Hydrochloric Acid → 6-(5-amino-2-chlorophenyl)-2-(2-(dimethylamino)ethylamino)-8-methoxypyrido[2,3-d]pyrimidin-7(8H)-one

HRID 1517245Notes

Reaction equation

HRID 1517245 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-])=O)=[CH:4][C:3]=1[C:11]1[C:26](=[O:27])[N:25]([O:28][CH3:29])[C:14]2[N:15]=[C:16]([NH:19][CH2:20][CH2:21][N:22]([CH3:24])[CH3:23])[N:17]=[CH:18][C:13]=2[CH:12]=1.Cl>CCO.[Fe]>[NH2:8][C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[C:3]([C:11]2[C:26](=[O:27])[N:25]([O:28][CH3:29])[C:14]3[N:15]=[C:16]([NH:19][CH2:20][CH2:21][N:22]([CH3:24])[CH3:23])[N:17]=[CH:18][C:13]=3[CH:12]=2)[CH:4]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 674430196-(2-chloro-5-nitrophenyl)-2-(2-(dimethylamino)ethylamino)-8-methoxypyrido[2,3-d]pyrimidin-7(8H)-one

Product 1

HCID 584783586-(5-amino-2-chlorophenyl)-2-(2-(dimethylamino)ethylamino)-8-methoxypyrido[2,3-d]pyrimidin-7(8H)-oneYield 32%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

To an solution of 6-(2-chloro-5-nitrophenyl)-2-(2-(dimethylamino)ethylamino)-8-methoxypyrido[2,3-d]pyrimidin-7(8H)-one (73.2 mmol) in EtOH (700 mL) were added conc. aq. hydrochloric acid (170 mL) and iron powder (732 mmol), and the mixture was stirred at 80° C. for 6 h. The mixture was allowed to cool to room temperature and filtered through a pad of Celite. The filtrate was diluted with EtOAc (700 mL) and washed with sat. aq. NaHCO3 (700 mL). The aqueous layer was backextracted with EtOAc (8×300 mL). The organic layers were combined and washed with sat. aq. NaCl (1×700 mL). Drying of the organic layer over Na2SO4, followed by evaporation of the solvent gave crude product that was purified by column chromatography on silica gel (dichloromethane/triethylamine 95:5, followed by dichloromethane/MeOH/triethylamine 90:5:5). The collected fractions were dissolved in dichloromethane and washed with water to remove triethylamine salts. The aqueous layer was backextracted with dichloromethane, the organic layers were combined, dried over Na2SO4, filtered and evaporated to give 6-(5-amino-2-chlorophenyl)-2-(2-(dimethylamino)ethylamino)-8-methoxypyrido[2,3-d]pyrimidin-7(8H)-one as a solid (32%).

Workup

  1. temperatureto cool to room temperature
  2. filtrationfiltered through a pad of Celite
  3. additionThe filtrate was diluted with EtOAc (700 mL)
  4. washwashed with sat. aq. NaHCO3 (700 mL)
  5. washwashed with sat. aq. NaCl (1×700 mL)
  6. dry with materialDrying of the organic layer over Na2SO4
  7. customfollowed by evaporation of the solvent
  8. customgave crude product that
  9. customwas purified by column chromatography on silica gel (dichloromethane/triethylamine 95:5, followed by dichloromethane/MeOH/triethylamine 90:5:5)
  10. dissolutionThe collected fractions were dissolved in dichloromethane
  11. washwashed with water
  12. customto remove triethylamine salts
  13. dry with materialdried over Na2SO4
  14. filtrationfiltered
  15. customevaporated

Sources & evidence

ORD record
ord-c6728ca6631a49f5a778ea784d8cd04e
Source dataset
uspto-grants-2012_07
Patent number
US08232283B2

Reaction notes

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