resulting solid was filtered off to give the title compound (129 mg) as a beige coloured solid; 1H NMR spectrum (400 MHz, DMSO) 2.20 (6H, s), 3.74 (3H, s), 4.05 (2H, s), 4.79 (2H, s), 6.17 (2H, s), 8.15 (1H, s), 9.92 (1H, s);

Workup

  1. temperaturethe mix heated at 85° C. for 40 minutes
  2. temperatureto cool
  3. filtrationfiltered
  4. customthe filtrate was evaporated to dryness
  5. customThe residue was purified by flash chromatography on silica
  6. washeluting
  7. temperaturewith increasingly polar mixtures of methanol DCM (1/99-10/90)
  8. customto give crude product
  9. customThe crude product was triturated with methanol (3 mL)
  10. filtrationthe resulting solid filtered off
  11. dissolutionthen redissolved in 5N aqueous HCl (5 mL)
  12. temperatureheated at 80° C. for 30 minutes
  13. temperatureThe reaction mixture was cooled
  14. customevaporated to dryness
  15. customthe residue triturated with aqueous ammonia solution (d=0.880)
  16. filtrationThe resulting solid was filtered off

Sources & evidence

ORD record
ord-70de04b6c686481bbabc483220271b80
Source dataset
uspto-grants-2010_09
Patent number
US07799781B2

Reaction notes

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